google搜索gut bacteria psoriasis

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腸的結構：

根據【9】

大約8-9米長，所以指望飲食或者藥物快速治愈銀屑病是不可能的。

因為一口下去，能覆蓋這個腸是不太可能的。

需要相當長的時間來治愈。

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腸道毒素類型

毒素類型	腸道細菌	毒素的化學形式
內毒素	革蘭氏陰性菌[11]	LPS(脂多糖)
外毒素	革蘭氏陽性菌和少數革蘭氏陰性菌[11]	腸毒素、神經毒素、細胞毒素[10]

【12】滅活乳酸菌可以去除食品中的黃曲霉毒素

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[1]中提到生酮飲食降低LPS水平，我們可以聯想到之前網絡中流行的觀點：“生酮飲食治愈銀屑病”，而LPS也與銀屑病息息相關。

【2】中提到：

• ①大鼠食用高FODMAP飲食（HFM），可增加糞便中的革蘭氏陰性菌，提高脂多糖（LPS）的濃度，引起腸道炎癥、屏障功能障礙、內臟高敏感性（VH）；
• ②抗生素處理可抑制上述癥狀，低FODMAP飲食（LFM）可逆轉上述癥狀；
• ③給大鼠結腸內灌注LPS、腸易激綜合征（IBS）患者或HFM大鼠的糞便上清，可造成腸道屏障功能障礙及VH，用LPS拮抗劑治療或敲除TLR4可抑制病癥；
• ④IBS患者的糞便LPS高于健康人，LFM處理4周顯著改善IBS患者的癥狀并降低糞便LPS水平。

【3】

脂多糖（LPS）是革蘭氏陰性細菌的主要成分，緊密結合到其細胞壁的最外層。因為其糖部分是水溶性的，而其脂質部分是脂溶性，所以LPS是兩親性物質，可溶于水和脂。

?

脂多糖的生物學作用

LPS在細菌正常生活狀態時不釋放，卻通常在細菌菌體死亡破裂、人工方法裂解后或細胞活躍生長繁殖時會釋放出來，其本身無毒性作用，但作為非特異性免疫原，當進入微循環后與宿主效應細胞（主要為單核細胞、巨噬細胞和中性粒細胞）相互作用分泌腫瘤壞死因子-α（TNF-α）、白細胞介素1（IL-1）、白細胞介素2（IL-2）、白細胞介素6（lL-6）、活性氧自由基（ROS）、一氧化碳（NO）等生物活性分子，引起機體發熱、彌散性血管內凝血、多器官機能衰竭及休克等臨床綜合癥。

LPS的毒性是通過LPS在細菌周圍形成一層保護屏障以逃避抗生素的作用，作用于宿主細胞，產生炎性細胞因子，使機體內環境處于紊亂狀態，引起內毒素血癥、膿毒癥等疾病。

LPS的活性

LPS具有廣泛的生物學活性，不僅能激活T淋巴細胞、B淋巴細胞 、巨噬細胞 、自然殺傷細胞等免疫細胞，還能促進細胞因子生成，活化補體，對免疫系統發揮多方面的調節功能；LPS還具有免疫激活作用，能抗感染、抗輻射，增加機體免疫力，保護造血組織，并具有促白細胞增生的作用。

脂多糖水平升高的主要原因?

酒精攝入量

營養不良

高脂飲食或高碳水化合物飲食

免疫細胞正在被激活（很可能是T細胞激活）

感染

腸漏

凝集素

暴飲暴食

社會隔離

吸煙

壓力

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1) Fatigue
Fatigue is reliably caused in humans by the administration of LPS, as part of LPS-induced “sickness behavior” [1].（LPS會增加疲勞與炎癥）

1) Fatigue
Fatigue is reliably caused in humans by the administration of LPS, as part of LPS-induced “sickness behavior” [1].（在一項針對39名參與者的試驗中，注射LPS增加了社交脫節、抑郁和炎癥（IL-6、TNF-a）的感覺[10]。

注射LPS后，動物海馬中TNF-α的產生增加）

17) Cancer
Higher LPS levels were associated with an increased incidence of colorectal tumors in a study of 462 adults [38].（高水平的LPS更容易誘發癌癥）

18) Alzheimer’s Disease
High levels of LPS and inflammatory cytokines were associated with Alzheimer’s disease in a study of 69 patients [40].（高水平的LPS與阿爾茨海默癥相關）

22) Retinal Disease
Pigment cells of the retina died due to exposure to LPS-induced inflammatory cytokines (IL-6 and IL-8) [45].（高水平LPS容易導致視網膜色素細胞死亡）

1) Prebiotics
In three clinical trials of 119 obese and diabetic patients, inulin/oligofructose consumed daily for 8 to 12 weeks lowered LPS levels and inflammation, and increased bifidobacteria (beneficial gut bacteria) and blood sugar control [48, 49, 50].

Resistant starch lowered LPS, oxidative stress, and insulin resistance in another trial of 56 women with type 2 diabetes [51].

Inulin-like fructans increased Bifidobacterium levels, which was associated with lower LPS levels in a trial on 30 obese women [52].

2) Probiotics
In a trial on 30 patients with cirrhosis (liver damage), Lactobacillus GG taken for 8 weeks lowered LPS and TNF-alpha levels [53].

In another trial of 30 triathletes, daily supplementation of 30 billion CFU Lactobacillus and Bifidobacterium strains for 12 weeks reduced LPS pre-race and six days post-race [54].

In a trial on 44 HIV patients, 12-week treatment with Saccharomyces boulardii reduced LPS and systemic inflammation (IL-6) [55].

In a trial on 50 women given probiotics and a Japanese herbal medicine (Bofutsushosan), increased gut levels of the probiotic Bifidobacterium breve were linked to lower levels of LPS [56].

B. infantis 35624 reduced TNF-alpha and IL-6 production caused by LPS in a trial of 22 healthy participants [57].

Both pre- and probiotic supplementation has been linked with lower LPS levels, but larger trials are needed.
3) Polyphenols
Grape extract rich in polyphenols lowered blood LPS in a study of 29 adults [58].

In a study of 10 healthy people, consumption of a resveratrol and grape polyphenol drink suppressed the LPS, oxidative stress, and inflammatory stress response to a high-fat, high-carbohydrate meal [59].

In mice, a polyphenol-rich cranberry extract reduced LPS response to a high-fat meal [60].

4) Red Wine
Red wine consumption for 20 days increased Bifidobacterium and Prevotella bacteria levels, which were associated with reduced LPS levels in a study of 10 men [61].

Red wine polyphenols decreased LPS producing-bacteria and increased the number of fecal Bifidobacterium and Lactobacillus (gut barrier protectors) and butyrate-producing bacteria in a trial of 20 individuals [62].

Remember that the potential health effects of red wine may be outweighed by the multiple risks of alcohol, especially if consumed in high amounts.

5) Omega-3 Fatty Acids
High-dose omega-3 supplementation (3.6 g/day) reduced fever and moderately lowered inflammatory cytokines due to LPS administration in a trial of 60 healthy people [63].

Omega-3 supplementation (2.5 g/day) lowered LPS-stimulated IL-6 production and anxiety symptoms in another trial of 68 participants [64].

In mice, omega 3 supplementation and omega-6 reduction increased the production of alkaline phosphatase, caused favorable changes in gut bacteria composition, and lowered LPS production, gut permeability, and inflammation [65].

6) Olive Oil
A high-phenol olive oil breakfast limited the increases in LPS and inflammatory cytokines (NF-κB, IL-6, IL-1b, and CXCL1) in a clinical trial on 49 people with metabolic syndrome [66].

In a study of 28 healthy and obese people, consumption of a diet high in palmitic acid for 3 weeks increased blood TNF-a levels caused by LPS. However, consumption of a high-oleic acid (the main fat in olive oil) diet for 3 weeks lowered LPS-induced IL-1b, IL-18, IL-10, and TNF-a [67].

7) Orange Juice
When consumed with a high-fat meal, orange juice prevented the increase in LPS, oxidative stress, and inflammation compared to water or sugar water in a clinical trial on 30 people [68].

8) Peanuts
In a trial of 65 overweight men, consumption of a high-fat meal including peanuts lowered LPS levels compared to the same high-fat meal without peanuts. Consuming peanuts high in oleic acid had the strongest effect [69].

9) Bilberries
Consumption of 400 g/day of bilberries for 8 weeks reduced LPS, CRP, IL-6, and IL-12 in a small trial of 27 participants [70].

10) Exercise
Sedentary people have higher blood LPS levels than highly-trained people [71].

13) Lactoferrin（乳鐵蛋白）
Lactoferrin is a protein found in milk, tears, and saliva that is part of the immune system and protects against bacteria and fungi.

Potential healthy ways to reduce LPS include cooking with olive oil and eating foods high in pre- and probiotics, polyphenols, and omega-3 fatty acids. Meditation and vagus nerve stimulation might also help, according to limited research data.（橄欖油烹飪，吃富含益生菌、多酚和ω-3脂肪酸的食物）

上面內容來自【4】

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下面內容來自【6】

LPS content both in cecal contents and blood was concomitantly increased by fat ingestion [9], and this increase of LPS was suppressed with oral administration of intestinal alkaline phosphatase, a LPS inactivating enzyme [9]. Oral administration of ampicillin and neomycin, broad-spectrum antibiotics that are poorly absorbed, also suppressed the increase in blood LPS concentration induced by a high-fat diet [10].These reports suggest that intestinal bacteria are an important source of LPS. In particular, Cani et al. demonstrated changes in intestinal flora (reduction in Bacteroides, Bifidobacterium, and Eubacterium) due to a high-fat diet. （脂肪攝入導致盲腸內容物和血液中LPS含量同時增加[9]，口服LPS失活酶腸道堿性磷酸酶可抑制LPS含量的增加[9]。口服氨芐西林和新霉素（吸收不良的廣譜抗生素）也能抑制高脂飲食引起的血LPS濃度升高[10]。這些報告表明，腸道細菌是LPS的重要來源。特別是，Cani等人證明了由于高脂肪飲食引起的腸道菌群變化（類桿菌、雙歧桿菌和真桿菌減少）。因此，高脂飲食引起的腸道菌群失調作為代謝性內毒素血癥的可能原因引起了人們的關注）

Changes in the intestinal bacteria due to ingestion of a high-fat diet have been studied in animals and humans and have been summarized in a review by Netto Candido et al. [11]（已經在動物和人類中研究了因攝入高脂肪飲食引起的腸道細菌變化，并在Netto Candido等人的綜述中進行了總結[11]）

?In animals, it has been reported that a high-fat diet increases the proportion of Firmicutes, Proteobacteria, and the ratio of Firmicutes to Bacteroidetes（另一方面，據報道，在人類中，高脂肪飲食攝入會增加類桿菌的比例，降低厚壁菌和變形菌的比例）

Devkota et al. evaluated the gut microbiota in C57BL/6 mice fed a low-fat diet, a high-fat diet with lard, or a high-fat diet with milk fat for 21 days [12]. In this experiment, both high-fat diets were isocaloric, rich in saturated fatty acids, and 37% of the ingested kcal were from fat. As a result, the proportion of Firmicutes increased and that of Bacteroidetes decreased in the gut microbiota of mice fed a high-fat diet containing lard, compared to mice fed a low-fat diet. In contrast, in mice fed a high-fat diet containing milk fat, the proportion of Firmicutes decreased and that of Bacteroidetes increased compared to the low-fat diet fed mice. Interestingly, Devkota et al. also identified specific bacteria that increased only by ingestion of a high-fat diet containing milk fat [12]. Compared to mice fed a low-fat diet, or a high-fat diet containing lard, mice fed with a high-fat diet containing milk fat had increased proportions of Bilophila wadsworthia, a sulfite-reducing bacterium, in gut microbiota. They also elucidated the mechanism underlying this increase; intake of milk fat increased the level of taurocholic acid in bile. Bilophila wadsworthia populations increased by utilizing sulfur components in taurocholic acid, causing intestinal inflammation in mice. An increase in total fecal bile acid and a concomitant increase in Bilophila wadsworthia in the gut microbiota was also reported in humans upon dietary intake of animal fat [13]. Natividad et al. also showed that increased Bilophila wadsworthia in mice fed a high-fat diet contributed to increased blood LPS levels (they measured soluble CD14 as a surrogate marker), increased fasting blood glucose levels, and the development of a fatty liver [14].?

（Devkota等人評估了喂食低脂飲食、含豬油的高脂飲食或含乳脂的高脂飲食21天的C57BL/6小鼠的腸道微生物群[12]。在這個實驗中，兩種高脂肪飲食都是等熱量的，富含飽和脂肪酸，37%的攝入的KCl來自脂肪。因此，與喂食低脂飲食的小鼠相比，喂食含豬油的高脂飲食的小鼠腸道微生物群中厚壁菌的比例增加，擬桿菌的比例減少。相反，與低脂飲食喂養的小鼠相比，在喂食含乳脂的高脂飲食的小鼠中，厚壁菌的比例減少，擬桿菌的比例增加。有趣的是，Devkota等人還發現了僅通過攝入含有乳脂的高脂肪飲食而增加的特定細菌[12]。與喂食低脂飲食或含豬油的高脂飲食的小鼠相比，喂食含乳脂的高脂飲食的小鼠腸道微生物群中嗜亞硫酸鹽還原菌Bilophila wadsworthia的比例增加。他們還闡明了這種增長的機制；攝入乳脂會增加膽汁中牛磺膽酸的水平。通過利用牛磺膽酸中的硫成分，使Bilophila wadsworthia種群增加，導致小鼠腸道炎癥。在人類飲食中攝入動物脂肪后，還報告了糞便總膽汁酸的增加以及腸道微生物群中嗜膽汁菌的伴隨增加[13]。Natividad等人還表明，喂食高脂飲食的小鼠體內嗜Bilophila wadsworthia的增加有助于血液LPS水平的增加（他們測量可溶性CD14作為替代標記物）、空腹血糖水平的增加以及脂肪肝的發展[14]。）

It is also necessary to consider dietary LPS as a source of LPS. For example, milk has been reported to contain high concentrations of LPS in some commercial products [15]. Multiple animal studies have reported that ingested LPS may contribute to increased blood LPS levels. Specifically, Kaliannan et al. measured blood LPS levels 45 min after ingestion of LPS alone or corn oil and LPS in mice [9]. It showed that blood LPS levels were elevated when corn oil and LPS were co-administered. Lindenberg et al. reported that LPS concentrations in the blood were higher in mice fed a high-fat diet containing LPS than in mice fed a high-fat diet without LPS [16]. However, the effect of LPS levels in food on blood LPS levels has not been adequately studied in humans and further studies are needed.

（還需要考慮膳食LPS作為LPS的來源。例如，據報道，牛奶在一些商業產品中含有高濃度的LPS[15]。多項動物研究報告，攝入LPS可能導致血液LPS水平升高。特別是，Kaliannan等人在小鼠單獨攝入LPS或玉米油和LPS 45分鐘后測量了血LPS水平[9]。結果表明，當玉米油和LPS合用時，血液LPS水平升高。Lindenberg等人報告，喂食含LPS的高脂飲食的小鼠血液中的LPS濃度高于喂食不含LPS的高脂飲食的小鼠[16]。然而，食物中LPS水平對人類血液LPS水平的影響尚未得到充分研究，需要進一步研究）

The limulus amebocyte lysate assay used to measure LPS recognizes lipid A, a glycolipid moiety of LPS [17], but because lipid A is embedded in the outer membrane of gram-negative bacteria [18], elevated blood LPS levels suggest that LPS released from gram-negative bacteria is flowing into the blood. In an in vitro study with Escherichia coli, the concentration of free LPS in the culture medium increased with bacterial growth, but the addition of antibiotics stimulated further LPS release [19]. In addition, Jin et al. suggested that treatment with penicillin and erythromycin killed the gram-negative bacteria, Bacteroides and γ-Proteobacteria, leading to increased blood LPS levels in mice [20].?

（青霉素、紅霉素殺死革蘭氏陰性菌會導致該細菌釋放LPS進入血液，血液LPS水平升高）

Although the ratio of fat to energy intake varied, it has been reported that blood LPS levels increased by consumption of a high-fat diet with 30% of kcal ingested being from fat [32,33].Therefore, the reason for the lack of increase in blood LPS levels in the study of Reichardt et al. is not considered to be a difference in the fat content of the diet（高脂肪攝入會導致LPS升高）

It is reported that blood LPS is bound to various lipoproteins, with plasma LPS concentrations of 31%, 30%, 29%, and 10% for the very low-density lipoprotein (VLDL) fraction, low-density lipoprotein (LDL) fraction, high-density lipoprotein (HDL) fraction, and free LPS, respectively [36].

