樹突狀細胞	T細胞
腫瘤壞死因子-α（TNF-α）	√
白細胞介素-6(IL-6)	√
白細胞介素-12(IL-12)
白細胞介素-17(IL-17)		√
白細胞介素-20(IL-20)	√
白細胞介素-21(IL-21)		√
白細胞介素-22(IL-22)		√
白細胞介素-23(IL-23)	√
γ干擾素（IFN-γ）		√
IL-1β

Psoriasis is a chronic immune-mediated?inflammatory disease that occurs in 2-4% of
people worldwide affecting skin and in 30% of?cases joints (psoriatic arthritis)

Among these cytokines, IL-22, TNF-α,?and IFN-γ are regarded as the major players in?
psoriatic inflammation.

?Furthermore, they are?
the key molecules in the most commonly?
reported immune mechanism associated with?
psoriasis, namely IL-23/IL-17 axis [20,21]. IL-17,?
which is produced by Th17 cells, was?
numerously found to be upregulated in both?
psoriatic lesions and bloodstream of patients
with psoriasis and psoriatic arthritis [22-29].(IL-23/IL-17在銀屑病患者血液中顯著上升，IL17是淋巴細胞T17產生的)

SCFAs(acetate, butyrate, propionate)

The findings of Chen et al., 2017 [57] revealed?
that mice given L.pentosus GMNL-77 had?
significantly less psoriasis-like skin lesions and?
decreased hyperproliferation of keratinocytes
compared with the imiquimod only treated?
group. The probiotic-treated mice had reduced?
expre（喂食戊糖乳桿菌能明顯降低皮損）

上述內容來自【1】

Th17 cells, as well as Th1 cells and keratinocytes, secrete TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-17A, IL-22, IL-23 participating in pathophysiologic processes of psoriasis [5] and current biological therapies as T cell-directed agents have demonstrated excellent efficacy in psoriasis.?

Among them, serum IL-6 and IL-22 levels were considered to be positively correlated with the severity of psoriasis inpatients [6, 7].

（Th17細胞以及Th1細胞和角質形成細胞分泌TNF-α、IFN-γ、IL-1β、IL-6、IL-12、IL-17A、IL-22、IL-23，參與銀屑病的病理生理過程[5]，目前作為T細胞導向劑的生物療法在銀屑病中已顯示出優(yōu)異的療效。其中，血清IL-6和IL-22水平被認為與銀屑病住院患者的嚴重程度呈正相關[6,7]）

Intestinal permeability was more frequently was reported in plaque psoriasis patients, and the bacterial DNA from the gut can be detected in patients’ blood [13]（斑塊型銀屑病患者的腸道通透性更為常見，并且可以在患者血液中檢測到腸道細菌DNA）

上述內容來自【11】

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菌群	作用	菌群比例-銀屑病患者	菌群比例-正常對照組	睡眠障礙	Secukinumab (生物制劑)
擬桿菌門	抵抗炎癥	9.2%	22%	下降	下降
放線桿菌	抵抗炎癥	2.8%	3.9%
厚壁菌群	誘發(fā)炎癥	83%	70%	增加	下降
變形菌

FindingBy

Alpha diversity（α多樣性）	Increased	Gao et?al. [19], Chang et?al. [14]
	Decreased	Fahlen et?al. [18], Alexseyenko et?al. [17], Tett et?al. [16]
Beta diversity（β多樣性）	Lower	Fahlen et?al. [18]
	Higher	Alexseyenko et?al. [17], Tett et?al. [16], Loeshe et?al. [12], Chang et?al. [14]
Phylum level
Firmicutes（厚壁菌門）	Increased?Firmicutes	Gao et?al. [19], Fahlen et?al. [18], Langan et?al. [10]
	Decreased?Firmicutes	Loeshe et?al. [12], Assarsson et?al. [13], Drago et?al. [15]
Actinobacteria（放線菌門）	Decreased?Actinobacteria	Gao et?al. [19], Fahlen et?al. [18], Langan et?al. [10]
	Increased?Firmicutes?and?Actinobacteria	Alexseyenko et?al. [17]
Proteobacteria(變形菌門)	Decreased?Proteobacteria(放形)	Gao et?al. [19]
	Increased?Proteobacteria	Fahlen et?al. [18], Drago et?al. [15]
Genus level
Streptococcus（鏈球菌門）	Increased?Streptococcus	Gao et?al. [19], Fahlen et?al. [18], Alexseyenko et?al. [17], Stehlikova et?al. [11], Drago et?al. [15]
	No correlation	Loeshe et?al. [12]
Staphylococcus（葡萄球菌）	Increased?Staphylococcus	Gao et?al. [19], Tett et?al. [16]
	Decreased?Staphylococcus	Fahlen et?al. [18]
Propionibacterium（丙酸桿菌）	Lower?Propionibacterium	Gao et?al. [19], Fahlen et?al. [18], Drago et?al. [15], Stehlikova et?al. [11], Loeshe et?al. [12]
Gram positives（革蘭氏陽性）	Increased relative abundance of combined Gram positives:?Corynebacterium,?Propionibacterium,?Staphylococcus, and?Streptococcus	Alexseyenko et?al. [17]
	Corynebacterium?and?Staphylococcus?were significantly correlated with PASI scores	Langan et?al. [10]
	Increased?S. aureus,?decreased?P. acne	Gao et?al. [19]
	Site-specific microbiota without related disease	Tett et?al. [16]

It has been reported that B. longum strains exert pro-differentiating, as well as and pro-regenerating, effects on primary human epidermal keratinocytes [68]

非常有意思，羅列了很多關于銀屑病患者中“菌門增加還是減少”的結果截然相反的論文。

上述內容來自【12】，【13】也包含一張類似的比較表格

Pro- and prebiotics are commonly used to modulate the microbiome by promoting the growth of specific species. Three studies using three distinct probiotic species affecting distinct pathways of the pathomechanism of psoriasis [61, 62] have all shown improvement in the course of the disease. The probiotics resulted in the improvement of epithelial barrier function, increased production of TNF-alpha by epithelial cells, and regulated activation of the NF-?β pathway [63]. An issue with probiotic supplementation is that the colonization of probiotic bacteria in the gut is mostly transient as they are only detectable for less than 2 weeks after cessation of intake [64]. However, a study by Maldonado-Gómez et al. demonstrated that a certain Bifidobacterium longum (B. longum) strain was able to persist for over 6 months in a subset of subjects where it was originally absent [65]. A recent, randomized, double-blind, placebo-controlled trial evaluated the effect of a probiotic mixture as co-adjutant treatment together with topical steroids in 90 patients with plaque psoriasis. The results showed a large reduction in the score of severity indexes in the probiotic group, compared with the placebo group. Gut microbiota analysis demonstrated the efficacy of the probiotic in modulation of the composition of the microbiota. After the end of the probiotic or placebo intake, patients were followed up for 6 months. The results showed a lower risk of relapse in patients in the probiotic group [66].（益生元和益生元通常用于通過促進特定物種的生長來調節(jié)微生物組。三項研究使用了三種不同的益生菌，它們影響銀屑病發(fā)病機制的不同途徑[61,62]，所有這些研究都表明銀屑病的病程有所改善。益生菌可改善上皮屏障功能，增加上皮細胞產生TNF-α，并調節(jié)NF-β途徑的激活[63]。益生菌補充的一個問題是，益生菌在腸道中的定植大多是短暫的，因為它們在停止攝入后的不到2周內才可檢測到[64]。然而，Maldonado-Gómez等人的一項研究表明，某種長雙歧桿菌（B.longum）菌株能夠在最初不存在的一部分受試者中持續(xù)6個月以上[65]。最近的一項隨機、雙盲、安慰劑對照試驗評估了益生菌混合物與局部類固醇聯(lián)合治療90例斑塊型銀屑病患者的療效。結果顯示，與安慰劑組相比，益生菌組的嚴重性指數得分大幅下降。腸道微生物群分析證明了益生菌在調節(jié)微生物群組成方面的功效。在服用益生菌或安慰劑結束后，對患者進行6個月的隨訪。）

上面的內容來自【13】

It is believed that, there are fractions ?of the ?gut microbiota with the ability to ?counteract inflammation(抵抗炎癥) (Bacteroidetes and Actinobacterial), and others that are more prone to induce inflammation (Firmicutes) （導致炎癥） and the disturbed microbiome ratio may be the cause for inducing psoriasis.?

he ?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).