與血漿LPS結合的各類物質	比例
超低密度脂蛋白（VLDL）	31%
低密度脂蛋白（:LDL）	30%
高密度脂蛋白（HDL）	29%
游離LPS	10%

Increased LPS content has been reported in the livers of mice fed a high-fat diet [43], suggesting that the liver is an important site for LPS clearance. Ninety percent of the free LPS that entered the bloodstream is captured by liver resident macrophages (i.e., Kupffer cells) within 1 h [44]. LPS bound to HDL attaches primarily to sinusoidal epithelial cells of the liver [40,44], but it shows slower blood kinetics than free LPS, with 50% present in plasma even 1 h after administration and the amount accumulated in the liver accounted for only 15% of the dose [44]. LPS bound to HDL on the other hand is distributed widely to organs other than the liver, such as the kidney and adipose tissue [44]. LPS accumulated in the liver is inactivated by acyloxyacyl hydroxylase produced by Kupffer cells regardless of free or HDL-bound form [44]. Previously, in a mouse model of high-fat diet plus streptozotocin-induced non-alcoholic steatohepatitis-hepatocellular carcinoma, fecal LPS levels were continuously elevated from six weeks, while liver LPS levels were transiently elevated at eight weeks, followed by increased plasma LPS levels [45]. This report suggests that the liver acts as the first barrier against LPS entering from the intestinal tract and that liver dysfunction leads to elevated blood LPS levels. Interestingly, LPS administration in mice increased the expression of apolipoprotein AIV in the liver via TLR4, suggesting that the liver has a mechanism to increase HDL production and protect itself against LPS stimulation [46].（據報道，喂食高脂飲食的小鼠肝臟中LPS含量增加[43]，表明肝臟是清除LPS的重要部位。進入血流的90%游離LPS在1小時內被駐留在肝臟的巨噬細胞（即枯否細胞）捕獲[44]。與高密度脂蛋白結合的LPS主要附著于肝竇上皮細胞[40,44]，但其血液動力學比游離LPS慢，即使給藥后1小時，血漿中仍有50%的LPS存在，肝臟中的累積量僅占劑量的15%[44]。另一方面，與HDL結合的LPS廣泛分布于肝臟以外的器官，如腎臟和脂肪組織[44]。累積在肝臟中的LPS被Kupffer細胞產生的酰氧基羥化酶滅活，無論游離形式或HDL結合形式如何[44]。此前，在高脂飲食加鏈脲佐菌素誘導的非酒精性脂肪性肝炎肝細胞癌的小鼠模型中，糞便LPS水平從6周開始持續升高，而肝臟LPS水平在8周時短暫升高，隨后血漿LPS水平升高[45]。該報告表明，肝臟是阻止LPS從腸道進入的第一道屏障，肝功能障礙導致血LPS水平升高。有趣的是，給小鼠注射LPS可通過TLR4增加肝臟中載脂蛋白AIV的表達，這表明肝臟具有增加HDL生成和保護自身免受LPS刺激的機制[46]）

Since metabolic endotoxemia has been implicated in gut dysbiosis, the effects of probiotics have been investigated. However, the results in humans are unfavorable (Table 1).（有張表格是吃哪些東西能讓LPS下降）

?In addition, Pei et al. studied whether low-fat yogurt could be administered before a meal to suppress the increase in blood LPS after a meal [50] and found no efficacy. On the other hand, there have been several reports of the efficacy of probiotics in animal studies (Table 3) [43,51,52,53,54,55]. Lactobacillus rhamnosus, Lactobacillus sakei, Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium longum, Bifidobacterium infantis, and Bacillus cereus are used as species, and the dosage ranges from 107 to 1010 CFU/day for four to twelve weeks. These animal studies used a high-fat diet, a high-fat high-sucrose diet, or a Zucker-Lepfa/fa obesity model. In addition to a significant decrease in blood LPS or LBP levels, improvement of obesity, glucose metabolism, and dyslipidemia was also observed. Since the effects of probiotics are strain-specific, it is expected that the effects of strains that have been effective in animal studies will be verified in humans.（此外，Pei等人研究了是否可以在飯前服用低脂酸奶來抑制飯后血LPS的增加[50]，但沒有發現任何效果。另一方面，在動物研究中已經有一些關于益生菌功效的報告（表3）[43,51,52,53,54,55]。鼠李糖乳桿菌、sakei乳桿菌、嗜酸乳桿菌、植物乳桿菌、長雙歧桿菌、嬰兒雙歧桿菌和蠟樣芽孢桿菌用作菌種，劑量范圍為107至1010 CFU/天，持續4至12周。這些動物研究采用高脂肪飲食、高脂肪高蔗糖飲食或Zucker-Lepfa/fa肥胖模型。除了顯著降低血LPS或LBP水平外，還觀察到肥胖、糖代謝和血脂異常的改善。由于益生菌的作用是菌株特異性的，預計在動物研究中有效的菌株的作用將在人類身上得到驗證。）

In intervention studies with oligofructose [57] and inulin [58,59], subjects with obesity, overweight subjects, and subjects with type 2 diabetes consumed 10–21 g of test substances for 8–12 weeks. Two of the three studies showed a significant decrease in blood LPS levels [57,58].（低聚果糖、菊糖）

?In mice, chronic administration of LPS has been reported to induce hyperphagia by decreasing leptin sensitivity of afferent vagal nerves [66], and the reduced blood LPS levels and appetite suppression seen with galacto-oligosaccharide administration are of interest in supporting an association between LPS and appetite.（低聚半乳糖 降低LPS）

3.3. Polyphenols
Polyphenols are secondary metabolites found in plants and are responsible for protection against oxidative stress, UV damage, and pathogenic microorganisms [67]. Polyphenols are found in a wide range of foods, including vegetables, fruits, tea, beans, and spices, and their consumption has been reported to improve metabolic syndrome (decreased body weight, decreased blood pressure, improved glucose metabolism, and improved lipid metabolism) [68]. However, up to 27% of ingested polyphenols are detected in urine [69], suggesting that many of them are not absorbed and reach the large intestine [70]. Since polyphenols reaching the large intestine have been reported to alter the proportions of microbiota [71], it is expected that the effect of polyphenols against metabolic syndrome is mediated through the improvement of dysbiosis and of the accompanying metabolic endotoxemia. There are two human intervention studies investigating the relationship between polyphenol intake and blood LPS, both of which evaluated the inhibitory effect on postprandial elevation of blood LPS levels (Table 1) [72,73]. In the study performed by Ghanim et al., healthy individuals ingested capsules containing 100 mg of resveratrol and 75 mg of polyphenol 10 min before a 930-kcal high-fat, high-carbohydrate meal. Blood LBP levels up to 5 h after a meal were evaluated and showed increased blood LBP levels in the placebo group but not in the capsule group [72]. On the other hand, Clemente-Postigo et al. administered 272 mL of red wine to humans simultaneously with excessive fat and found no effect on either blood LPS or LBP levels [73]. The efficacy of polyphenols has been also reported in animal studies. The effects of grape seed proanthocyanin [29,33], resveratrol [74], apple-derived polymeric procyanidins [75], genistein [76], isoflavone [77], and syringarecinol [78] on blood LPS levels in animal models have been reported (Table 3). In particular, L’openz et al. reported that six-month administration of genistein to high-fat diet-fed mice reduced their blood LPS levels and improved their spatial memory ability [76]. Cho et al. administered syringalesinol to 40-week-old mice for 10 weeks and showed that the decrease in blood LBP levels was accompanied with suppression of changes in immune cells due to aging (decreased naive T cells and decreased T-cell proliferation) [78]. It has also been reported that adoption of a high-fat diet results in abnormal differentiation of bone marrow hematopoietic stem cells due to increased blood LPS levels [79], suggesting that the effect of syringalecinol on immunoaging might be also exerted in other models of metabolic endotoxemia.

（3.3. 多酚類物質

多酚是植物中的次生代謝物，負責保護植物免受氧化應激、紫外線損傷和病原微生物[67]。多酚廣泛存在于各種食品中，包括蔬菜、水果、茶、豆類和香料，據報道，食用多酚可改善代謝綜合征（體重下降、血壓下降、糖代謝改善和脂質代謝改善）[68]。然而，在尿液中檢測到多達27%的攝入多酚[69]，這表明其中許多多酚沒有被吸收并到達大腸[70]。由于有報道稱到達大腸的多酚類物質會改變微生物群的比例[71]，因此，預計多酚類物質對代謝綜合征的作用是通過改善失調和伴隨的代謝性內毒素血癥來實現的。有兩項人類干預研究調查了多酚攝入與血LPS之間的關系，這兩項研究都評估了對餐后血LPS水平升高的抑制作用（表1）[72,73]。在Ghanim等人進行的研究中，健康人在930 kcal高脂肪、高碳水化合物膳食前10分鐘攝入含有100 mg白藜蘆醇和75 mg多酚的膠囊。對餐后5小時內的血LBP水平進行評估，發現安慰劑組的血LBP水平升高，而膠囊組的血LBP水平沒有升高[72]。另一方面，Clemente Postigo等人同時給人服用了272毫升紅葡萄酒和過量脂肪，并發現對血液LPS或LBP水平沒有影響[73]。多酚類物質的功效在動物研究中也有報道。已經報道了葡萄籽原花青素[29,33]、白藜蘆醇[74]、蘋果衍生的聚合原花青素[75]、染料木素[76]、異黃酮[77]和丁香沒食子酸[78]對動物模型血液LPS水平的影響（表3）。特別是，L'openz等人報告說，對高脂飲食喂養的小鼠給予染料木素6個月，可降低其血液LPS水平，并改善其空間記憶能力[76]。Cho等人給40周齡的小鼠服用丁香醛醇10周，結果表明，血液LBP水平的降低伴隨著衰老導致的免疫細胞變化的抑制（原始T細胞減少，T細胞增殖減少）[78]。也有報道稱，由于血液LPS水平升高，采用高脂飲食導致骨髓造血干細胞異常分化[79]，這表明丁香醇對免疫老化的影響也可能在其他代謝性內毒素血癥模型中發揮作用。）

3.4. Sulfated Polysaccharide
Sulfated polysaccharides are widely present in animal tissues and seaweed and are used industrially as anticoagulants, pharmaceuticals, and gelling agents for foods. The effect of sulfated polysaccharides on metabolic endotoxemia has been studied only in animals (Table 3). Intervention studies with sea cucumber-derived sulfated polysaccharides [80,81], acaudina molpadioides-derived fucosylated chondroitin sulfate [82], chicken-derived chondroitin sulfate [83] or fucoidan [84] have been performed. Of these studies, two showed that administration of sulfated polysaccharides to high-fat diet-fed mice increased the amount of short-chain fatty acids in the intestinal tract, decreased the blood LPS or LBP concentration and attenuated weight gain [80,82]. Zhu et al. also reported the same effect of sulfated polysaccharides in chow-fed lean mice [81]. Liu et al. demonstrated that exhaustive exercise with a treadmill significantly impaired kidney function, decreased fecal butyrate levels, changed intestinal morphology, and induced metabolic endotoxemia [83]. Their study is interesting in showing that exercise stress also increased blood LPS levels, and that dietary factors are also effective in the model mice.(3.4. 硫酸多糖

硫酸多糖廣泛存在于動物組織和海藻中，在工業上用作抗凝劑、藥物和食品膠凝劑。硫酸多糖對代謝性內毒素血癥的影響僅在動物中進行了研究（表3）。已經對海參衍生的硫酸多糖[80,81]、acaudina molpadioides衍生的巖藻糖基硫酸軟骨素[82]、雞肉衍生的硫酸軟骨素[83]或巖藻糖膠[84]進行了干預研究。其中兩項研究表明，向高脂飲食喂養的小鼠施用硫酸多糖可增加腸道內短鏈脂肪酸的數量，降低血液LPS或LBP濃度，并減少體重增加[80,82]。Zhu等人還報告了硫酸多糖對周飼瘦肉小鼠的相同作用[81]。Liu等人證明，在跑步機上進行力竭運動會顯著損害腎功能，降低糞便丁酸水平，改變腸道形態，并誘發代謝性內毒素血癥[83]。他們的研究有趣地表明，運動應激也會增加血LPS水平，飲食因素對模型小鼠也有效。)

3.5. Other Dietary Components/Extracts/Foods
In the study by Abboud et al., obese or over weight subjects ingested 30 g of glutamine per day for eight weeks (Table 1) [85]. As a result, their blood LPS levels and waist circumference decreased. In an epidemiological study conducted with healthy subjects, 25-hydroxy vitamin D was reported to negatively correlate to blood LPS levels (Table 2) [86]. The protective effect of vitamin D is supported by animal studies in which vitamin D-deficient mice, exposed to a bacterial pathogen, exhibited lower LPS detoxification activity of the intestine and greater endotoxin translocation [87]. The effect of other dietary components, including tetrahydro iso-alpha acid [88], rhein [89], phlorizin [90], capsaicin [91], rutin [92], and lycopene [93] on blood LPS levels in animals has also been reported (Table 3). Among them, administration of tetrahydro iso-alpha acid [88], phlorizin [90], or rutin [92] to high-fat diet-fed mice or db/db mice improved metabolic impairment. Administration of rhein [89], or lycopene [93] to high-fat diet-fed mice showed a unique effect; they not only reduced blood LPS levels but also prevented high-fat diet-induced memory impairment. Kang et al. showed that administration of antibiotics to mice given capsaicin abolished the effect of capsaicin on blood LPS levels [91]. They also showed that capsaicin-induced protection against high-fat diet-induced blood LPS increase is transferrable by fecal microbiota transplantation.
It has also been reported that intervention with crude food extracts or the food itself can lower blood LPS levels in animals (Table 3). We studied the effect of broccoli sprout extract, enriched in functional glucosinolate “glucoraphanin” (details are described in Section 4) [94]. Anhê et al. examined the effects of extracts from cranberry [95] or camu camu [96]. Camu camu is an Amazonian fruit that contains an abundance of vitamin C and flavonoids such as ellagic acid, ellagitannins, and proanthocyanidins. Administration of camu camu extracts to high-fat/high-sucrose diet-fed mice reduced plasma bile acid pool size, altered gut microbiota composition, and reduced blood LPS levels. Dey et al. reported that administration of green tea extract to high-fat diet-fed mice suppressed inflammation and gut permeability especially in the ileum and colon, and reduced LPS influx from the portal vein [34]. The reduction of blood LPS levels by feeding with Tartary buckwheat protein was reported by Zhou et al. [32]. This study is valuable in that it elucidates one of the underlying mechanisms by which plant protein intake leads to improvement of metabolic abnormalities. Intervention studies with cocoa [97], nopal [98], and steamed fish meat [99] have been performed. Among these, Zhang et al. performed unique experiments [99]. They divided mice into four groups, and fed them ad libitum with normal chow, steamed fish, pork or beef at 9:00 and 18:00 daily for eight weeks. As a result, only mice group fed with steamed fish showed decreased blood LBP levels compared to the other three groups.

（3.5. 其他膳食成分/提取物/食物

在Abboud等人的研究中，肥胖或超重受試者連續八周每天攝入30 g谷氨酰胺（表1）[85]。結果，他們的血LPS水平和腰圍下降。在對健康受試者進行的流行病學研究中，25-羥基維生素D與血液LPS水平呈負相關（表2）[86]。維生素D的保護作用得到了動物研究的支持，在動物研究中，維生素D缺乏的小鼠暴露于細菌病原體，表現出較低的腸道LPS解毒活性和較大的內毒素移位[87]。其他飲食成分，包括四氫異α酸[88]、大黃酸[89]、根皮苷[90]、辣椒素[91]、蘆丁[92]和番茄紅素[93]對動物血液LPS水平的影響也有報道（表3）。其中，向高脂飲食喂養的小鼠或db/db小鼠施用四氫異α酸[88]、根皮苷[90]或蘆丁[92]可改善代謝損傷。給高脂飲食喂養的小鼠服用大黃酸[89]或番茄紅素[93]顯示出獨特的效果；他們不僅降低了血液LPS水平，還防止了高脂肪飲食引起的記憶障礙。Kang等人證明，給給予辣椒素的小鼠服用抗生素可消除辣椒素對血液LPS水平的影響[91]。他們還表明，辣椒素誘導的對高脂飲食誘導的血LPS增加的保護作用可通過糞便微生物群移植進行轉移。

也有報道稱，用粗食物提取物或食物本身進行干預可以降低動物的血LPS水平（表3）。我們研究了西蘭花芽提取物的作用，該提取物富含功能性硫代葡萄糖苷“葡萄糖拉菲”（詳情見第4節）[94]。Anhê等人研究了蔓越莓[95]或卡姆卡姆[96]提取物的作用。Camu Camu是一種亞馬遜水果，含有豐富的維生素C和類黃酮，如鞣花酸、鞣花鞣花素和原花青素。向高脂/高糖飲食喂養的小鼠施用camu-camu提取物可減少血漿膽汁酸池大小，改變腸道微生物群組成，并降低血LPS水平。Dey等人報告稱，向高脂飲食喂養的小鼠施用綠茶提取物可抑制炎癥和腸道通透性，尤其是回腸和結腸，并減少門靜脈LPS流入[34]。Zhou等人[32]報告了通過喂食苦蕎蛋白降低血液LPS水平的情況。這項研究很有價值，因為它闡明了植物蛋白質攝入導致代謝異常改善的潛在機制之一。對可可[97]、nopal[98]和蒸魚肉[99]進行了干預研究。其中，Zhang等人進行了獨特的實驗[99]。他們將老鼠分為四組，每天9:00和18:00隨意喂食正常食物、蒸魚、豬肉或牛肉，持續八周。因此，與其他三組相比，只有喂食清蒸魚的小鼠組血液LBP水平降低。）

3.6. Chinese Medicines
The effect of the Chinese medicines; geniposide + chlorogenic acid [100], potentilla discolor bunge water extract [101], ganoderma lucidum mycelium water extract [102], semen hoveniae extract [103], and shenling baizhu powder [104] on blood LPS levels have been reported in animals (Table 3). The combination of geniposide and chlorogenic acid is included in a traditional Chinese medicine, Qushi Huayu Decoction. Peng et al. indicated that administration of geniposide and chlorogenic acid to high-fat diet-fed mice restored colonic tight junctions by inhibiting down-regulation of RhoA/Rho-associated kinase signaling, and reduced blood LPS levels and hepatic LBP protein levels [100]. Han et al. examined the effect of potentilla discolor bunge water extract in type 2 diabetic mice induced by high-fat diet feeding and streptozotocin injection [101]. The results showed that fecal LPS levels in the type 2 diabetic model mice were significantly increased compared to the control normal mice. The administration of potentilla discolor bunge water extract to mice reduced fecal LPS levels, decreased blood LPS levels and increased the expression levels of tight junction proteins (Claudin-3, ZO-1, and Occludin) in the colon. Chang et al. studied the effect of ganoderma lucidum mycelium, a Basidiomycete fungus [102]. They showed the dose-dependent effect of ganoderma lucidum mycelium water extract on blood LPS reduction, suggesting that high molecular weight polysaccharides (>300 kDa) isolated from the extract is an effective component. Ping et al. reported that the extract of semen hoveniae, a seed of Hovenia dulcis Thunb rich in dihydromyricetin and quercetin, decreased blood LPS levels in a mouse model of alcohol-induced liver injury [103]. It has been reported that administration of shenling baizhu, a mixture of ten different traditional Chinese medicinal herbs, to high-fat diet-fed mice decreased LPS levels in the portal vein [104].（3.6. 中藥

中藥的作用；已報告geniposide+綠原酸[100]、翻白草水提取物[101]、靈芝菌絲體水提取物[102]、枳實提取物[103]和神靈白術粉[104]對動物血液LPS水平的影響（表3）。梔子苷和綠原酸的組合包含在傳統中藥祛濕化瘀湯中。Peng等人指出，通過抑制RhoA/Rho相關激酶信號的下調，并降低血液LPS水平和肝臟LBP蛋白水平，向高脂飲食喂養的小鼠施用京尼平苷和綠原酸可恢復結腸緊密連接[100]。Han等人研究了翻白草水提取物對高脂飲食喂養和鏈脲佐菌素注射液誘導的2型糖尿病小鼠的影響[101]。結果表明，與對照正常小鼠相比，2型糖尿病模型小鼠的糞便LPS水平顯著升高。向小鼠施用翻白草水提取物可降低糞便LPS水平，降低血液LPS水平，并增加結腸中緊密連接蛋白（Claudin-3、ZO-1和Occludin）的表達水平。Chang等人研究了擔子菌靈芝菌絲體的作用[102]。他們顯示了靈芝菌絲體水提取物對降低血LPS的劑量依賴效應，表明從提取物中分離的高分子量多糖（>300kDa）是一種有效成分。Ping等人報道，在酒精誘導的肝損傷小鼠模型中，富含二氫楊梅素和槲皮素的枳實種子枳實提取物降低了血液LPS水平[103]。據報道，將十種不同中草藥的混合物神靈白術用于高脂飲食喂養的小鼠，可降低門靜脈的LPS水平[104]。）

3.7. Dietary Habits
In relation to dietary habits, Kopf et al. conducted an intervention study in humans with BMI > 25 kg/m2 and low intake of whole grains, fruits, and vegetables (Table 1) [65]. During the weekly interview, the subjects themselves selected the vegetables and fruits to be eaten the following week from apples, bananas, blueberries, clementines, grapes, pears, strawberries, broccoli, carrots, cauliflower, celery, green beans, green leaf lettuce, peas, spinach, sweet pepper, and tomatoes. The subjects ate these fruits and vegetables for 21 to 30 servings/week (at least three servings/day) for six weeks. As a result, compared to control group in that dietary habits were not or minimal changed, average daily intake of refined grains was 1/3, fruit intake was doubled, and vegetable intake was four times, leading to a significant reduction in blood LBP levels and IL-6 levels. An epidemiological study by Ahola et al. in patients with type 1 diabetes has shown a negative correlation between several dietary patterns and blood LPS levels: These dietary patterns are “Fish” (frequently eats fish dishes), “Healthy snack” (frequently eats fruits, berries, fresh vegetables, yoghurt, low-fat cheese, and does not drink many soft drinks) and “Modern” (frequently eats poultry, pasta, rice, meat dishes, fried and grilled foods, and fresh vegetables) (Table 2) [105]. In the epidemiological study by Ahola et al., no significant correlation was found between blood LPS levels and intake of energy, carbohydrates, fats, proteins, or dietary fiber. In regard to the absence of a significant positive correlation between blood LPS levels and fat intake (the believed cause of blood LPS elevation in humans and animals), the authors consider that the previously reported amount or proportion of fat intake may be greater than the intake in the normal diet. Similarly, Amar et al. reported no significant correlation between fat intake and blood LPS levels in 201 subjects [106]. In the same study, Amar et al. reported a positive correlation between total energy intake and blood LPS levels [106]. The effect of caloric restriction on blood LPS levels have been reported in both humans and mice. Ott et al. reported that, in women with a BMI of 30 kg/m2 or more, intake of a defined formula diet of 800 kcal/day for four weeks decreased blood LBP levels, and following intake of the normal diet (1800 kcal/day), blood LBP levels returned to the initial levels (Table 1) [107]. Even in mice, caloric restriction of 30% [108] or 40% [109] has been reported to decrease blood LPS or LBP levels (Table 3). A common finding in these reports in mice is that blood LPS or LBP levels are reduced by calorie restriction compared to ad libitum even in normal chow-fed mice. This suggests that the influx of LPS into the bloodstream is not limited to the specific conditions of excessive fat intake but can also occur by some mechanism in the normal diet.（3.7. 飲食習慣

關于飲食習慣，Kopf等人對體重指數>25 kg/m2且全谷物、水果和蔬菜攝入量較低的人進行了干預研究（表1）[65]。在每周訪談中，受試者自己從蘋果、香蕉、藍莓、克萊門汀、葡萄、梨、草莓、花椰菜、胡蘿卜、花椰菜、芹菜、青豆、綠葉萵苣、豌豆、菠菜、甜椒和西紅柿中選擇下周要吃的蔬菜和水果。受試者每周食用這些水果和蔬菜21至30份（每天至少3份），持續6周。因此，與對照組相比，飲食習慣沒有改變或變化很小，精制谷物的平均每日攝入量為1/3，水果攝入量增加了一倍，蔬菜攝入量增加了四倍，從而顯著降低了血液LBP水平和IL-6水平。Ahola等人對1型糖尿病患者進行的一項流行病學研究表明，幾種飲食模式與血LPS水平呈負相關：這些飲食模式是“魚”（經常吃魚菜），“健康零食”（經常吃水果、漿果、新鮮蔬菜、酸奶、低脂奶酪，不喝很多軟飲料）和“現代”（經常吃家禽、面食、米飯、肉類菜肴、油炸和燒烤食品以及新鮮蔬菜）（表2）[105]在Ahola等人的流行病學研究中，未發現血LPS水平與能量、碳水化合物、脂肪、蛋白質或膳食纖維攝入之間存在顯著相關性。關于血LPS水平與脂肪攝入之間缺乏顯著正相關性（據信是人和動物血LPS升高的原因）作者認為，先前報道的脂肪攝入量的數量或比例可能大于正常飲食中的攝入量。同樣，阿馬爾等人報告201名受試者的脂肪攝入量與血液LPS水平沒有顯著相關性（106）。在同一研究中，Amar等人報告了總能量攝入與血液LPS水平之間的正相關[106]。已報告熱量限制對人類和小鼠血液LPS水平的影響。Ott等人報告，在BMI為30 kg/m2或以上的女性中，連續四周攝入800 kcal/天的規定配方飲食可降低血液LBP水平，并且在攝入正常飲食（1800 kcal/天）后，血液LBP水平恢復到初始水平（表1）[107]。即使在小鼠中，據報道限制30%[108]或40%[109]的熱量也會降低血液LPS或LBP水平（表3）。在這些研究報告中，小鼠的一個常見發現是，即使在正常的周糧喂養的小鼠中，與隨意進食相比，熱量限制也會降低血LPS或LBP水平。這表明，LPS流入血流不僅限于脂肪攝入過多的特定情況，而且在正常飲食中也可能通過某種機制發生

）

4. Association of Dietary Factor-Induced Reduction of Blood LPS and Modulation of Gut Microbiota
Although few studies have evaluated the relationship between the effect of dietary factors on blood LPS and intestinal flora in humans, several studies have evaluated intestinal flora in oligosaccharide intervention studies (Table 1). A common finding in these reports is an increase in Bifidobacterium. Bifidobacterium has been reported to enhance the intestinal tight junction by preserving claudin 4 and occludin localization at tight junctions, and inhibit permeability in mice with colitis [115]. Similarly, in human colonic epithelial cell line T84, the addition of culture supernatant of Bifidobacterium has been reported to enhance barrier function through increased expression of tight junction protein, suggesting that some humoral factors contribute to improved intestinal barrier function [116]. Increased expression of tight junction protein in Bifidobacterium-treated mice has been reported to be associated with increased short-chain fatty acids (acetic acid, butyric acid, and propionic acid) in the intestinal tract [117]. These short-chain fatty acids have been reported in the human colonic epithelial cell line caco-2 to act as an energy source for epithelial cells to protect themselves, and also act as a histone deacetylase inhibitor which inhibit Nod-like receptor P3 inflammasomes to maintain the barrier function of epithelial cells [118]. These results suggest that the increase in Bifidobacterium induced by oligosaccharide intake decreases blood LPS levels through the improvement of the barrier function of the intestinal tract. In addition, dietary factors that increase Bifidobacterium are expected to reduce blood LPS levels.（4.飲食因素誘導的血LPS降低與腸道微生物群調節的關系

雖然很少有研究評估了飲食因素對人體血液LPS和腸道菌群的影響之間的關系，但有幾項研究在低聚糖干預研究中評估了腸道菌群（表1）。這些報告中的一個常見發現是雙歧桿菌增多。據報道，雙歧桿菌通過保留緊密連接處的claudin 4和occludin定位來增強腸道緊密連接，并抑制結腸炎小鼠的通透性[115]。類似地，在人類結腸上皮細胞系T84中，已報道添加雙歧桿菌培養上清液通過增加緊密連接蛋白的表達來增強屏障功能，這表明一些體液因素有助于改善腸屏障功能[116]。據報道，雙歧桿菌治療的小鼠緊密連接蛋白的表達增加與腸道內短鏈脂肪酸（乙酸、丁酸和丙酸）的增加有關[117]。據報道，這些短鏈脂肪酸存在于人類結腸上皮細胞系caco-2中，可作為上皮細胞保護自身的能量來源，也可作為組蛋白去乙酰化酶抑制劑，抑制Nod樣受體P3炎性體以維持上皮細胞的屏障功能[118]。這些結果表明，通過改善腸道屏障功能，低聚糖攝入誘導的雙歧桿菌增加降低了血LPS水平。此外，增加雙歧桿菌的飲食因素有望降低血液LPS水平。

）

Lactobacillus, Bacteroides, Akkermansia, Roseburia, and Prevotella are possible bacterial genera that may contribute to the reduction of blood LPS levels. Lactobacillus is a gram-positive bacterium that produces large amounts of lactic acid during carbohydrate fermentation. The probiotic contribution of Lactobacillus to the regulation of metabolic endotoxemia is studied (Table 3). Administration of Lactobacillus rhamnosus CNCM I-4036 to obese Zucker-Leprfa/fa rats decreased the mRNA expression levels of endothelin receptor type B (Ednrb) in the intestinal mucosa, and reduced the blood LBP level [52]. Reduction of Ednrb decreases the density of negative charge of the colonic mucin layer, leading to an increase in the ability of the mucin layer to adsorb microparticles and bacteria, thereby inhibiting their penetration through the colonic mucosa [119]. Lactobacillus sakei OK67 and PK16 are reported to suppress high-fat diet-induced colitis, and to reduce the fecal Proteobacteria population and fecal LPS levels in mice [53]. In addition to the previous reports described in Table 3, it has been reported that oral administration of Lactobacillus reuteri ZJ617 suppresses LPS-induced apoptosis of intestinal epithelial cells and maintains the intestinal barrier function [120]. We have described in Section 2.2 that LPS is absorbed from the intestinal tract during lipid absorption. Interestingly, oral ingestion of Lactobacillus acidophilus ATCC 4356 in mice has been reported to reduce the mRNA levels of Niemann-Pick C1-like 1, which is involved in lipid absorption in the intestine, and in the suppression of cholesterol absorption [121]. Taken together, this suggests that Lactobacillus contributes to a decrease in blood LPS levels through strengthening the intestinal barrier, reducing the amount of LPS in feces, and suppressing lipid absorption. As described in Table 4, Bifidobacterium, oligofructose, galacto-oligosaccharide, syringaresinol, acaudina molpadioides-derived fucosylated chondroitin sulfate, green tea extract, Tartary buckwheat protein, nopal, semen hoveniae extract, and 30% caloric restriction are dietary factors that increase the proportion of Lactobacillus in the gut microbiota. Among them, the amylolytic Bifidobacterium strain is reported to stimulate the growth of a nonamylolytic Lactobacillus probably by producing intermediate metabolites of starch metabolism [122]. Oligosaccharides (oligofructose and galacto-oligosaccharide) were reported to support the growth of Lactobacillus as prebiotics [123]. Green tea extract [124] and buckwheat-resistant starch [125] were reported to promote the growth of Lactobacillus in a fermentation assay. On the other hand, in an in vitro fermentation assay using gut microbiota, it was reported that fucosylated chondroitin sulfate promotes the growth of Bacteroides, Bifidobacterium, and Clostridium, while the number of Lactobacillus decreases [126]. Thus, the mechanism by which Lactobacillus increased in mice fed with fucosylated chondroitin sulfate needs to be further studied. The mechanism by which the proportion of Lactobacillus in gut microbiota increases due to calorie restriction also remains unknown. As it has been reported that the bacteria adapted to the nutritional environment can grow predominantly in the gut microbiota consortium [127], Lactobacillus might be able to grow even under malnutrition. The effect of syringaresinol, nolpal, and semen hoveniae on the growth of Lactobacillus has not been revealed.
Bacteroides is a gram-negative obligate anaerobe. Hooper et al. reported that Bacteroides thetaiotaomicron, a prominent component of the normal mouse and human intestinal microflora, modulates expression of genes involved in mucosal barrier fortification [128]. The administration of Bacteroides fragilis HCK-B3 and Bacteroides ovatus ELH-B2 to mice attenuated LPS-induced intestinal inflammation, by either modulating cytokine production or restoring the Treg/Th-17 balance [129]. On the other hand, in a state in which no dietary fiber is ingested, it has been suggested that Bacteroides degrades the mucin layer of the intestinal tract, decreases the barrier function of mucus, and induces inflammation [130]. Therefore, it should be noted that depending on the diet of the host, Bacteroides can act as either probiotics or pathobionts. As described in Table 4, an increase in Bacteroides was reported in four out of five intervention studies with sulfated polysaccharides. Bacteroides is a unique bacterium among gut flora that has degrading enzymes corresponding to various sulfated polysaccharides [131] and is able to utilize sulfated polysaccharides such as heparin [131], heparan sulfate [131], and chondroitin sulfate [132] as energy sources. It is therefore thought that intake of sulfate polysaccharide preferentially nourishes Bacteroides in gut flora and suppresses metabolic endotoxemia via its anti-inflammatory and barrier function-enhancing effects.

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乳酸桿菌、類桿菌、阿克曼菌、玫瑰桿菌和普氏桿菌可能是有助于降低血液LPS水平的細菌屬。乳酸桿菌是一種革蘭氏陽性細菌，在碳水化合物發酵過程中產生大量乳酸。研究了乳酸桿菌對調節代謝性內毒素血癥的益生菌作用（表3）。向肥胖Zucker-Leprfa/fa大鼠施用鼠李糖乳桿菌CNCM I-4036可降低腸粘膜中內皮素B型受體（Ednrb）的mRNA表達水平，并降低血LBP水平[52]。Ednrb的減少降低了結腸粘蛋白層的負電荷密度，導致粘蛋白層吸附微粒和細菌的能力增加，從而抑制其穿透結腸粘膜[119]。據報道，sakei OK67乳酸桿菌和PK16可抑制高脂飲食誘導的結腸炎，并可減少小鼠糞便中的變形菌群和糞便LPS水平[53]。除表3中所述的先前報告外，據報道，口服reuteri乳酸桿菌ZJ617可抑制LPS誘導的腸上皮細胞凋亡，并維持腸屏障功能[120]。我們在第2.2節中描述了脂多糖在脂質吸收過程中從腸道吸收。有趣的是，據報道，小鼠口服嗜酸乳桿菌ATCC 4356可降低參與腸道脂質吸收和抑制膽固醇吸收的Niemann-Pick C1樣1的mRNA水平[121]。綜上所述，這表明乳酸桿菌通過加強腸道屏障、減少糞便中LPS的數量和抑制脂質吸收，有助于降低血LPS水平。如表4所述，雙歧桿菌、低聚果糖、低聚半乳糖、丁香樹脂醇、acaudina molpadioides衍生巖藻糖基化硫酸軟骨素、綠茶提取物、苦蕎蛋白、nopal、枳實提取物、，30%的熱量限制是增加腸道微生物群中乳酸桿菌比例的飲食因素。其中，據報道，淀粉分解雙歧桿菌菌株可能通過產生淀粉代謝的中間代謝物來刺激非淀粉分解乳酸桿菌的生長[122]。據報道，低聚糖（低聚果糖和低聚半乳糖）作為益生元支持乳酸桿菌的生長[123]。據報道，綠茶提取物[124]和蕎麥抗性淀粉[125]在發酵試驗中可促進乳酸桿菌的生長。另一方面，在使用腸道微生物群進行的體外發酵試驗中，據報道巖藻糖基硫酸軟骨素促進類桿菌、雙歧桿菌和梭菌的生長，而乳酸桿菌的數量減少[126]。因此，食用巖藻糖基化硫酸軟骨素的小鼠中乳酸桿菌增加的機制需要進一步研究。由于熱量限制，腸道微生物群中乳酸桿菌比例增加的機制也尚不清楚。據報道，適應營養環境的細菌主要在腸道微生物群中生長[127]，即使在營養不良的情況下，乳酸桿菌也可能生長。丁香樹脂醇、諾爾帕爾和枳實對乳酸桿菌生長的影響尚未揭示。

類桿菌是一種革蘭氏陰性專性厭氧菌。Hooper等人報道，類桿菌thetaiotaomicron是正常小鼠和人類腸道微生物區系的重要組成部分，可調節參與粘膜屏障強化的基因表達[128]。向小鼠施用脆弱類桿菌HCK-B3和卵形類桿菌ELH-B2可通過調節細胞因子的產生或恢復Treg/Th-17平衡來減輕LPS誘導的腸道炎癥[129]。另一方面，在不攝入膳食纖維的狀態下，有人認為類桿菌會降解腸道的粘蛋白層，降低粘液的屏障功能，并誘發炎癥[130]。因此，應注意，根據宿主的飲食，類桿菌可作為益生菌或致病菌。如表4所述，五分之四的硫酸多糖干預研究報告類桿菌增加。類桿菌是腸道菌群中的一種獨特細菌，具有與各種硫酸多糖相對應的降解酶[131]，能夠利用硫酸多糖，如肝素[131]、硫酸乙酰肝素[131]和硫酸軟骨素[132]作為能源。因此，人們認為攝入硫酸多糖優先營養腸道菌群中的類桿菌，并通過其抗炎和屏障功能增強作用抑制代謝性內毒素血癥。）

Akkermansia is a mucin-adherent intestinal bacterium [133], which grows by degrading mucin [134], and produces propionic acid, a short-chain fatty acid [135]. In addition, Akkermansia promotes butyrate production, by supporting the growth of Anaerostipes caccae through mucin degradation [136]. As noted above, these short-chain fatty acids are known to enhance intestinal barrier function. In addition, it has been reported that Akkermansia-derived extracellular vesicles administered in mice are localized to the large intestine, and directly enhance intestinal barrier function by increasing epithelial cell expression of tight junction proteins [137]. Furthermore, oral administration of Akkermansia to mice inhibited high-fat diet-induced thinning of the mucin layer, reduced blood LPS concentration, and inhibited obesity and abnormal glucose metabolism [138]. Akkermansia has been reported to be negatively correlated with obesity (waist-to-hip ratio and subcutaneous adipocyte diameter) and diabetes mellitus (glucose intolerance states), and is attracting attention as a next-generation probiotic [139]. Among the dietary factors that increase the proportion of Akkermansia in the gut flora, polyphenols are intriguing because most of intervention studies with polyphenols (apple-derived polymeric procyanidins, genistein, and isoflavone) or polyphenol-rich food extracts (camu camu extract, cranberry extract, and green tea extract) consistently reported an increase of Akkermansia (Table 4). Anhê et al. reported that cranberry extract administration to mice increased colonic Kruppel-like factor 4 (a marker of goblet cells) and Muc2 mRNA expression, suggesting that polyphenols enhance mucin production and support the growth of Akkermansia [95]. On the other hand, direct prebiotic action of polyphenols to Akkermansia has been reported in a study using the Simulator of Human Intestinal Microbial Ecosystem (SHIME?) [140].
Roseburia [141] is an enteric bacterium that utilizes dietary fiber and may enhance intestinal barriers by producing butyric acid. It has been reported that administration of Roseburia to mice enhanced differentiation of regulatory T cells in the intestinal lamina propria and suppressed intestinal inflammation [142]. As described in Table 4, oligofructose, apple-derived polymeric procyanidins, sea cucumber-derived sulfated polysaccharide, camu camu extract, and ganoderma lucidum mycelium water extract were reported to increase the proportion of Roseburia in the gut flora. Roseburia metabolizes oligofructose into fructose, which is used for growth, but for this process, acetic acid that is produced by Bifidobacterium is required [143]. Therefore, in order to grow Roseburia by oligofructose intake, it is necessary to pay attention to the symbiotic relationship with other intestinal bacteria and the amount of short-chain fatty acids in the intestine. Other dietary factors, procyanidins, sea cucumber-derived sulfated polysaccharide, camu camu extract, and ganoderma lucidum mycelium, have not been studied for their prebiotic function for Roseburia.
It has been suggested that LPS from Prevotella has fewer phosphate and acyl moieties contributing to endotoxin activity, resulting in a lower TLR4 stimulatory capacity than LPS from Salmonella [144]. Therefore, by increasing the population of Prevotella in the intestinal flora, endotoxin activity in the intestinal contents and damage to intestinal epithelial cells might be decreased, leading to the reduction of blood LPS levels. On the other hand, Prevotella produces succinate as a metabolite of sugar metabolism [145]. It has also been reported that succinate from intestinal bacteria is utilized by and promotes growth of Salmonella serovar Typhimurium [146] and Clostridium difficile [147], which are the pathogens of pseudomembranous colitis. Succinate has also been reported to induce colitis via succinate receptors and to promote colonic fibrosis [148]. In addition, proportion of Prevotella in the gut flora has been reported to be positively correlated with blood LPS levels in patients with type 2 diabetes [149]. Thus, an increase in the proportion of Prevotella does not necessarily have a positive effect on intestinal health. It is necessary to carefully investigate the contribution of Prevotella to blood LPS levels.（