人類腸道擬桿菌和厚壁菌占據其中98%

Firmicutes ?was ?the ?commonest ?detected phyla ?in ?psoriasis ?patients ?(83%), ?while ?Bacteroidetes and ?Actinobacterial ?phyla ?were ?accounted ?for ?9.2 ?and 2.8%, ?respectively. ? ?In ?the ?control ?group ?the ?detected percentage ?were ?70, ?22, ?and ?3.9% ?for ?Firmicutes, Bacteroidetes, ?and ?Actinobacterial ?phyla, ?respectively.(厚壁菌是銀屑病患者中最常見的菌門（83%），類桿菌和放線桿菌分別占9.2%和2.8%。在對照組中，厚壁菌門、擬桿菌門和放線菌門的檢出率分別為70%、22%和3.9%。)

上述內容來自【2】

In favoring an increased Firmicutes to Bacteroidetes ratio and reduced abundance of short-chain fatty acid–producing bacteria, sleep dysfunction could be contributing to worsening psoriasis and cardiometabolic comorbidities through intestinal dysbiosis. Future studies are needed to determine whether gut- and sleep-targeting interventions could be therapeutic in patients with psoriasis having poor sleep.

上述內容來自【5】

Background and Objective

Immunotherapy could change the complex host-microbial interactions. We aimed to investigate the dynamics of gut microbiome in response to secukinumab [an interleukin (IL)-17 inhibitor] and ustekinumab (an IL-12/23 inhibitor) therapy and its association with treatment response in psoriasis.

Methods

This observational, longitudinal study collected a total of 114 fecal samples from 12 healthy controls and 34 patients with psoriasis at baseline and 3 and 6?months after secukinumab (n?=?24) or ustekinumab treatment (n?=?10) and gut microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA.

Results

Secukinumab treatment causes more profound alterations in gut microbiome, including increases in the relative abundance of phylum?Proteobacteria?and decreases in?Bacteroidetes?and?Firmicutes, than ustekinumab treatment. The relative abundance of family?Pseudomonadaceae, family?Enterobacteriaceae?and order?Pseudomonadales?also increased significantly following secukinumab therapy. In contrast, there was no significant change in gut microbiome composition following ustekinumab treatment, and only genus?Coprococcus?significantly increased after 6?months of ustekinumab therapy. Moreover, we observed significant differences in baseline gut microbiome between responders and non-responders to secukinumab treatment.

Conclusion

These results indicate that gut microbiome is altered differently after anti-IL17 and anti-IL12/23 treatment. Secukinumab (anti-IL17) therapy is associated with distinct and more profound gut microbiome shifts than ustekinumab therapy (anti-IL 12/23) in patients with psoriasis. Moreover, gut microbiome would serve as potential biomarkers of response to secukinumab treatment.

上述內容來自【6】

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【3】中提到菌群比例不平衡導致了銀屑病

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An association between psoriasis and inflammation of the gut has also been observed; 7-11% of patients with inflammatory bowel disease (IBD) are also diagnosed with psoriasis. Further, the same pattern of dysbiosis (microbial imbalance) has been described in both IBD and psoriasis patients, regardless of whether the conditions are co-occurring. This dysbiosis has been shown to include a depletion in healthy bacteria, such as Lactobacillus spp., Bifidobacterium spp., and F. prausnitzii, as well as colonization of certain pathogenic bacteria, including E.coli and Salmonella sp. Additionally, evidence has shown that colonization of S. aureus, Malassezia, and C. albicans in the skin, gut, or both, exacerbates psoriasis.

?上面內容來自【4】

	銀屑病患者
Lactobacillus spp(雙歧桿菌)	下降
Bifidobacterium spp（乳酸桿菌）	下降
Feacalibacterium?prausnitzii	下降
雙歧桿菌	下降
金黃色葡萄球菌	如果上升（則加重）
馬拉色菌	如果上升（則加重）
白色念珠菌	如果上升（則加重）
丙酸桿菌	下降
鏈球菌	上升
棒狀桿菌	上升
葡萄球菌	上升

Psoriasis is a chronic, inflammatory immune-mediated skin disease that affects about 2% of the world’s population. In 20% of patients with psoriasis, the characteristic skin lesions are accompanied by psoriatic arthritis (PsA). Psoriasis arises in genetically predisposed individuals who have a dysregulated immune response to various environmental factors. The human body is home to many microbial species, and both the skin and the gut microbiome influence the development and function of immune tissue development and function. Studies on the cutaneous microbiome show a trend toward an increased relative abundance of Streptococcus and a decreased level of Propionibacterium in patients with psoriasis compared to healthy controls. In the gut microbiome, the ratio of Firmicutes and Bacteroidetes was perturbed in psoriatic individuals compared to healthy controls. Actinobacteria was relatively underrepresented in patients with psoriasis compared to healthy individuals. A decrease in skin microbiome flora diversity seems to be a sign that a patient with psoriasis is at elevated risk for developing arthritis. Modulating the skin microbiota for therapeutic reasons can be achieved by antimicrobial (antibiotic) therapy, the application of prebiotics or probiotics, or the transplantation of an entire healthy microbial population.