Akkermansia是一種粘蛋白粘附的腸道細菌[133]，通過降解粘蛋白[134]生長，并產生丙酸，一種短鏈脂肪酸[135]。此外，Akkermansia通過粘蛋白降解支持仙人掌的生長，促進丁酸鹽的生產[136]。如上所述，已知這些短鏈脂肪酸可增強腸道屏障功能。此外，據報道，在小鼠體內施用的阿克曼氏菌衍生的細胞外小泡定位于大腸，并通過增加緊密連接蛋白的上皮細胞表達直接增強腸屏障功能[137]。此外，給小鼠口服阿克曼菌可抑制高脂飲食誘導的粘蛋白層變薄，降低血LPS濃度，并抑制肥胖和異常糖代謝[138]。據報道，Akkermansia與肥胖（腰臀比和皮下脂肪細胞直徑）和糖尿病（葡萄糖不耐受狀態）呈負相關，并作為下一代益生菌引起了人們的關注[139]。在增加腸道菌群中阿克曼病比例的飲食因素中，多酚是一個有趣的因素，因為大多數干預研究使用多酚（蘋果衍生的聚合原花青素、染料木素和異黃酮）或富含多酚的食品提取物（卡姆卡姆提取物、蔓越莓提取物和綠茶提取物）持續報告Akkermansia增加（表4）。Anhê等人報道，給小鼠服用蔓越莓提取物可增加結腸Kruppel樣因子4（杯狀細胞的標記物）和Muc2 mRNA的表達，表明多酚可促進粘蛋白的產生并支持阿克曼氏菌的生長[95]。另一方面，在一項使用人類腸道微生物生態系統模擬器（SHIME?）的研究中報告了多酚對阿克曼菌的直接益生元作用[140]。

Roseburia[141]是一種利用膳食纖維的腸道細菌，可通過產生丁酸增強腸道屏障。據報道，向小鼠施用玫瑰桿菌可增強腸道固有層中調節性T細胞的分化，并抑制腸道炎癥[142]。如表4所述，據報道，低聚果糖、蘋果衍生的聚合原花青素、海參衍生的硫酸多糖、卡姆卡姆提取物和靈芝菌絲體水提取物可增加腸道菌群中玫瑰桿菌的比例。Roseburia將低聚果糖代謝成果糖，用于生長，但在這個過程中，需要雙歧桿菌產生的乙酸[143]。因此，為了通過攝入低聚果糖來生長薔薇，有必要注意與其他腸道細菌的共生關系以及腸道中短鏈脂肪酸的含量。其他飲食因素，如原花青素、海參衍生的硫酸多糖、卡姆卡姆提取物和靈芝菌絲體，尚未對其對玫瑰桿菌的益生元功能進行研究。

有人認為，普雷沃桿菌的LPS具有較少的磷酸和酰基部分，有助于內毒素活性，從而導致比沙門氏菌的LPS具有更低的TLR4刺激能力[144]。因此，通過增加腸道菌群中普氏桿菌的數量，腸道內容物中的內毒素活性和對腸上皮細胞的損傷可能會降低，從而導致血液LPS水平降低。另一方面，Prevotella生產琥珀酸鹽作為糖代謝的代謝物[145]。也有報道稱，來自腸道細菌的琥珀酸被血清型鼠傷寒沙門氏菌[146]和艱難梭菌[147]利用并促進其生長，這是偽膜性結腸炎的病原體。據報道，琥珀酸通過琥珀酸受體誘發結腸炎，并促進結腸纖維化[148]。此外，據報道，2型糖尿病患者腸道菌群中普氏桿菌的比例與血液LPS水平呈正相關[149]。因此，普氏桿菌比例的增加并不一定對腸道健康產生積極影響。有必要仔細研究普氏桿菌對血LPS水平的影響。）

Clostridium, Escherichia, and Desulfovibrio are bacterial genera that may contribute to the increase of blood LPS levels. Many pathogenic bacteria (such as enterohemorrhagic Escherichia coli, Clostridium botulinum, Clostridium tetani, and Clostridium perfringens), which produce effector proteins or enterotoxins that disrupt epithelial tight junction belong to these genera [150]. In addition, the endotoxin activity of LPS in non-pathogenic Escherichia is also higher than in Bacteroides, and an increased proportion of these Escherichia in enteric flora aggravate colitis [151]. Clostridium species catabolize cholic acid to deoxycholic acid for their growth [152]. It is reported that, in mice, deoxycholic acid increases intestinal permeability through the reduction of goblet cell number, suppression of mucin production, induction of low-grade inflammation, and suppression of tight junction protein (ZO-1) expression [153]. In terms of dietary factors that reduce Escherichia, there are many reports of sulfated polysaccharides (Table 4). We could not find any reports that suggested the direct inhibitory effect of sulfated polysaccharide on growth of Escherichia. On the other hand, it is suggested that Bacteroides, that can be preferentially grown in sulfated polysaccharide feeding, compete with Escherichia in the co-culture assay [127]. In order to elucidate the mechanism by which sulfated polysaccharides reduce the proportion of Escherichia, it is hoped to study focusing on the interaction between gut microbes. Among the dietary factors that reduce Clostridium, procyanidin is reported to decrease the growth of Clostridium in fecal batch culture [154]. The bactericidal activity of methanol extract of nopal against Clostridium has also been reported [155].
Desulfovibrio is a gram-negative, obligate anaerobe, sulfate-reducing bacterium. Desulfovibrio utilizes electrons supplied by the oxidation of lactic acid in the electron transport system of the respiratory chain, uses sulfuric acid as the final electron acceptor, and produces hydrogen sulfide as a metabolite [156]. Desulfovibrio is ubiquitous in the intestines of humans and mice. Of the studies that showed significant changes in the proportion of Desulfovibrio, most studies reported that the proportion was increased associated to the reduction of blood LPS levels (Table 4). However, it is also reported that proportions of Desulfovibrio increased in the colons of patients with ulcerative colitis [157] and has attracted attention as a pathogen of colitis. In addition, Xie et al. reported in mice that the increase of Desulfovibrio in feces was positively correlated with the increase of LPS levels in feces, liver, and blood [45]. Qui et al. reported that ingestion of a high-fat diet in mice increased fecal Clostridium and Desulfovibrio, and oral administration of these bacteria to the normal chow-fed mice increased fecal and blood LPS levels [158]. These reports suggest that Desulfovibrio plays an important role as a source of LPS in the intestine. Desulfovibrio also competes with Anaerostipes caccae for lactic acid produced by Bifidobacterium, and reduces butyric acid production by inhibiting the growth of Anaerostipes caccae [159]. In addition, as the coexistence of Desulfovibrio and Bifidobacterium inhibits the growth of Bifidobacterium [159], this suggests that the amount of acetic acid produced by Bifidobacterium might be also reduced. On the other hand, it has also been reported that oral administration of Desulfovibrio increases the amount of hydrogen sulfide in the intestinal tract and inhibits intestinal peristalsis [160]. Desulfovibrio is thought to play an important limiting role in increasing blood LPS levels by supplying LPS, decreasing intestinal barrier function due to reduction of short-chain fatty acid content, and prolonging retention time of intestinal contents due to inhibition of peristalsis (Figure 2). However, despite Desulfovibrio being an important target for metabolic endotoxemia, few dietary factors have been reported to reduce the proportion of Desulfovibrio (Table 1, Table 2, Table 3 and Table 4).

（

梭菌、大腸桿菌和脫硫弧菌是可能導致血液LPS水平升高的細菌屬。許多致病細菌（如腸出血性大腸桿菌、肉毒梭菌、破傷風梭菌和產氣莢膜梭菌）都屬于這些屬，它們產生破壞上皮緊密連接的效應蛋白或腸毒素[150]。此外，非致病性大腸桿菌中LPS的內毒素活性也高于類桿菌，這些大腸桿菌在腸道菌群中的比例增加會加重結腸炎[151]。梭狀芽孢桿菌將膽酸分解為脫氧膽酸供其生長[152]。據報道，在小鼠中，脫氧膽酸通過減少杯狀細胞數量、抑制粘蛋白產生、誘導低度炎癥和抑制緊密連接蛋白（ZO-1）表達來增加腸道通透性[153]。關于減少大腸桿菌的飲食因素，有許多關于硫酸多糖的報告（表4）。我們沒有發現任何報告表明硫酸多糖對大腸桿菌的生長有直接抑制作用。另一方面，有人認為，在共培養試驗中，可優先在硫酸多糖喂養中生長的類桿菌與大腸桿菌競爭[127]。為了闡明硫酸多糖降低大腸桿菌比例的機制，希望重點研究腸道微生物之間的相互作用。在減少梭菌的飲食因素中，據報道原花青素可減少糞便分批培養中梭菌的生長[154]。還報告了nopal甲醇提取物對梭菌的殺菌活性[155]。

脫硫弧菌是一種革蘭氏陰性專性厭氧硫酸鹽還原菌。脫硫弧菌利用呼吸鏈電子傳輸系統中乳酸氧化提供的電子，使用硫酸作為最終電子受體，并產生硫化氫作為代謝物[156]。脫硫弧菌在人和小鼠的腸道中普遍存在。在顯示脫硫弧菌比例發生顯著變化的研究中，大多數研究報告，該比例的增加與血液LPS水平的降低有關（表4）。然而，也有報道稱，潰瘍性結腸炎患者結腸中脫硫弧菌的比例增加[157]，并作為結腸炎的病原體引起了人們的注意。此外，Xie等人在小鼠中報告，糞便中脫硫弧菌的增加與糞便、肝臟和血液中LPS水平的增加呈正相關[45]。Qui等人報告說，在小鼠中攝入高脂肪飲食會增加糞便中的梭菌和脫硫弧菌，而在正常的周糧喂養小鼠中口服這些細菌會增加糞便和血液中的LPS水平[158]。這些報告表明，脫硫弧菌作為腸內LPS的來源起著重要作用。脫硫弧菌還與仙人掌厭氧菌競爭雙歧桿菌產生的乳酸，并通過抑制仙人掌厭氧菌的生長減少丁酸的產生[159]。此外，由于脫硫弧菌和雙歧桿菌共存抑制了雙歧桿菌的生長[159]，這表明雙歧桿菌產生的乙酸量也可能減少。另一方面，也有報道稱，口服脫硫弧菌會增加腸道內硫化氫的含量，并抑制腸道蠕動[160]。脫硫弧菌被認為在增加血液LPS水平方面發揮了重要的限制作用，通過供應LPS，由于短鏈脂肪酸含量減少而降低腸道屏障功能，以及由于抑制蠕動而延長腸道內容物的保留時間（圖2）。然而，盡管脫硫弧菌是代謝性內毒素血癥的一個重要靶點，但很少有飲食因素能降低脫硫弧菌的比例（表1、表2、表3和表4）。）

Sulforaphane (1-isothiocyanato-4-methylsulfinylbutane) is an isothiocyanate with an N=C=S functional group and is abundant in broccoli (especially the sprout) and other cruciferous vegetables as the precursor glucoraphanin. Sulforaphane is thought to play a role in plant protection through its antimicrobial action [161], induction of programmed cell death of infected tissue [162], and inhibition of insect feeding [163]. On the other hand, in humans and rodents, sulforaphane activates NF-E2-related factor 2 (NRF2), which induces expression of genes expressing antioxidant and detoxication enzymes, including phase II enzymes, and then exerts anti-cancer [164], anti-liver damage [165], and anti-depressive effects [166].
We found that dietary administration of broccoli sprout extract reduced blood LPS levels and attenuated obesity, glucose intolerance, hepatic steatosis, and inflammation in mice fed a high-fat diet [94]. We also reported that the proportion of Desulfovibrionaceae [upper taxa (family) of Desulfobivrio] was positively correlated with blood LPS levels, and that ingestion of broccoli sprout extract reduced Desulfovibrionaceae in cecal contents. Subsequently, Wu et al. also reported that broccoli powder reduced the proportion of Desulfovibrio in the large intestinal contents of mice [167]. They reported that the decrease in Desulfovibrio composition was negatively correlated with the activity of myrosinase-like activity, isothiocyanate content, and NAD(P)H:quinone dehydrogenase 1 (NQO1) in the colonic mucosa. Ingested glucoraphanin is metabolized by myrosinase-like enzymes in enteric bacteria, which then produce sulforaphane [168]. Since sulforaphane enhances NQO1 activity through activation of NRF2 [168], it is suggested that sulforaphane metabolized and formed from glucoraphanin in broccoli sprouts may have an inhibitory effect on Desulfovibrio (Figure 2). Sulforaphane has been reported to exert antibacterial activity against the Proteobacteria (Desulfovibrio belongs this phyla) [169], but its direct effect on Desulfovibrio is not well understood. It is hoped that the mechanism by which sulforaphane decreases the proportion of Desulfovibrio will be elucidated.
5. Conclusions
In this article, we summarized previous reports about the regulation of metabolic endotoxemia through dietary factors, focusing on gut microbiota. Although changes in the composition of Firmicutes and Bacteroides due to excessive fat intake have been reported to contribute to metabolic endotoxemia in many reports, the results differ between studies and between species, and further investigation is needed to find true pathobionts. Moreover, since human epidemiological studies have not found a correlation between fat intake and blood LPS levels, it is necessary to search for dietary factors other than fat that cause metabolic endotoxemia. Regarding dietary factors that improve metabolic endotoxemia, human intervention studies have focused on probiotics, prebiotics, polyphenols and dietary habits, and it has been reported that prebiotics, including oligosaccharides, are effective. On the other hand, few studies have evaluated the effects of dietary intervention on gut flora in humans. The development and popularization of next-generation sequencing has made it possible to comprehensively analyze the “fecal” microbiota in humans. On the other hand, as mentioned above, there are also mucin-adherent bacteria that are thought to be involved in metabolic endotoxemia (e.g., Akkermansia and Bacteroides). In a colitis mouse model, it has been reported that the bacterial flora in the mucin layer exhibits changes from 12 weeks before the onset of colitis, and that the mucin layer was thinned [170]. In this study, changes in the fecal flora occurred at the same time as the onset of colitis, indicating that the bacteria in the mucin layer play an important role in understanding the physiological state of the intestinal tract. However, although it is possible to collect mucin layer samples in animals, it is not easy to do so in humans, due to ethical and technical obstacles. In the future, if a method for collecting the mucin layer in a noninvasive manner is established in humans, the research field of metabolic endotoxemia can be further advanced. Then, it is expected that we will comprehensively understand the relationship between dietary factors, dysbiosis, and metabolic endotoxemia in humans by conducting human intervention studies and epidemiological studies with dietary surveys, gut microbiota analysis using next-generation sequencers and evaluation of blood LPS levels.

（萊菔硫烷（1-異硫氰酸酯-4-甲基亞磺酰丁烷）是一種具有N=C=S官能團的異硫氰酸酯，在西蘭花（尤其是芽菜）和其他十字花科蔬菜中大量存在，其前體為葡糖苷。蘿卜硫素被認為通過其抗菌作用[161]，誘導受感染組織的程序性細胞死亡[162]，以及抑制昆蟲取食[163]，在植物保護中發揮作用。另一方面，在人類和嚙齒類動物中，萊菔硫烷激活NF-E2相關因子2（NRF2），誘導表達抗氧化酶和解毒酶（包括II期酶）的基因表達，然后發揮抗癌[164]、抗肝損傷[165]和抗抑郁作用[166]。

我們發現，在喂食高脂飲食的小鼠中，西蘭花芽提取物的飲食給藥降低了血LPS水平，減輕了肥胖、葡萄糖不耐受、肝脂肪變性和炎癥[94]。我們還報告了脫硫弧菌科[脫硫弧菌屬的上層分類群（科）]的比例與血液LPS水平呈正相關，攝入西蘭花芽提取物可降低盲腸中脫硫弧菌科的含量。隨后，Wu等人還報告說，西蘭花粉降低了小鼠大腸內容物中脫硫弧菌的比例[167]。他們報道，結腸粘膜中脫硫弧菌成分的減少與芥子酶樣活性、異硫氰酸鹽含量和NAD（P）H:醌脫氫酶1（NQO1）的活性呈負相關。攝入的葡萄糖苷由腸道細菌中類似芥子酶的酶代謝，然后產生蘿卜硫素[168]。由于萊菔硫烷通過激活NRF2[168]來增強NQO1活性，這表明萊菔硫烷在西蘭花芽中代謝并由格拉芬形成，可能對脫硫弧菌有抑制作用（圖2）。據報道，萊菔硫烷對變形菌（脫硫弧菌屬該門）[169]具有抗菌活性，但其對脫硫弧菌的直接作用尚不清楚。希望能夠闡明萊菔硫烷降低脫硫弧菌比例的機理。

5.結論

在這篇文章中，我們總結了以前關于通過飲食因素調節代謝性內毒素血癥的報道，重點是腸道微生物群。盡管在許多報告中，由于脂肪攝入過多而導致的厚壁菌和類桿菌成分的變化已被報道為導致代謝性內毒素血癥，但研究結果在不同的物種之間和不同的物種之間存在差異，需要進一步的調查以找到真正的致病菌。此外，由于人類流行病學研究尚未發現脂肪攝入與血LPS水平之間的相關性，因此有必要尋找導致代謝性內毒素血癥的飲食因素，而非脂肪。關于改善代謝性內毒素血癥的飲食因素，人類干預研究的重點是益生菌、益生元、多酚和飲食習慣，據報道，益生元（包括低聚糖）是有效的。另一方面，很少有研究評估飲食干預對人體腸道菌群的影響。下一代測序技術的發展和普及使得全面分析人類“糞便”微生物群成為可能。另一方面，如上所述，還有粘蛋白粘附細菌被認為與代謝性內毒素血癥有關（如阿克曼菌和類桿菌）。在結腸炎小鼠模型中，據報道，從結腸炎發病前12周開始，粘蛋白層中的菌群發生變化，粘蛋白層變薄[170]。在這項研究中，糞便菌群的變化發生在結腸炎發病的同時，這表明粘蛋白層中的細菌在了解腸道生理狀態方面起著重要作用。然而，盡管可以在動物身上采集粘蛋白層樣本，但由于道德和技術障礙，在人類身上采集粘蛋白層樣本并不容易。未來，如果能在人類身上建立一種非侵入性收集粘蛋白層的方法，代謝性內毒素血癥的研究領域將得到進一步的發展。然后，通過開展人類干預研究和流行病學研究，包括飲食調查、使用下一代測序儀進行腸道微生物群分析以及評估血液LPS水平，我們有望全面了解人類飲食因素、生態失調和代謝性內毒素血癥之間的關系。）

上面內容來自【6】

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下面摘自【5】

Particularly, the coccus strain Pediococcus pentosaceus(戊糖片球菌菌株) eliminates LPS to 43%

上面內容來自【5】

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高脂飲食=生酮飲食 嗎？

不等于，高脂飲食中采用的都是劣質脂肪。

生酮飲食采用的是優質脂肪。[8]

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隨著人的衰老，腸道菌群發生一定程度的演替，即擬桿菌門和雙歧桿菌等厭氧菌數量的減少和厚壁菌門數量的增多。[7]

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附錄(常用概念)

概念	解釋
FODMAP	FODMAP（可發酵性的寡糖、雙糖、單糖以及多元醇）是食品中的一類短鏈碳水化合物及糖醇，高FODMAP飲食可加劇腸易激綜合征的癥狀，Journal of Clinical Investigation[IF：12.784]近期發表的由華人學者團隊開展的研究對其背后的機制進行了探討，發現高FODMAP飲食可使腸道菌群失調，腸內高LPS水平似乎是誘導腸道病癥的主因，而食用低FODMAP飲食可降低LPS水平，從而緩解IBS癥狀。值得關注的研究，推薦閱讀。
LPS	Lipopolysaccharides
益生菌	益生菌是一類有利于維持腸道菌群穩態的活的微生物制劑，通過補充一種或多種對人體有益的細菌(如雙歧桿菌、乳酸菌等)從而起到穩定腸道菌群的作用。
益生元	益生元是一類人體較難消化的成分，可以促進結腸中部分有益菌的生長，對人體產生積極的生理作用。
合生元	合生元是一類將益生菌和益生元聯合使用的制劑。腸內營養(enteral nutrition，EN)是指通過經口攝食或管飼途徑補充營養素的支持性治療。

LPS的營養支持（沒有驗證）:

黃酮類

硫辛酸

南非醉茄

蝦青素

小檗堿（黃連素）

越橘

生物素

洋甘菊（芹菜素）

丁香

姜黃素

表沒食子兒茶素沒食子酸酯（EGCG）

魚油（DHA，EPA和DPA）

亞麻油（α-亞麻酸）

葉酸

谷氨酰胺

綠茶?

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Psoriatics have been found to have deficient bile acid production in the liver. One role of bile acids is to break down fats and endotoxins.（服用膽汁酸治療銀屑病）[13]
We don't have enough studies into the effect of antibiotics on psoriasis, but at least one study found that psoriasis could be cleared with a long-term regimen of azithromycin.（長期服用阿奇霉素）[13]

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荷蘭Winclove益生菌公司開發針對銀屑病的補充劑(預計于2020年開始，預計需要大約12-18個月才能完成)稱為AxisBiotix，

同時要求減少酒精攝入或補充ω3脂肪酸和維生素D，適當攝入綠茶[14]

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炎癥性腸病和/或克羅恩病與銀屑病之間可能存在聯系。克羅恩病患者會出現皮膚癥狀，包括銀屑病樣斑塊，一項研究表明，通常用于治療銀屑病的藥物對克羅恩病也有效?[15]

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The causes of leaky gut
Evidence suggests many factors can contribute to leaky gut, including stress; eating pesticide-laden foods; and an overgrowth of bacteria in the small intestine (SIBO). This overgrowth can be caused by long-term use of antacids, antibiotic use, and eating a standard Western diet full of processed foods.（少吃加工食品,）

Leaky gut is controversial
Readers should keep in mind that while a growing number of physicians believe leaky gut is the underlying cause of many medical conditions, many do not. Leaky gut and its possible connection to arthritic disease is not part of most standard medical school curriculums.(目前腸漏理論依然有爭議并且在大部分教科書上看不見)[16]

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Together with the reduced F. prausnitzii levels, the psoriasis patients had a significantly higher abundance of E. coli. It was apparent that patients with concomitant IBD and psoriasis had the greatest decrease of ?F. prausnitzii and increase of E. coli.(銀屑病患者體內的大腸桿菌豐度明顯較高，且prausnitzii桿菌水平降低。很明顯，伴有IBD和銀屑病的患者的prausnitzii桿菌減少最多，大腸桿菌增加最多。)[17]

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普雷斯特博士強調，偶爾吃“治療食品”是可以的，但它們不應該構成你飲食的大部分。

克利夫蘭診所稱，添加糖、飽和脂肪、反式脂肪、ω-6脂肪酸和精制碳水化合物也會增加炎癥。一些研究表明，如果你患有牛皮癬并且對麩質過敏，那么食用無麩質飲食可以減少牛皮癬并減少發作。

你應該多吃什么食物？

普雷斯特說，如果你患有銀屑病，消炎食品，如水果、蔬菜、植物蛋白、魚、堅果和種子，應該占你飲食的大部分。

她說：“讓你的盤子里的植物向前生長，至少一半的盤子里裝滿水果和蔬菜，并選擇一小部分植物蛋白或瘦肉動物蛋白。”。“水果和蔬菜是自然界的消炎劑，因為它們富含抗氧化劑和植物化學物質。”

她補充說，將飽和脂肪和反式脂肪換成更健康的選擇，如橄欖油、鱷梨、冷水魚、大豆和堅果。添加醋、香草和香料代替添加的鹽，選擇低脂乳制品。

相關：地中海飲食中你可以吃的110種食物

地中海飲食包括大量水果、蔬菜、健康脂肪和瘦肉，具有抗炎作用，可以減少皮膚上的牛皮癬。

普雷斯特博士說，水果、蔬菜和全谷物也富含纖維，纖維有助于喂養健康的腸道細菌。益生菌，包括酸奶和發酵食品，益生元，如水果和蔬菜，也能改善腸道細菌。保持健康的腸道細菌可以減少炎癥，并可以減少銀屑病的癥狀。

如果你的飲食沒有達到應有的健康水平，那么改變永遠不會太遲。普雷斯特博士說，健康飲食的改變可以在幾周內改善你的銀屑病癥狀。[18]

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In a 2014 paper in the Journal of Gastroenterology, scientists created and visualized the creation of inflammation and intestinal gaps (i.e. leaky gut) in IBS patients after the introduction of wheat, yeast, milk, and soy.8.

In addition to that, the typical Western diet, one that is high in fat, refined sugar, and low in fiber, consistently increases intestinal permeability in animal models7.

Fructose solutions can produce the same result, which may be why those with “sensitive tummies” often respond well to low FODMAP diets. We also know that certain drugs, like antibiotics and NSAIDs, disrupt the normal microbiome and affect permeability.(在《胃腸病學雜志》2014年的一篇論文中，科學家們創造并可視化了炎癥和腸道間隙（即腸道滲漏）的產生在腸易激綜合征患者中引入小麥、酵母、牛奶和大豆后。

除此之外，典型的西方飲食，即高脂肪、高糖和低纖維飲食，在動物模型中持續增加腸道通透性7。

果糖溶液也能產生同樣的結果，這可能就是為什么那些“敏感肚子”的人通常對低FODMAP飲食反應良好的原因。我們還知道，某些藥物，如抗生素和非甾體抗炎藥，會破壞正常的微生物群并影響滲透性。)[19]

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?自兩個患者組的樣本均顯示糞球菌物種豐度相對減少，而來自PsA患者的樣本也表現為阿克曼菌、瘤胃球菌和假丁酸菌顯著減少。PsA患者糞便樣本上清液顯示sIgA水平升高，RANKL水平降低。脂肪酸分析顯示PsA患者和銀屑病患者糞便中己酸鹽和庚酸鹽含量較低。[20]

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?later work by Norrlind et al. successfully correlated streptococcal pharyngitis (as
evidenced by pharyngeal swab culturing and serology) with guttate psoriasis as well as exacerbations
of stable chronic plaque psoriasis(Norrlind等人后來的研究成功地關聯了鏈球菌性咽炎（as）

咽部拭子培養和血清學）證實為點滴狀銀屑病以及惡化

穩定型慢性斑塊型銀屑病[21]

Interestingly, Chen et al. demonstrated that mice fed Lactobacillus pentosus developed a milder
form of imiquimod-induced psoriasis when compared to mice fed with a vehicle control [65].
Moreover, it has been shown that mice fed with Lactobacillus pentosus have suppressed psoriasis-related
pro-inflammatory and Th17-associated cytokines, such as TNF-α, IL-6, IL-23, IL-17A, IL-17F,
and IL-22 (有趣的是，Chen等人證明了喂食戊糖乳桿菌的小鼠產生了更溫和的反應

與喂食溶媒對照的小鼠相比，咪喹莫特誘發的銀屑病的形式[65]。

此外，研究表明，喂食戊糖乳桿菌的小鼠可抑制銀屑病相關疾病

促炎和Th17相關細胞因子，如TNF-α、IL-6、IL-23、IL-17A、IL-17F，

和IL-22[66]。乳酸桿菌在人類銀屑病患者中的直接作用仍需進一步研究

接受調查。)

After adhering to a gluten-free diet for three months, patients were noted to
have a significantly decreased dermal Ki-67+ cell population (an indicator of cell proliferation) in
lesional skin.(堅持無麩質飲食)[21]

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銀屑病患者腸道菌群多樣性減少。[22]

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?It is unknown whether increased gut permeability is an early event in the pathogenesis of psoriasis or the consequence of the disease.（不清楚腸道通透性增加是銀屑病的原因還是致病結果）[23]

However, the results were heterogeneous, with some patients presenting significantly affected intestinal integrity, and others showing a properly functioning gut barrier.(一些銀屑病患者的腸道功能異常，其余患者正常)[23]

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有人服用了Alflorex益生菌后銀屑病痊愈[24]

另外有人補充維生素D，鎂以及omega3[24]

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One study found patients who received a daily oral dose of Lactobacillus paracasei NCC2461 exhibited decreased skin sensitivity, improved barrier function, and improved efficiency in preserving skin moisturizing agents. In a murine model, a milder form of psoriasis was observed following administration of Lactobacillus pentosus. Lactobacillus pentosus has been shown to suppress psoriasis associated pro-inflammatory Th17-associated cytokines.? (項研究發現，每天口服劑量為 副干酪乳桿菌 NCC2461降低了皮膚敏感性，改善了屏障功能，提高了保濕劑的保存效率。在小鼠模型中 輕度銀屑病 服用戊糖乳桿菌后觀察到。戊糖乳桿菌 已經證明可以抑制銀屑病相關的促炎性Th17相關細胞因子)[25]

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In psoriasis, the deposit of excess antigens in the skin is thought to be one possible trigger for the development of a plaque.（皮膚中存在過量抗原的沉積）

Focus on anti-inflammatory foods including wild fish and other sources of omega-3 fats, red and purple berries (rich in polyphenols), dark green leafy vegetables, orange sweet potatoes, nuts and seeds. Add anti-inflammatory herbs and spices, including turmeric (a source of anti-inflammatory curcumin), garlic, oregano, ginger, rosemary, holy basil and turmeric, as well as green tea to your daily diet. Eliminate inflammatory foods such as refined, omega-6 and inflammatory oils including corn, soy and safflower oils.(關注抗炎食品，包括野生魚類和其他來源的歐米茄-3脂肪、紅色和紫色漿果（富含多酚）、深綠色葉菜、橙色甘薯、堅果和種子。在日常飲食中添加抗炎草藥和香料，包括姜黃（一種抗炎姜黃素的來源）、大蒜、牛至、生姜、迷迭香、羅勒和姜黃，以及綠茶。消除發炎性食物，如精制、歐米茄-6和發炎性油脂，包括玉米油、大豆油和紅花油。)

Remove food sensitivities

A review of research from 2008 strongly recommended gluten-free for people with this condition and celiac disease, but not for people without a celiac diagnosis or gluten sensitivity.(去除麩質飲食)[26]
?

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Gut microbiota are mainly composed of four phyla, namely, Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria (Qin et al., 2010). The human gut microbiota is dominated by only 2 of them: the Bacteroidetes and the Firmicutes (??98%), whereas Actinobacteria, Proteobacteria, and others are present in minor proportions (Eckburg et al., 2005). Gut microbiota provides its host with a physical barrier to pathogens by competitive exclusion, such as occupation of attachment sites, consumption of nutrient, and production of antimicrobial substances.[27](人類腸道有一個主要的微生物定殖表面，富含可被微生物用作營養物質的分子，使其成為定植的首選場所，因此定植最嚴重的器官是胃腸道；據估計，僅結腸就含有人體內70%以上的微生物（Ley等人，2006年）。腸道微生物群主要由四個門組成，即厚壁菌門、擬桿菌門、放線菌門和變形菌門（Qin等人，2010）。人類腸道微生物群僅由兩種菌群控制：擬桿菌和厚壁菌（98%），而放線菌、變形菌和其他菌群的比例較小（Eckburg et al.，2005）。腸道微生物群通過競爭性排斥為宿主提供了抵抗病原體的物理屏障，如附著位點的占據、營養物質的消耗和抗菌物質的產生。它還刺激宿主產生各種抗菌化合物。)

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She also consumed more prebiotic-rich foods like dandelion greens and Jerusalem artichoke. (蒲公英綠和耶路撒冷朝鮮薊)[28]

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Low-grade inflammation is alarmingly widespread, affecting about 40% of people in Western countries. 【29】

One aspect of diet that is particularly heinous is sugar, a well-known pro-inflammatory agent. Anything with added sugar should be avoided, as should all refined carbohydrates — white rice, bread, pasta, pastries, etc. Inflammatory skin conditions like acne are highly prevalent in Western countries, something that has been attributed to the abundance of carbohydrates in the diet.

Also on the “avoid” list are refined cooking vegetable oils: corn, soya, sunflower oils. These omega-6-rich vegetable oils are notoriously pro-inflammatory and should be avoided as much as possible. When you cook your food in oil, use coconut oil, butter, or extra virgin olive oil, and avoid processed foods — they nearly always contain refined vegetable oils.
“Elevated n-6 intakes are associated with an increase in all inflammatory diseases, which is to say virtually all diseases.”
Next, aim for a diet loaded with both probiotics and prebiotics.
Fermented foods are a good source of probiotics. Good examples include live natural yogurt, kefir, sauerkraut, and miso.
Probiotics are naturally anti-inflammatory, so feed them well with prebiotics.
Some of the best sources of prebiotics are onions, leeks, garlic, chicory root, coconut, carrots, asparagus, yams, and the cruciferous vegetables broccoli, cabbage, and sprouts.
The role of the gut microbiome in influencing the health of the whole body has been the focus of much recent research, but it is not a new discovery. As long ago as 1911, the gastroenterologist Milton H. Mack wrote that acne and eczema could be traced to the digestive tract, which he called “this fountainhead of diseases”. Today it’s called the gut-skin axis. Listen to what it’s trying to tell you.

（飲食中特別令人發指的一個方面是糖，一種眾所周知的促發炎劑。任何添加糖的食物都應該避免，所有精制碳水化合物都應該避免，如白米、面包、面食、糕點等。在西方國家，痤瘡等發炎性皮膚病非常普遍，這是由于飲食中含有豐富的碳水化合物。

同樣在“避免”清單上的還有精制食用植物油：玉米油、大豆油、葵花籽油。這些富含ω-6的植物油是出了名的促發炎劑，應該盡量避免使用。當你用油烹飪食物時，使用椰子油、黃油或特級初榨橄欖油，避免加工食品——它們幾乎總是含有精制植物油。

n-6攝入量的增加與所有炎癥性疾病（也就是說幾乎所有疾病）的增加有關

下一步，目標是飲食中同時含有益生菌和益生元。

發酵食品是益生菌的良好來源。好的例子包括天然酸奶、開菲爾、酸菜和味噌。

益生菌具有天然的抗炎作用，因此給它們添加益生元。

一些最好的益生元來源是洋蔥、韭蔥、大蒜、菊苣根、椰子、胡蘿卜、蘆筍、山藥以及十字花科蔬菜西蘭花、卷心菜和芽菜。

腸道微生物組在影響全身健康方面的作用一直是最近許多研究的焦點，但這并不是一個新發現。早在1911年，胃腸病學家Milton H.Mack就寫道，痤瘡和濕疹可以追溯到消化道，他稱之為“疾病的源頭”。今天，它被稱為腸道皮膚軸。聽聽它想告訴你什么。）

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In both groups, Firmicutes were the most common detected phylum followed by Bacteroidetes and finally Actinobacterial phyla. High statistically significant difference was reported for the Firmicutes/ Bacteroidetes ratio between the psoriasis patients and the control group and showed statistically significant positive correlations with PASI. Actinobacterial count was significantly higher in the control group than in psoriasis patients and showed statistically significant negative correlations with PASI. It is believed that, there are fractions of the gut microbiota with the ability to counteract inflammation (Bacteroidetes and Actinobacterial), and others that are more prone to induce inflammation (Firmicutes) and the disturbed microbiome ratio may be the cause for inducing psoriasis.