（銀屑病患者丙酸桿菌下降，鏈球菌豐度上升）

上述內容來自【10】

Curiously, studies in IBD also implicate these genera, with a decreased abundance of Ruminococcus and Akkermansia in both ulcerative colitis and Crohn disease27（瘤胃群菌和akk菌減少）【13】

Lower abundance of Propionibacterium in lesional skin was reported by Gao et al. [19], Fahlen et al. [18], Drago et al. [15], Stehlikova et al. [11], and Loeshe et al. [12], which is in contrast to Alexseyenko et al. [17] who reported an increase in the relative abundance of combined Gram positives such as Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus. In the subsequent study by Langan et al. [10], the presence of Corynebacterium and Staphylococcus was found to be significantly correlated with PASI scores while Anaerococcus and Propionibacterium were associated with non-lesional skin. These are consistent with the reports by Gao et al. [19] and Chang et al. [14] that at species level lesional skin psoriasis had an increased level of S. aureus but a decreased level of P. acne.（Gao等人[19]、Fahlen等人[18]、Drago等人[15]、Stehlikova等人[11]和Loeshe等人[12]報告了皮損皮膚中丙酸桿菌豐度較低的情況，這與Alexseyenko等人[17]報告的棒狀桿菌、丙酸桿菌等組合革蘭氏陽性菌相對豐度增加形成對比，葡萄球菌和鏈球菌。在Langan等人[10]的后續(xù)研究中，發(fā)現棒狀桿菌和葡萄球菌的存在與PASI評分顯著相關，而厭氧球菌和丙酸桿菌與非皮損皮膚相關。這與Gao等人[19]和Chang等人[14]的報告一致，即在物種水平上，皮損性銀屑病的金黃色葡萄球菌含量增加，但痤瘡桿菌含量減少。）

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Compelling new research from Spain demonstrates that the answer to this question may, in fact, lie within the gut. These researchers have demonstrated higher levels of a specific chemical, LPS, in the blood of patients with psoriasis who also have metabolic syndrome, an ever increasing situation here in America characterized by excess body fat, high blood sugar, elevated blood pressure, etc.

LPS happens to be a chemical that makes up part of the cell membrane of a large number of bacteria that live within the gut. Finding elevated LPS levels in the bloodstream is an indication of two things. First, it means that the gut has become permeable or leaky, which has allowed the LPS to get into the bloodstream. Second, it means that the process of inflammation has been enhanced as LPS acts as a powerful switch, turning on the inflammatory cascade.

What I found most compelling about the study was the fact that even when the skin condition improved using phototherapy, again a treatment based exclusively on dealing with the skin, the elevation of the LPS did not change. What this means is that the phototherapy was basically treating the smoke while the fire was being ignored. The fire is the inflammatory cascade brought on by this LPS chemical that leeches its way into the bloodstream because the gut is permeable.

So, you might then ask, what causes the gut to become permeable in the first place? Several important factors should be considered to answer this question. First and foremost, understand that it is the role of various probiotic bacteria to maintain the integrity of the gut lining. When the balance of bacteria within the gut is threatened by such things as overuse of antibiotics, or even dietary choices, the ability of the good bacteria to maintain the gut wall lining is challenged. In addition, it is known that gliadin, a protein found in gluten, may also threaten the integrity of the gut lining.