(在這兩組中，厚壁菌門是最常見的檢測門，其次是擬桿菌門，最后是放線菌門。銀屑病患者和對照組之間的厚壁菌/擬桿菌比率存在高度的統計顯著性差異，并顯示出與PASI的統計顯著正相關。對照組的放線菌計數顯著高于銀屑病患者，且與PASI呈統計學顯著負相關。據認為，腸道微生物群中有一部分具有抵抗炎癥的能力（類桿菌和放線桿菌），而其他部分更容易誘發炎癥（厚壁菌群），并且紊亂的微生物群比例可能是誘發銀屑病的原因。)[30]

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These findings reveal that patients with psoriatic skin and joint disease should consider changing to a healthier dietary pattern[31]

######################下面是論文[32]的百度翻譯#######################

表1。銀屑病皮膚與健康對照組的細菌豐度比較

銀屑病的低豐度

銀屑病高豐度

表皮細菌[10,12]

痤瘡表皮菌[11]

鏈球菌[10,14]

葡萄球菌[14]

金黃色葡萄球菌[11]

棒狀桿菌[14]

益生菌如何幫助牛皮癬？

益生菌是活的微生物，能夠通過恢復微生物組的平衡而帶來許多健康益處。越來越多的研究關注益生菌在預防和治療某些皮膚病（如特應性皮炎）中的應用。[15]盡管很少有研究專門關注益生菌在銀屑病中的應用，從理論上講，益生菌療法可能通過促進減少銀屑病炎癥的良好細菌來平衡人的促炎和抗炎免疫功能。

哪些益生菌有助于治療牛皮癬？

益生菌中最常見的微生物有：[16]

乳酸桿菌

雙歧桿菌

腸球菌

表皮菌

布拉迪酵母菌

許多關于口服益生菌（包括乳酸桿菌和雙歧桿菌）的研究表明，這些益生菌有助于預防和治療過敏性皮炎等炎癥性皮膚病。[17]盡管關于哪些益生菌菌株有助于特異性治療銀屑病的研究有限（表2），一項針對26名銀屑病患者的研究比較了口服益生菌嬰兒雙歧桿菌25634對銀屑病促炎標志物的影響，發現與安慰劑和基線相比，治療8周后C反應蛋白和腫瘤壞死因子（TNF）-α水平顯著下降。[18]

此外，一項體內研究發現，口服戊糖乳桿菌GMNL-77可顯著降低促炎細胞因子mRNA水平（IL-6、TNF-a和IL-23/IL-17A），并減少咪喹莫特誘導的銀屑病樣炎癥小鼠的皮膚紅斑和鱗屑。[19]

一例膿皰性銀屑病患者對類固醇和甲氨蝶呤無反應的病例報告顯示，在6個月內每天口服三次產孢乳桿菌治療其急性病變在2周內無新病變復發。[20]

一項針對1206名銀屑病患者的飲食習慣、干預措施和改變的調查發現，40.6%的受調查患者報告在飲食中添加益生菌后情況有所改善或完全消失。[21]

表2。銀屑病使用益生菌的臨床證據總結

著者

研究類型

調查結果

Groeger等人，2013[18]

RCT*

26名患者在8周后口服嬰兒雙歧桿菌25634可降低CRP和TNF-α

陳等，2017[19]

前瞻性對照研究

口服戊糖乳桿菌GMNL-77可降低咪喹莫特治療小鼠的IL-6、TNF-a和IL-23/IL-17A

Vijayashankar等人，2012[20]

病例報告

口服產孢乳桿菌可減少膿皰性銀屑病，并在6個月內預防復發

Afifi等人，2017[21]

調查

在1206例銀屑病患者中，40.6%的患者在飲食中添加益生菌后癥狀有所改善或完全消失[32]

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In the study, New York University researchers found that psoriatic arthritis sufferers had lower levels of specific types of bacterium including?Akkermansia,?Ruminococcus, and?Pseudobutyrivibrio. Normally, these bugs help keep your immune system under control, but when levels dip too low, all bets are off.(紐約大學的研究人員發現銀屑病性關節炎患者的特定類型的細菌水平較低，包括阿克曼菌、瘤胃球菌和假丁酸菌。)[33]

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Interestingly, night-shift workers exhibited not only an increase in severity of psoriatic flares, but also an increased incidence of psoriasis, suggesting that shifting the circadian rhythm (i.e., sleep and diet) may be a risk factor for psoriasis[52](夜班工人銀屑病容易加重)

Previous studies have reported the positive effects of low-energy diets, vegetarian diets, formula diet weight loss programs, gluten-free or very low-calorie carbohydrate-free diet.

For instance, 12-O-tetradecanoylphorbol-13-acetate (TPA), a known inflammatory signal transducer, can induce psoriasis-like skin lesions in mice, while lesions and proinflammatory cytokine expression were significantly reduced in TPA-induced psoriasis by tangerine-derived nutrient flavonoids: Nobiletin (Nob) and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)[67]. In addition, obesity, a result of poor nutrition, has been shown to exacerbate the severity of psoriasiform dermatitis in imiquimod-induced rodent models[68]. (橘子衍生的營養類黃酮（Nobiletin，Nob）和5-羥基-6,7,8,3′，可顯著降低損傷和促炎細胞因子的表達)

Previous research has shown evidence for biochemical skin barrier restoration through topical administration of solenopsin, a compound of fire ant venom chemically similar to ceramides, and its derivates by reducing inflammatory markers and improving acanthosis in KC-Tie2 mice, an established rodent-model of psoriasis[69].(提到了螺旋藻毒素)

Up to 10% of patients with inflammatory bowel disease (IBD) are diagnosed with psoriasis[74]. Patients with psoriasis have a 3-fold higher risk of developing Crohn’s disease as compared to the general population; and Crohn’s disease patients have a 7-fold higher risk of developing psoriasis[75]. Recently, Scher et al[76], using pyrosequencing, found that patients with psoriatic arthritis and patients with skin psoriasis had a decreased bacterial diversity and a reduced relative abundance of some bacterial taxa such as Akkermansia, Ruminococcus, and Pseudobutyrivibrio, as compared to healthy controls. Among the risk factors for psoriatic diseases summarized in Table 1, overall, the alteration of gut microbiota may translate into physiological consequences including poor regulation of intestinal immune responses that may then affect distant organ systems[77-85]. Given the gut microbiome’s influence on the Gut-Skin axis, probiotic supplementation may have a promising role in the management of psoriatic patients. On this point, Gueniche et al[77], in a randomized double-blind placebo-controlled clinical study, showed that oral supplementation with the probiotic strain Lactobacillus paracasei decreased skin sensitivity and increased the rate of barrier function recovery.(高達10%的炎癥性腸病（IBD）患者被診斷為銀屑病[74]。銀屑病患者發生克羅恩病的風險是普通人群的3倍；克羅恩病患者患銀屑病的風險高7倍[75]。最近，Scher等人[76]利用焦磷酸測序發現，與健康對照組相比，銀屑病關節炎患者和皮膚銀屑病患者的細菌多樣性降低，某些細菌類群（如阿克曼菌、瘤胃球菌和假丁酸菌）的相對豐度降低。在表1總結的銀屑病風險因素中，總的來說，腸道微生物群的改變可能轉化為生理后果，包括腸道免疫反應調節不良，從而影響遠端器官系統[77-85]。鑒于腸道微生物組對腸道-皮膚軸的影響，益生菌補充可能在銀屑病患者的治療中發揮有希望的作用。在這一點上，Gueeniche等人[77]在一項隨機雙盲安慰劑對照臨床研究中表明，口服補充益生菌菌株副干酪乳桿菌可降低皮膚敏感性并提高屏障功能恢復率。)[34]

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One study showed that oral administration of Lactobacillus pentosus GMNL-77 (as a probiotic), in a
mouse model of psoriasis, reduced tumor necrosis factor-α and IL-23–IL-17 axis cytokines, which was
associated with significant decreased erythematous scaling lesions and epidermal thickening in
comparison to untreated control mice [26]. Another study showed that Lactobacillus rhamnosus
suppressed the expression of TNF?α, IL?6, and proinflammatory cytokines in the IL?23/IL?17 cytokine axis
[27]. Our findings are in agreement with the previous study on severe pustular psoriasis cases; that did not
respond to steroids, dapsone, and methotrexate. However, after beginning probiotic supplementation
(Lactobacillus sporogenes) three times per day, the psoriatic patients showed significant clinical
improvement within two weeks with almost complete remission after four weeks [29]. In a placebocontrolled study of psoriasis patients, Bifidobacterium Infantis supplementation for eight weeks led to
significantly decreased plasma levels of inflammatory C-reactive protein and TNF?α in comparison with
the placebo group [20]. The authors proposed that in response to probiotic supplementation, levels of the
beneficial microbial inhabitant of the large intestine increased. These species are much less abundant in
the gut of psoriatic patients than in healthy ones. Butyrate, an SCFA that provides energy for colonocytes,
reduces oxidative stress, and exerts anti-inflammatory action by triggering regulatory T cells, thereby
conferring immune tolerance beyond the GI system（戊糖乳桿菌+丁酸鹽）[35]

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The Probiotic Plan
“One of the reasons many chronic diseases, including autoimmune diseases, are on the rise is increased intestinal permeability, or leaky gut,” Dr. Sinatra says. “This can lead to immune dysfunction, setting the stage for autoimmune diseases to develop and progress.” (Note: Leaky gut is a concept credited more by alternative-medicine practitioners than by mainstream doctors.)(飲食+草藥+補充劑需要一起上)

Picking the Best Probiotic to Take
When you’re searching for a probiotic, look at the label to see the number of colony-forming units (CFUs). “While the optimal probiotic dose remains unknown, it’s generally recognized in the medical community that formulas should contain at least 100 million CFUs to be effective,” Sinatra says. “But doses can be as high as hundreds of billions. And for formulas that list their strength in milligrams, you want to look for one that contains at least 350 milligrams of probiotics.”

There are a number of different kinds of probiotics to choose from. Some people benefit from taking lactic-acid probiotics like Lactobacillus or Bifidobacterium, while others do better with yeast-derived probiotics like Saccharomyces boulardii or soil-based organisms like bacillus. For some people, a combination of all three probiotic types is ideal. ?

Remember that probiotics sold as dietary supplements are not regulated by the U.S. Food and Drug Administration (FDA). To ensure purity, read labels carefully, look for supplements that are rigorously screened for contaminants, and consult with your healthcare team.(乳酸菌或雙歧桿菌等乳酸益生菌中獲益，而其他人則從布拉迪酵母菌等酵母源性益生菌或芽孢桿菌等土壤微生物中獲益,并且至少攝入一萬單位)

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If you discover that you have SIBO or dysbiosis, it’s very important to balance your microbiome using antimicrobial herbs, antibiotics, probiotics, prebiotics and more. This, in turn, will help to regulate your immune system!(如果你發現自己患有SIBO或生態失調，使用抗菌藥草、抗生素、益生菌、益生元等來平衡你的微生物群是非常重要的。)

Regularly consuming fermented foods like kimchi, sauerkraut, yogurt and kefir is a great way to get these helpful bacteria into your system. (35, 36)發酵食品和益生菌飲料

You can also take a probiotic supplement to get these beneficial bacteria if you’re not a fan of fermented foods. (37)

多吃發酵食品或者是益生菌

BOOSTING PREBIOTIC AND FIBER INTAKE
Healthy gut bacteria use prebiotics and fiber to survive, grow, thrive and make SCFAs. (38) Increasing fiber intakes can boost their levels and function in the gut within just a few days! (39)

Easy ways to increase fiber intake include loading up on fiber-rich foods, such as fruits and vegetables, or taking a fiber supplement. (37)

GETTING ENOUGH EXERCISE
Studies show moderate aerobic exercise can increase the health of your gut bacteria. (40) The introduction of a regular exercise routine has also been shown to be useful in easing psoriasis symptoms. ?(41, 42, 43)

SHIFTING TO A WHOLE FOODS DIET
Study after study shows that a western style diet rich in calories, fat, simple sugars, and salt and low in fruits and vegetables is harmful to healthy gut bacteria, while traditional diets rich in whole foods help these bacteria grow. (47, 48, 49, 50)

Multiple studies also show that putting individuals with psoriasis on a whole-food diet can improve their symptoms. (41, 42, 43)

THE IMPACT OF DIET ON THE IMMUNE SYSTEM
Diet plays a crucial role in regulating a healthy immune system and controlling psoriasis.

增加益生元和纖維的攝入有利于SCFA

加工食品轉向全食品不僅可以提高纖維攝入量、健康腸道細菌數量、SCFA水平和組胺水平，還可以直接抑制Th17細胞。[37]

Advanced Glycation End Products (AGEs)
Advanced glycation end products (AGEs) form when foods are heated to extreme temperatures, making them a common molecule found in broiled or fried foods like chips, french fries, chicken nuggets, fish sticks, etc. (56, 57)

Similar to how SCFAs and histamine help Treg cells mature, AGEs have been found to help inflammation-promoting Th17 cells mature. (58) This suggests that eating lots of fried junk food can increase the number of damaging Th17 cells.

TH17 FUNCTION AND WHOLE FOODS
On the other hand, replacing junk food with whole foods can help to reduce the damage from Th17 cells.

Potassium
One nutrient rich in many whole foods that may play an important role in regulating immune function is potassium.

High levels of potassium trigger the kidneys to produce a group of molecules called glucocorticosteroids. (59)

These molecules are natural steroids that work just like the drugs doctors prescribe. They are powerful inhibitors of inflammatory chemicals. (60)

Bioactive Phytonutrients
Many whole plant foods contain phytonutrients that have helpful health benefits. Some of these benefits include preventing the effects of inflammatory chemicals on the body. (61, 62, 63)

Some of these anti-inflammatory phytonutrients have powerful effects against inflammatory chemicals known to be important in damaging psoriatic skin.

For example, there is a phytonutrient in turmeric root called curcumin that blocks the effects of the inflammatory chemical TNF-alpha, which plays a major role in promoting psoriasis. (64, 65) In fact, curcumin blocks TNF-alpha nearly as well as drugs we designed to block it. (66)

In addition to the anti-inflammatory nature of phytonutrients, polyphenols (a type of phytonutrient) also boost the health of your microbiome. If you’d like to learn more about that process, check out my article on the topic here.

Antioxidants
As their name suggests, antioxidants block the effects of oxidants.

Since one of the key chemicals Th17 cells use to damage skin cells are oxidants (called reactive oxygen species (ROSs)), antioxidants from fruits, vegetables, nuts, seeds, teas and spices may be helpful in reducing psoriasis symptoms. (18, 67, 68, 69, 70)

THE BOTTOM LINE:
The evidence suggests that a whole food diet rich in foods that help promote a healthy microbiome may help prevent and reduce the symptoms of psoriasis and other autoimmune diseases.

(晚期糖基化終產物（AGEs）

高級糖基化終產物（AGEs）是在食物加熱到極端溫度時形成的，使其成為薯條、薯條、雞塊、魚棒等燒烤或油炸食品中常見的分子。（56,57）

與SCFA和組胺如何幫助Treg細胞成熟相似，AGEs也被發現有助于炎癥促進Th17細胞成熟。（58）這表明吃大量油炸垃圾食品會增加破壞性Th17細胞的數量。

TH17功能與全食

另一方面，用全脂食品代替垃圾食品有助于減少Th17細胞的損傷。

鉀

鉀是許多全食中富含的一種營養素，可能在調節免疫功能方面發揮重要作用。

高水平的鉀觸發腎臟產生一組稱為糖皮質激素的分子。(59)

這些分子是天然類固醇，就像醫生開的藥一樣有效。它們是炎癥化學物質的強力抑制劑。(60)

生物活性植物營養素

許多全植物食物含有對健康有益的植物營養素。其中一些好處包括防止炎癥化學物質對身體的影響。(61, 62, 63)

這些抗炎植物營養素中的一些對炎癥化學物質具有強大的作用，已知這些化學物質對銀屑病皮膚的損害很重要。

例如，姜黃根中有一種叫做姜黃素的植物營養素，它可以阻止炎癥化學物質TNF-α的作用，TNF-α在促進銀屑病方面起主要作用。（64，65）事實上，姜黃素對TNF-α的阻斷作用幾乎和我們設計的阻斷TNF-α的藥物一樣好。(66)

除了植物營養素的抗炎性質外，多酚（一種植物營養素）還可以促進微生物群的健康。如果你想了解更多關于這個過程的信息，請查看我在這里的文章。

抗氧化劑

顧名思義，抗氧化劑可以阻止氧化劑的作用。

由于Th17細胞用來損害皮膚細胞的關鍵化學物質之一是氧化劑（稱為活性氧物種（ROSs）），因此來自水果、蔬菜、堅果、種子、茶和香料的抗氧化劑可能有助于減輕銀屑病癥狀。(18, 67, 68, 69, 70)

底線是：

證據表明，全食物飲食富含有助于促進健康微生物群的食物，可能有助于預防和減少銀屑病和其他自身免疫性疾病的癥狀。)[37]

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[38]

The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-alpha induces hepatocyte apoptosis and lethal effects are due to secreted TNF-alpha and not to cell-associated TNF-alpha. An exaggerated production of TNF-alpha has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-gamma and IFN-alpha/beta are involved in the macrophage-induced release of TNF-alpha. The prominent role of LPS and TNF-alpha in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-alpha/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-alpha and interleukin (IL)-1beta levels than responders. Moreover, in responders, an equilibrium between IFN-gamma and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th)1 and Th2 derived cytokines could be envisaged in the non-responders.

(LPS會導致肝損傷)

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Compared with the stool samples of healthy controls, several major bacterial species were underrepresented or absent in the gut microbiota of psoriatic arthritis patients. These included Akkermansia, the most common mucolytic bacterium in healthy subjects. Intriguingly, Akkermansia counts are decreased 15-fold in Crohn’s disease and 92-fold in ulcerative colitis, according to the rheumatologist.

Other bacterial species markedly less abundant in the psoriatic arthritis patients’ gut flora were Ruminoccocus, Alistipes, and Roseburia. Like Akkermansia, these are mucin-degrading bacteria that promote a healthy gut environment, and they, too, are reduced in inflammatory bowel disease, Dr. Scher said.(銀屑病關節炎患者腸道菌群中明顯不太豐富的其他細菌種類有瘤胃菌群、阿利斯蒂普斯菌群和Roseburia菌群。Scher博士說，與Akkermansia一樣，這些是粘蛋白降解細菌，可促進腸道健康，在炎癥性腸病中也會減少)[39]

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The food we eat comes into direct contact with our gut microbiota so the macronutrients, vitamins, minerals, fibre, microorganisms and plant bioactive compounds from our diet are incredibly important.?

But of particular note is the role of a cuppa when it comes to sorting our gut microbiota. New research reveals that four to five cups of tea per day could boost ‘friendly’ gut bacteria. The good news is that a range of different teas including black tea, green tea, oolong and pu-erh, can contribute to a positive shift in our gut microbiota. This positive shift can help avoid gut dysbiosis, in which gut bacteria composition becomes detrimental.

And the secret lies in tea’s rich array of polyphenols – natural flavonoid compounds found in the tea plant. Tea is one of the richest sources of flavonoid polyphenols in the diet of many global diets, demonstrating a prebiotic effect and rebalancing our gut microbiota towards more favourable strains including Lactobacillus, Faecalibacteria and Bacteroides.

A 10-day study where participants drank four to five cups of green tea daily instead of water, also showed increased levels of Bifiobacterium, a healthy bacteria strain.

Studies further proved that green and black tea polyphenols increased Bacteriodetes phyla and reduced Firmicutes. Green, oolong, black and pu-erh teas also increased bacterial diversity; important for strengthening immunity – vital for those with psoriasis – and also something particularly relevant in the current global situation.

Tea cup surrounded by tea leaves
Foods to help psoriasis
A change in diet can have an effect in as little as one or two days6 – so it’s worth eating more healthily from today.

High fibre diets have been linked with improved microbiota balance7.
Polyphenols are organic compounds found naturally in plants especially tea, fruits, vegetables, cocoa, wine, soya, spices and nuts. In general8, polyphenol-rich diets boost levels of beneficial bacteria and decrease more harmful species. Tea is one of the main sources of polyphenols in the British diet.
Vitamin A, vitamin D and long-chain omega-3 fatty acids all have roles in gut health.?
Fermented foods and probiotic drinks contain live ‘good’ bacteria. If these are able to survive the pH extremes of the stomach and small intestine, the bacteria travel to the large intestine where they become established. A recent review9 examined evidence from 19 studies to assess the effect of fermented foods on the human gut microbiota. Promising findings were reported, but no overall conclusion.?
Prebiotics are non-digestible carbohydrates, which can change the gut microbiota towards healthier species. They are found in various fruit and vegetables, such as tomatoes, onions, garlic, leeks, asparagus and bananas. Recent evidence suggests that tea can now also be considered a prebiotic. Prebiotics are relatively stable and, unlike probiotics, can be relied on to arrive relatively unchanged in the gut, despite digestive enzymes.?
Avoid ultra-processed foods, which tend to be low in fibre and high in fat. They have been linked with inflammation and gut dysbiosis10.
Treatment options
In addition to taking responsibility for improving our gut microbiota, there is also a wide range of effective treatments for psoriasis. These range from over-the-counter moisturisers and emollients to prescription creams, ointments and medicines.

Finding the most effective therapy is often a matter of trial and error and new products are being introduced all the time, such as medicated tapes with a fixed dose of steroid. It’s important to keep going back to your doctor, or dermatologist, for advice if you are not happy.

At home, try and ensure you eat a balanced diet and make two to three cuppas part of that daily diet to help good gut health.

If you need support with your gut health, use the advanced search to find a nutrition professional who’s right for you.

Dr Tim Bond is a chemist, natural health expert and tea scientist. Dr Tim is part of the Tea Advisory Panel, a novel health group that conducts scientific studies into the healthy role of black tea in diets.
?

重點翻譯如下:

秘密在于茶葉中含有豐富的多酚——茶樹中發現的天然類黃酮化合物。在許多全球飲食中，茶是黃酮類多酚最豐富的來源之一，顯示出益生元效應，并使我們的腸道微生物群向更有利的菌株（包括乳酸桿菌、糞桿菌和類桿菌）重新平衡。

一項為期10天的研究顯示，參與者每天喝四到五杯綠茶，而不是水，雙歧桿菌（一種健康的細菌）的含量也有所增加。

研究進一步證明，綠茶和紅茶多酚增加了細菌門，減少了厚壁菌門。綠茶、烏龍茶、紅茶和普洱茶也增加了細菌多樣性；這對增強免疫力很重要——對銀屑病患者來說至關重要——也是當前全球形勢下特別相關的事情。

被茶葉包圍的茶杯

幫助牛皮癬的食物

飲食的改變只需一兩天就能產生效果6，因此從今天開始，更健康的飲食是值得的。

高纖維飲食與改善微生物群平衡有關7。

多酚是天然存在于植物中的有機化合物，尤其是茶、水果、蔬菜、可可、葡萄酒、大豆、香料和堅果。一般來說，富含多酚的飲食可以提高有益細菌的水平，減少更多有害物種。茶是英國飲食中多酚的主要來源之一。

維生素A、維生素D和長鏈ω-3脂肪酸都對腸道健康有作用[40]

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隨著銀屑病的改善，瘤胃球菌科、黃連球菌屬和布勞提亞屬的豐度顯著降低，銀屑病患者的豐度顯著增加[41]?

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Psoriasis and the Microbiome
Studies have shown that individuals with psoriasis often have an unbalanced gut microbiome and fewer bacterial species. People with psoriasis display low levels of helpful bacteria such as Lactobacillus and Bifidobacterium, and increased levels of harmful species including E. coli and Salmonella. The gut dysbiosis in people with psoriasis could lead to more inflammation and activation of immune cells. All of these changes could ultimately affect the level of inflammation in the body.

Although scientists do not know if leaky gut syndrome occurs regularly during psoriasis, some evidence suggests a connection. Additional studies are required to confirm the presence of leaky gut syndrome during psoriasis. However, the evidence suggests that treatment options targeting the microbiome could be beneficial for some people living with psoriasis.

Probiotics for Psoriasis
Probiotics are beneficial live bacteria that support the microbiome — in other words, good bacteria. When people talk about using probiotics to treat psoriasis or another health condition, they are generally referring to foods or supplements containing these good bacteria. Foods containing probiotics include:(

研究表明，銀屑病患者的腸道微生物組不平衡，細菌種類較少。銀屑病患者的有益細菌（如乳酸桿菌和雙歧桿菌）水平較低，有害物種（包括大腸桿菌和沙門氏菌）水平較高。銀屑病患者的腸道生態失調可能導致更多的炎癥和免疫細胞的激活。所有這些變化最終都會影響體內的炎癥水平。

雖然科學家不知道銀屑病期間是否經常發生腸漏綜合征，但一些證據表明兩者之間存在聯系。需要更多的研究來證實銀屑病期間是否存在腸漏綜合征。然而，證據表明，針對微生物組的治療方案可能對一些銀屑病患者有益。

銀屑病益生菌

益生菌是有益的活細菌，支持微生物群，換句話說，是好細菌。當人們談論使用益生菌治療牛皮癬或其他健康狀況時，他們通常指的是含有這些有益細菌的食品或補充劑。含有益生菌的食品包括：

（酸奶、凱菲爾、坦佩、康普茶、酸菜)

In a separate study, people with severe pustular psoriasis were treated with the probiotic supplement Lactobacillus sporogenes(芽孢乳酸桿菌)?three times daily. Many of the study participants showed significant improvement within two weeks of treatment, and some even achieved remission after four weeks.[42]

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These include Akkermansia muciniphila, which helps regulate glucose metabolism and immune activity, and Faecalibacterium prausnitzii, which is a main producer of butyrate, an anti-inflammatory short-chain fatty acid that is important in colon health.(生產丁酸鹽的Faecalibacterium prausnitzii)

Certain bacterial species in the gut microbiome of humans have been shown to significantly influence our immune systems. For instance, bacterial species such as Akkermansia muciniphila and Faecalibacterium prausnitzii favor the growth of regulatory T cells, a cell type that has anti-inflammatory properties and protects against autoimmunity. In theory, a relative decline in these bacterial species within the gut could lead to a loss of their anti-inflammatory effects, acting as an environmental trigger for the development of inflammatory diseases, such as psoriasis, in certain individuals.

翻譯

人類腸道微生物群中的某些細菌種類已被證明會顯著影響我們的免疫系統。例如，粘液阿克曼菌（Akkermansia muciniphila）和prausnitzii糞桿菌（Faecalibacterium prausnitzii）等細菌有利于調節性T細胞的生長，調節性T細胞是一種具有抗炎特性和防止自身免疫的細胞類型。

Liao: Clinical trials have been done investigating the use of probiotic supplementation in treating psoriasis. In a double-blind, placebo-controlled, clinical trial, researchers found no significant improvement in psoriasis symptoms in patients administered a probiotic containing Lactobacillus. In another study, however, when used as an adjuvant to topical treatment, probiotic supplementation significantly improved psoriasis severity in patients. Probiotic supplementation with Bifidobacteria infantis has also been shown to decrease systemic concentrations of pro-inflammatory TNF-alpha and C-reactive protein in psoriasis patients. The evidence for the effect of antibiotics is mixed, with some studies showing a beneficial effect on psoriasis and others showing a worsening effect.(乳酸桿菌無效、雙歧桿菌有效)

For instance, research suggests that the gut microbiome is further altered in psoriatic arthritis versus skin-only psoriasis patients, with more significant reductions in Akkermansia, Ruminococcus and Pseudobutyrivibrio species seen.（Akkermansia、瘤胃球菌和假丁酸菌物種顯著減少）

上面內容來自【44】

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So how does that apply to psoriasis? Well, let me tell you about two patients.

I’ll never forget a four-year-old girl who once arrived in my office with psoriasis from head to toe. She had been suffering since the age of six months. She looked like a red, swollen, inflamed mess.

This poor girl was on immune-suppressing drugs to address her numerous symptoms and ended up in the hospital from a MRSA (staph) infection. Doctors had kept her on antibiotics for a month.

While in my office, this little girl had to use the bathroom. You can imagine my horror when I heard her scream when she urinated because her genitals were inflamed with psoriasis, as well. ?Just when I thought her suffering couldn’t be any worse…my heart broke for her.

Rather than utilize invasive, potentially harmful creams and other drugs (which clearly weren’t working anyway), I applied the Functional Medicine approach with this girl. I looked at her brief but exhaustive health history. She was born by C-section. She had leaky gut and abnormal gut flora because of a long history of taking antibiotics and steroids that created a yeast overgrowth.

My solution was simple but powerfully effective: Remove the bad and add the good.

We eliminated trigger foods like gluten. We cleaned up the bad yeast with an antifungal. We incorporated anti-inflammatories, healthy fats and supplements like probiotics, vitamin D, vitamin A and zinc to heal her skin. I trusted she would get better even though she was the worst case I had ever seen.

Two weeks later, this little girl’s father called. “Dr. Hyman,” he said, “my daughter’s skin has completely cleared.” ?My broken heart healed a little bit that day.

Now, let’s look at a patient on the other end of the spectrum. ?I took this same approach with a 56-year-old doctor who came to see me with psoriatic arthritis. Despite loving his work, he was about to quit his job as a surgeon in a Massachusetts hospital because he was tired, overweight and could no longer operate due to the joint pain . I told him we needed to fix his gut with an elimination diet, get rid of the parasites, and introduce the right nutrients.

Six weeks later, my patient was off his immune suppressive drugs and a long list of other drugs. He had no symptoms. His digestive symptoms went away, his skin cleared up, he lost weight, and he could return to work.?

While tempting to label these two patients’ transformations as miracles, they weren’t. Rather, they highlighted the power of Functional Medicine.

Heal Psoriasis with these Strategies

While psoriasis often becomes linked with gluten intolerances, that isn’t always the case. The three biggest culprits are:

Gluten sensitivities
Yeast overgrowth in the gut
Heavy metals exposure
To address psoriasis, I remove these obstacles while restoring the body’s natural balance. It really becomes that simple. Take away the things that cause the problem and add those that ameliorate it.

With that approach, I’ve found these eight strategies can naturally heal psoriasis without steroids, creams and other invasive procedures.

Eat a whole food, anti-inflammatory diet. Focus on anti-inflammatory foods including wild fish and other sources of omega-3 fats, red and purple berries (rich in polyphenols), dark green leafy vegetables, orange sweet potatoes and nuts. Add anti-inflammatory herbs, including turmeric (a source of anti-inflammatory curcumin), ginger and rosemary to your daily diet. Eliminate inflammatory foods such as refined, omega-6 and inflammatory oils – including: ?corn, soy and safflower oils.
Remove food sensitivities. These include gluten and dairy.?
Test for heavy metal toxicity. Mercury and other metals trigger or exacerbate psoriasis.?
Fix your gut. Your gut plays a significant role in skin health. One study found intestinal permeability (or leaky gut) can contribute to psoriasis. Yeast overgrowth, abnormal gut flora and other gut issues can also trigger or exacerbate psoriasis. If you suspect these or other issues, work with an integrative practitioner to optimize your gut health. I often use prescription or herbal antifungals to treat the yeast.
Use the right supplements. Nutrients like fish oil, vitamin D and probiotics can help eliminate psoriasis. Also consider anti-inflammatory nutrients like quercetin, grape seed extract and rutin. Using UltraInflamX PLUS 360 as a meal replacement also helps many of my patients with inflammation. You can find these and other professional-grade supplements in my online store.(

那么這對牛皮癬有什么影響呢？好吧，讓我告訴你兩個病人的情況。

我永遠不會忘記一個四歲的小女孩，她曾經來過我的辦公室，從頭到腳都得了牛皮癬。她從六個月大起就一直在受苦。她看起來像一團紅腫發炎的爛攤子。

這個可憐的女孩當時正在服用免疫抑制藥物來緩解她眾多的癥狀，最后由于感染了葡萄球菌而住進了醫院。醫生讓她連續服用抗生素一個月。

在我的辦公室里，這個小女孩不得不上廁所。你可以想象當我聽到她小便時的尖叫時我的恐懼，因為她的生殖器也患了牛皮癬。就在我認為她的痛苦不會更糟的時候……我為她心碎了。

我沒有使用侵入性的、潛在有害的藥膏和其他藥物（顯然無論如何都不起作用），而是對這個女孩采用了功能醫學的方法。我看了她簡短但詳盡的健康史。她是剖腹產出生的。由于長期服用抗生素和類固醇導致酵母菌過度生長，她有腸道滲漏和腸道菌群異常。

我的解決方案很簡單，但非常有效：去掉壞的，添加好的。

我們消除了谷蛋白等易引發過敏的食物。我們用抗真菌劑清除了壞酵母。我們加入了消炎藥、健康脂肪和益生菌、維生素D、維生素A和鋅等補充劑來治療她的皮膚。我相信她會好起來的，盡管她是我見過的最糟糕的情況。

兩周后，這個小女孩的父親打電話來。“海曼醫生，”他說，“我女兒的皮膚已經完全干凈了。”那天我破碎的心愈合了一點。

現在，讓我們看看另一端的患者。我對一位56歲的醫生采取了同樣的方法，他來看望我患有銀屑病性關節炎。盡管熱愛自己的工作，但他即將辭去馬薩諸塞州一家醫院外科醫生的工作，因為他感到疲勞、超重，并且由于關節疼痛無法再進行手術。我告訴他，我們需要用消除性飲食來修復他的腸道，清除寄生蟲，并引入正確的營養素。

六周后，我的病人停止服用免疫抑制藥物和一長串其他藥物。他沒有任何癥狀。他的消化癥狀消失了，皮膚變干凈了，體重減輕了，他可以重返工作崗位。

雖然很容易將這兩名患者的轉變稱為奇跡，但事實并非如此。相反，他們強調了功能醫學的力量。

用這些方法治療銀屑病

雖然銀屑病通常與麩質不耐受有關，但情況并非總是如此。三大罪魁禍首是：

面筋敏感性

腸道內酵母過度生長

重金屬暴露

為了解決牛皮癬，我在恢復身體自然平衡的同時消除了這些障礙。事情就這么簡單了。去掉引起問題的東西，加上改善問題的東西。

通過這種方法，我發現這八種策略可以自然治愈牛皮癬，而無需類固醇、面霜和其他侵入性治療。

吃全食，消炎飲食。關注抗炎食品，包括野生魚類和其他來源的歐米茄-3脂肪、紅色和紫色漿果（富含多酚）、深綠色葉菜、橙色甘薯和堅果。在日常飲食中添加抗炎草藥，包括姜黃（一種抗炎姜黃素的來源）、生姜和迷迭香。消除發炎性食物，如精制、歐米茄-6和發炎性油脂，包括：玉米油、大豆油和紅花油。

消除食物過敏。這些包括麩質和奶制品。

重金屬毒性試驗。汞和其他金屬會引發或加劇牛皮癬。

治好你的肚子。你的腸道對皮膚健康起著重要作用。一項研究發現，腸道通透性（或腸道滲漏）可能導致牛皮癬。酵母過度生長、腸道菌群異常和其他腸道問題也會引發或加重銀屑病。如果您懷疑這些或其他問題，請與綜合從業者合作，優化您的腸道健康。我經常使用處方藥或草藥抗真菌藥來治療酵母菌。

使用正確的補充劑。魚油、維生素D和益生菌等營養素有助于消除銀屑病。還可以考慮抗炎素如槲皮素、葡萄籽提取物和蘆丁。使用UltraInflamX PLUS 360作為膳食替代品也有助于我的許多炎癥患者。你可以在我的網上商店找到這些和其他專業級的補充劑。

)

Exercise regularly. Regular exercise is a natural anti-inflammatory. One study found increased physical exercise along with dietary intervention reduced psoriasis severity in systemically treated overweight or obese patients with active psoriasis. You don’t have to go to the gym, run on a treadmill and pump iron to stay in shape. Just start moving around more. Go for walks with your friends or family. Go out and do some gardening. Play Frisbee in the park with your kids. Pick up a tennis racket and just knock a tennis ball around. Anything you can do to get out and move your body can be considered exercise. So don’t think that you absolutely have to go to the gym to get fit. Just use your body more.
Practice deep relaxation. Studies show chronic stress can influence the development and exacerbation of psoriasis. The proportion of psoriasis patients who believe stress affects their skin condition ranges from 37 to 78 percent, and researchers believe stress may worsen psoriasis severity and may even lengthen the time to disease clearance. Calming techniques such as yoga, deep breathing, biofeedback, massage or my UltraCalm CD can reduce stress and anxiety to promote relaxation.
Sleep for 8 hours every night. Studies show patients with psoriasis suffer from more sleep disturbances. While some situations require professional help, you can improve sleep quality and quantity by implementing my 19 sleep tips from this blog.
If you’re looking for a place to get started to eliminate psoriasis, start with food. ?Try The Blood Sugar Solution 10-Day Detox Diet, which is anti-inflammatory and removes gluten, dairy and other food sensitivities. I’ve had patients create amazing, lasting changes to skin conditions and other problems in just 10 days. With this approach you can heal from the inside out with nutrients, not drugs.

While you might also consider working with a Functional Medicine practitioner to address issues like mercury or yeast overload, The Blood Sugar Solution 10-Day Detox Diet makes an excellent way to start.(

經常鍛煉。經常運動是一種天然的消炎藥。一項研究發現，在接受系統治療的超重或肥胖活動性銀屑病患者中，增加體育鍛煉和飲食干預可降低銀屑病的嚴重程度。你不必去健身房，在跑步機上跑步，也不必用力熨斗來保持身材。開始多走動。和你的朋友或家人一起散步。出去做些園藝工作。和孩子們在公園里玩飛盤。拿起一個網球拍，把一個網球打過來就行了。你能做的任何運動都可以被認為是鍛煉。所以不要認為你一定要去健身房健身。多用你的身體。

練習深度放松。研究表明慢性壓力會影響銀屑病的發展和惡化。認為壓力會影響皮膚狀況的銀屑病患者比例在37%到78%之間，研究人員認為壓力可能會加重銀屑病的嚴重程度，甚至可能延長疾病清除的時間。瑜伽、深呼吸、生物反饋、按摩或我的超平靜CD等鎮靜技術可以減輕壓力和焦慮，促進放松。

每晚睡8小時。研究表明，銀屑病患者睡眠障礙較多。雖然有些情況需要專業幫助，但你可以通過實施我在本博客中的19個睡眠技巧來提高睡眠質量和數量。

如果你正在尋找一個地方開始消除牛皮癬，從食物開始。嘗試血糖溶液10天排毒飲食，這是消炎和消除面筋，乳制品和其他食物的敏感性。我曾讓患者在短短10天內對皮膚狀況和其他問題產生驚人、持久的變化。通過這種方法，你可以用營養而不是藥物從內而外治愈。

同時你也可以考慮和一個功能性的醫生一起解決像汞或酵母超載這樣的問題，血糖溶液10天排毒飲食是一個很好的開始方法。)

上面內容來自【45】

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What are short-chain fatty acids?
One important function of microbes in the gut flora is the production of short-chain fatty acids via the break-down of complex carbohydrates in food [2,3]. Examples of short-chain fatty acids are propionate, acetate, and butyrate.（什么是短鏈脂肪酸？

腸道菌群中微生物的一個重要功能是通過分解食物中的復雜碳水化合物產生短鏈脂肪酸[2,3]。短鏈脂肪酸的例子有丙酸鹽、乙酸鹽和丁酸鹽。）

Short-chain fatty acids are thought to:

Help maintain the balance in the gut between its inflammatory and regulatory functions [2]（短鏈脂肪酸被認為是：

幫助維持腸道炎癥和調節功能之間的平衡[2]）

Anti-inflammatory effects
Certain microbes promote white blood cells which contribute to anti-inflammatory responses [8]
Short-chain fatty acids inhibit inflammation and regulate immune cells [3]
Increased intestinal permeability
Changes in gut flora may increase the permeability of the intestine with subsequent leakage of gut microbiota into the bloodstream and skin resulting in systemic or cutaneous inflammation [2,3]
Neurotransmitters
Gut organisms alter levels of neurotransmitters which may influence the skin [2].
The gut microbiome and atopic dermatitis
Some studies have observed that gut dysbiosis (microbial imbalance) precedes the onset of atopic dermatitis [3,11,12]. Although the relationship is not clear, there are distinct differences in the gut microbiome between people with and without atopic dermatitis.

Infants who go on to develop atopic dermatitis have been reported to have:

Lower colonic microbial diversity [12]
Altered gut levels of certain gut bacteria (Staphylococcus aureus, Bacteriodetes and Clostridia [2,11])
Lower levels of Bifidobacterium levels, which are inversely correlated with severity [7]
Lower levels of Bacteroides and certain mucin-producing bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae) [7,11].
The gut microbiome and acne
Observed changes in microbial composition between individuals with and without acne may be due to:

Interactions with the mammalian target of rapamycin (mTOR) pathway and its effects on the intestinal barrier and metabolic function [3]
Dysbiosis stimulated by psychological stress and diet resulting in systemic inflammation [3].
Other
Small studies have reported possible associations of alterations in the gut microbiome with rosacea, psoriasis, and wound healing [3,5,9].

What are probiotics, prebiotics, and synbiotics?
Probiotics are defined by the World Health Organisation (WHO) as “live microorganisms which when administered in adequate amounts, confer a health benefit on the host” [5,10]. The most commonly used bacteria in probiotics are Lactobacilli and Bifidobacteria [2,5].

Prebiotics are non-digestible fibres that stimulate certain beneficial bacteria in the gut. The most common of these are non-digestible oligosaccharides [2].

Synbiotics are a combination of probiotics and prebiotics [2].

What is the role of probiotics, prebiotics, and synbiotics in skin disease?
The main role of probiotics and prebiotics is to restore and encourage the production of beneficial microorganisms in the gut [2]. Research is focusing on their therapeutic potential and results to date have been conflicting [9].

The role of probiotic supplements in the prevention of atopic dermatitis is being investigated in pregnancy and infancy to determine if they can improve or help prevent skin disease [2,11]. Probiotics have not been shown to treat established dermatitis [5,12].

It has been reported that probiotics may lead to an improvement in acne by reducing inflammation and decreasing ceramide production [12].

（抗炎作用

某些微生物促進白細胞，從而促進抗炎反應[8]

短鏈脂肪酸抑制炎癥并調節免疫細胞[3]

腸通透性增加

腸道菌群的變化可能增加腸道的通透性，隨后腸道微生物群泄漏到血液和皮膚中，導致全身或皮膚炎癥[2,3]

神經遞質

腸道生物改變可能影響皮膚的神經遞質水平[2]。

腸道菌群與特應性皮炎

一些研究發現，腸道生態失調（微生物失衡）先于特應性皮炎[3,11,12]。雖然這種關系尚不清楚，但患有和未患有特應性皮炎的人的腸道微生物組有明顯的差異。

據報道，繼續發展為特應性皮炎的嬰兒有：

結腸微生物多樣性較低[12]

某些腸道細菌（金黃色葡萄球菌、桿菌和梭菌[2,11]的腸道水平改變）

雙歧桿菌水平較低，與嚴重程度呈負相關[7]

類桿菌和某些粘蛋白產生菌的水平較低（粘蛋白Akkermansia muciniphila、gnavus瘤胃球菌和Lachnospiraceae）[7,11]。

腸道微生物群與痤瘡

有痤瘡和無痤瘡的個體之間觀察到的微生物成分變化可能是由于：

與雷帕霉素（mTOR）途徑哺乳動物靶點的相互作用及其對腸道屏障和代謝功能的影響[3]

心理壓力和飲食刺激的失調，導致全身炎癥[3]。

另外

小型研究報告了腸道微生物組的改變可能與酒渣鼻、牛皮癬和傷口愈合有關[3,5,9]。

什么是益生菌、益生元和合生元？

世界衛生組織（WHO）將益生菌定義為“活微生物，當給予足夠數量的益生菌時，會給宿主帶來健康益處”[5,10]。益生菌中最常用的細菌是乳酸桿菌和雙歧桿菌[2,5]。

益生元是刺激腸道中某些有益細菌的不易消化纖維。其中最常見的是不易消化的低聚糖[2]。

合生元是益生菌和益生元的組合[2]。

益生菌、益生元和合生元在皮膚病中的作用是什么？

益生菌和益生元的主要作用是恢復和鼓勵腸道中有益微生物的產生[2]。研究的重點是它們的治療潛力，迄今為止的結果一直相互矛盾[9]。

益生菌補充劑在預防特應性皮炎中的作用正在妊娠期和嬰兒期進行調查，以確定它們是否可以改善或幫助預防皮膚病[2,11]。益生菌尚未被證明能治療已確定的皮炎[5,12]。

據報道，益生菌可以通過減少炎癥和神經酰胺的產生來改善痤瘡[12]。）

上面內容來自【47】

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希波克拉底講過："All disease starts in the gut.”"

?
Lessons from bypass surgery patients?
In 1975, Dr. Ely himself discovered the “bypass surgery syndrome” (which later was renamed bowel-associated dermatosis-arthritis syndrome). ?Patients presented with papulopustules, arthralgia and hypersensitivity to bacteria (especially Streptococcus pyogenes, the same bug that causes strep throat)– all after a bypass surgery. ?Almost all these patients had antibodies to peptidoglycan (PG: well-conserved and essential component of the bacterial cell wall). ?Interestingly, his psoriasis patients also had high titers of PG antibodies!3 ? This became the basis of his hypothesis that psoriasis may have a similar mechanism that involved the gut. ??

旁路手術患者的經驗教訓

1975年，伊利博士自己發現了“旁路手術綜合征”（后來更名為腸道相關皮膚病關節炎綜合征）。患者出現丘疹膿皰、關節痛和對細菌過敏（尤其是化膿性鏈球菌，導致鏈球菌性咽喉炎的同一種細菌）——所有這些都是在搭橋手術后出現的。幾乎所有這些患者都有肽聚糖抗體（PG：細菌細胞壁的高度保守和基本成分）。有趣的是，他的銀屑病患者也有高滴度的PG抗體！這成為了他的假設的基礎，即銀屑病可能有一個類似的機制，涉及腸道。

Gut-skin relationship in psoriasis ?
It was later discovered that psoriatic skin lesions were also loaded with PGs and PG-specific Th1 cells4. ?PGs are shown to have similar effects in vivo as endotoxin. ?So, it makes sense that acute psoriasis and endotoxemia have similar symptoms: fevers, leukocytosis, increased capillary permeability, elevated liver enzymes, and decreased complement levels. ?Moreover, gut bacterial DNA and other bacterial markers are present in psoriatic blood at higher levels, suggesting a “leaky gut” in psoriasis. ?Fascinating! ??

Now, figure 1 below shows a picture from Dr. Ely’s first talk on this topic in 1981. ?In psoriasis, PGs are absorbed from the gut into the 1) portal circulation, causing liver damage and 2) systemic circulation and end up in the skin and joints– leading to psoriasis and psoriatic arthritis, respectively. ?Dr. Ely calls psoriasis a “cathartic” event, whereby the body increases skin turnover in order to shed the PGs that is responsible for the systemic inflammation. Whoa, what a concept! It makes sense, though, doesn’t it? ?So, how does Dr. Ely suggest we treat this disease? ?

Skin Gut Axis in Psoriasis
Figure 1: In psoriasis, peptidoglycans are absorbed from the gut into the 1) portal circulation, causing liver damage and 2) systemic circulation and end up in the skin and joints– leading to psoriasis and psoriatic arthritis, respectively.
Bile acid therapy?
Psoriasis patients have bad liver and abnormal bile. ?They also have a significant reduction of bile acid in bile5. ?Why does this matter? Well, bile acids have the ability to split endotoxins into non-toxic fragments, and they are also bactericidal. ?So, what if you replete bile acids in psoriasis? ?In one study of 500 psoriasis patients who were treated with bile acid (dehydrocholic acid) for 1-8 weeks, 434 (78.8%) became asymptomatic, compared to only 24.9% who received only conventional therapy6. ?Bile acid treatment of acute psoriasis led to 95.1% complete recovery. ?In another study, treatment of liver disease with bile acids led to dramatic improvement in those who also had psoriasis7.

The magic protocol?
Here you go. ?Dr. Ely says that brands don’t matter and most of these are very affordable. ?I looked it up, and each of the following should cost about $10 –20 per month.

For 4 months: Azithromycin 500mg for 4 days, with 10 days between doses. ?This treats pyogenes, which is elevated in psoriatic small intestines
Probiotics containing Saccromycesboulardii 500mg 3 times daily (consider probiotics when prescribing any antibiotic for that matter)
Bile acids with each meal (ex: Ox bile, Duozymes– anything is fine)
Bioflavanoids: Quercetin 500mg twice daily
Now, it’s important to discuss and encourage a low-fat diet that is high in high-fiber (vegetables and fruits) and low in meats. ?It’s imperative that patients avoid alcohol and any peppers while on bile acid therapy, which can interfere with its efficacy.

Here are before and after photographs after just one month after this therapy. ?I know, it’s remarkable! ?Oh, and p.s., Dr. Ely recommends oral vitamin D in psoriasis patients — 5000IU vitamin D a day.

Before and after bile acid therapy

Before and after acid bile therapy 2

Concluding thoughts

I’m not saying let’s ditch the pharmaceuticals. ?But when I have mentioned this therapy with my psoriasis patients (albeit a short list so far), every single one of them was so grateful and excited to try a modality that is holistic, easily accessible, and affordable. ?And your staff is happier because no prior authorizations are needed! ?Hippocrates implored healers to “Let food be thy medicine and medicine be thy food.” ?We don’t have to take out the prescription pad right away, every time. ?When as physicians we take a more integrative stance, we give our patients more options and empower them to make lifestyle changes that will bring healing from the inside out. ? Let’s do it!!

Haines Ely M.D. is a clinical professor of dermatology at U.C. Davis and spends his days with UC Davis residents at Mather Field VA Hospital in Sacramento. He discovered the bowel bypass syndrome in 1975, which began a lifelong study of the interconnection of the bowel and the skin. ?He has successfully treated hundreds of psoriasis patients with bile acids and citrus bioflavinoids, plu.

（

銀屑病的腸皮膚關系

后來發現銀屑病皮損也含有PGs和PG特異性Th1細胞4。PGs在體內的作用與內毒素相似。因此，急性銀屑病和內毒素血癥有相似的癥狀是有道理的：發燒、白細胞增多、毛細血管通透性增加、肝酶升高和補體水平降低。此外，銀屑病患者血液中存在較高水平的腸道細菌DNA和其他細菌標記物，提示銀屑病患者存在“腸道滲漏”。極有吸引力的

下面的圖1顯示了Ely博士1981年關于這個話題的第一次演講的圖片。在銀屑病中，PG從腸道吸收進入1）門靜脈循環，導致肝臟損傷和2）體循環，最終進入皮膚和關節——分別導致銀屑病和銀屑病性關節炎。伊利博士將銀屑病稱為“瀉藥”事件，身體通過增加皮膚更新來釋放導致全身炎癥的PGs。哇，多好的概念啊！不過這是有道理的，不是嗎？那么，伊利博士建議我們如何治療這種疾病呢？

銀屑病的皮膚-腸道軸

圖1：在銀屑病中，肽聚糖從腸道被吸收進入1）門脈循環，導致肝損傷和2）體循環，最終進入皮膚和關節——分別導致銀屑病和銀屑病關節炎。

膽汁酸療法

銀屑病患者肝臟不好，膽汁異常。它們還能顯著減少膽汁中的膽汁酸5。為什么這很重要？膽汁酸有能力將內毒素分解成無毒的片段，它們也有殺菌作用。那么，如果銀屑病患者體內充滿膽汁酸怎么辦？在一項研究中，500名銀屑病患者接受了膽汁酸（脫氫膽酸）治療1-8周，其中434名（78.8%）患者無癥狀，而僅接受常規治療的患者只有24.9%。膽汁酸治療急性銀屑病的痊愈率為95.1%。在另一項研究中，用膽汁酸治療肝病可使患有銀屑病的患者得到顯著改善7。

魔法協議

干得好。伊利博士說，品牌并不重要，而且大多數品牌都非常實惠。我查了一下，下面的每一項每月大概要花10-20美元。

4個月：阿奇霉素500mg，連續4天，兩次給藥間隔10天。這是治療化膿，這是提高在銀屑病小腸

含有Saccromycesboulardii的益生菌，每日3次，每次500mg（在為此開抗生素處方時，請考慮益生菌）

每頓飯都含有膽汁酸（例如：牛膽汁、多菌酶——任何東西都可以）

生物類黃酮：槲皮素500mg，每日兩次

現在，重要的是討論和鼓勵高纖維（蔬菜和水果）和低肉類的低脂飲食。在接受膽汁酸治療時，患者必須避免飲酒和任何辣椒，這可能會影響其療效。

這是治療一個月后的前后照片。我知道，這太了不起了！另外，伊利博士建議銀屑病患者口服維生素D——每天5000 IU維生素D。

膽汁酸治療前后

酸性膽汁治療前后2

結語

我不是說我們放棄藥物。但當我在我的銀屑病患者中提到這種治療方法時（盡管目前只是一個簡短的列表），他們中的每一個人都非常感激和興奮地嘗試了一種全面、容易獲得和負擔得起的治療方法。您的員工更快樂，因為不需要事先授權！希波克拉底懇求治療師“讓食物成為你的藥，讓藥物成為你的食物。”我們不必每次都馬上拿出處方紙。當我們作為醫生采取更為綜合的立場時，我們會給患者更多的選擇，讓他們能夠改變生活方式，從內到外帶來治愈。讓我們做吧！！

海恩斯·伊利醫學博士是加州大學戴維斯分校的皮膚病臨床教授，在薩克拉門托的馬瑟菲爾德弗吉尼亞醫院與加州大學戴維斯分校的居民共度時光。1975年，他發現了腸旁路綜合征，從此開始了對腸道和皮膚相互聯系的終身研究。他已經用膽汁酸和柑橘類生物類黃酮成功治療了數百名銀屑病患者。

）

上述內容來自【48】

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Reference:

【1】科研 | STTT: 生酮飲食改變菌群降低結腸3型淋巴細胞，緩解小鼠結腸炎|微生物群|結腸炎|菌群|飲食|科研|腸道|炎癥|-健康界

【2】JCI：FODMAP飲食促進腸道炎癥的機制是什么 | 熱心腸日報

【3】腸道“壞菌”產物——脂多糖（LPS）的作用機制與干預方案

【4】14 Factors that May Reduce Lipopolysaccharides (LPS) - SelfHacked

【5】Eliminating Lipopolysaccharide (LPS) Using Lactic Acid Bacteria (LAB) and a Fraction of its LPS-Elimination Protein - PubMed

?【6】Regulation of Gut Microbiota and Metabolic Endotoxemia with Dietary Factors | HTML

【7】炎癥性腸病與腸道菌群|免疫系統|腸道細菌_網易訂閱

【8】高脂飲食，會傷害腸道嗎?生酮飲食和腸道的關系 - 知乎

【9】人體腸道的長度總長多少_有問必答_快速問醫生

【10】內毒素和外毒素之間的差異 | 分博士

【11】]細菌外毒素與內毒素的主要區別是什么？

【12】名家專欄 ｜ 日常生活中，滅活乳酸菌可減除食品中黃曲霉毒素

【13】The connection between psoriasis and the gut

【14】Skin-gut axis: SkinBioTherapeutics and Winclove partner on probiotics to treat psoriasis

【15】Gut Health and Skin: Exploring the Connection - Chris Kresser

【16】The Science Behind Leaky Gut, the Gut Microbiome, and Arthritis

【17】Psoriasis, more than a skin disease? The involvement of gut microbes – Atlas of Science?
【18】New Research Says These Are the Foods You Should Avoid If You Have Psoriasis (and What You Should Eat Instead!)

【19】What Is The Connection Between Leaky Gut And Psoriasis?

【20】Microsoft Academic

【21】Psoriasis and Microbiota: A Systematic Review
【22】People with Psoriasis More Likely to Develop Certain Gut Disorders | Live Science

【23】Clinical Implications of Intestinal Barrier Damage in Psoriasis | JIR

【24】Pardon Our Interruption

【25】A Gut Microbiota Approach to Psoriasis

【26】Types of psoriasis and how your gut health could be the underlying cause

【27】African Journal of Microbiology Research - gut bacterial microbiota in psoriasis: a case control study

?【28】How To Ease Your Skin Issue By Starting With Your Gut, From An MD

【29】Heal Your Gut, Heal Your Skin

【30】African Journal of Microbiology Research - gut bacterial microbiota in psoriasis: a case control study

【31】Foods High in Sugar and Fat Disrupt the Gut Microbiome and Trigger Psoriasis Flares - Practical Dermatology

【32】IMPACT OF PROBIOTICS ON GUT & SKIN MICROBIOME IN PSORIASIS

【33】[33The Surprising Connection Between Bacteria And Psoriatic Arthritis

【34】Gut microbiota and nutrient interactions with skin in psoriasis: A comprehensive review of animal and human studies

【35】Skin-Gut Axis in Psoriasis Setting and Plan for Action: The Effect of Probiotics Supplementation On Clinical Outcomes, Metabolic Endotoxemia, Inflammation, and Cardiovascular Risk in Patients with Psoriasis | Research Square

【36】Probiotics and Psoriatic Arthritis | Everyday Health

【37】Does Imbalanced Gut Bacteria Influence Psoriasis?

【38】The role of the liver in the response to LPS: experimental and clinical findings - PubMed

【39】Gut-joint connection promising in psoriatic arthritis

【40】Is my psoriasis caused by the gut? - Nutritionist Resource

【41】Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris | medRxiv

【42】Probiotics for Psoriasis: Gut Bacteria and Your Microbiome | MyPsoriasisTeam

【43】Title: Elucidating role of bacteria in psoriatic disease: from skin and gut perspectives.

【44】AAD Reading Room | Wilson Liao, MD, on the Role of the Gut Microbiome in Psoriasis and Psoriatic Arthritis | MedPage Today

【45】8 Strategies to Eliminate Psoriasis | Dr. Mark Hyman

【46】Probiotics can treat psoriasis, shows new clinical data from ADM（做廣告，沒啥用）

【47】The gut microbiome in skin disease | DermNet NZ

【48】

Healing the Gut to Treat Psoriasis? - Next Steps in Dermatology

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