(光療法治標不治本，銀屑病本質是血液中LPS濃度的上升)

上述內容來自【7】

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The results from this promising animal model prompted a series of human studies. In one, administering medium-chain fatty acids as a prebiotic in healthy individuals appeared to diversify their gut microbiota and to expand the population of regulatory T cells in their blood. “We saw more bacteria overall, and in particular, more reportedly beneficial bacteria,” Dr. Scher says. “So now we have a proof of principle that a single modification correlates with an increase in your body’s inflammation regulators,” he says(中鏈脂肪酸所謂益生元能使得腸道菌群更加多樣化)

A Potential Explanation for IL-17i-Mediated Gut Inflammation
The same concept can be applied to other medications like the interleukin-17 inhibitor, or IL-17i. The drug class, commonly prescribed to patients with psoriatic arthritis and spondyloarthritis, has the well-known and seemingly paradoxical side effect of exacerbating Crohn’s disease in some patients.

At the gut level, research led by Julia Manasson, MD, post-doctoral T32 research fellow, and colleagues suggests significant shifts in the microbiota of patients with spondyloarthritis receiving IL-17i therapy, with some showing a significant increase in the abundance of Candida albicans yeast in the intestinal lumen. The same shift was not observed in patients receiving TNF blockade therapy. The increase, Dr. Scher says, may explain why certain patients who already have subclinical gut inflammation develop clinically overt inflammation and Crohn’s disease upon treatment with an IL-17 inhibitor.(其中一些患者的腸腔中白色念珠菌酵母菌的豐度顯著增加。在接受TNF阻斷治療的患者中未觀察到同樣的變化。Scher博士說，這種增加可能解釋了為什么某些已經患有亞臨床腸道炎癥的患者在使用IL-17抑制劑治療后會出現臨床上明顯的炎癥和克羅恩病)

上述內容來自【8】

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Food is one of the major modifiable factors regulating the gut microbiota, the community of microorganisms living in the intestines. Eating a Western diet can cause rapid change to the gut’s microbial community and its functions. This disruption in microbial balance—known as dysbiosis—contributes to gut inflammation.（西餐會迅速破壞腸道菌群）

上述內容來自【9】

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The two most dominant phyla in intestinal
microbiome are Bacteroidetes and Firmicutes [11]. Bacteria from these two phyla may
secrete short-chain fatty acids (SCFA), which are the end products of bacterial anaerobic
fermentation of dietary fibre. Many studies suggested that SCFA have anti-inflammatory
properties, can induce regulatory T cells in the colon and maintain its homeostasis, and are
able to modulate the function of intestinal macrophages [12]. A study conducted in 2011
by Arumugam et al. determined three robust clusters of intestinal microbiome, named
enterotypes, depending on dominant genera: enterotype 1—Bacteroides, enterotype 2—
Prevotella, enterotype 3—Ruminococcus. The most often occurring is enterotype three
which, besides Ruminococcus, also includes Akkermansia genus [13].

（腸道中兩個最主要的門

微生物群是擬桿菌和厚壁菌[11]。來自這兩個門的細菌可能

分泌短鏈脂肪酸（SCFA），這是細菌厭氧發(fā)酵的最終產物

膳食纖維的發(fā)酵。許多研究表明，SCFA具有抗炎作用

特性，可以誘導結腸中的調節(jié)性T細胞并維持其體內平衡，并且

能夠調節(jié)腸道巨噬細胞的功能[12]。2011年進行的一項研究

由Arumugam等人確定了三個強大的腸道微生物群，命名為

腸型，取決于優(yōu)勢屬：腸型1-類桿菌，腸型2-

普雷沃特菌，腸型3-瘤胃球菌。最常見的是腸三型

除瘤胃球菌外，還包括Akkermansia屬[13]）

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Treatments
According to Natural Medicine Journal, the first step is to treat the underlying cause of a leaky gut. For example, changes in diet that reduce gut inflammation due to Crohn’s disease or ulcerative colitis may improve intestinal barrier function.

Research shows the following treatments may help heal leaky gut:

antioxidant supplements, such as quercetin, Ginkgo biloba, vitamin C, and vitamin E
zinc supplementation with nutrients that support healthy intestinal mucosa, such as L-glutamine, phosphatidylcholine, and gamma-linolenic acid
plant enzymes
probiotics
dietary fiber
Eating healing foods is said to mend leaky gut. These can include:

bone broth
raw dairy products
fermented vegetables
coconut products
sprouted seeds
Speaking with your doctor
Despite the lack of evidence supporting this syndrome, there’s little doubt that it’s a real condition. Proponents of this syndrome are confident it’s only a matter of time before clear evidence confirms that it causes systemic health issues.（

根據《自然醫(yī)學雜志》，第一步是治療腸道滲漏的根本原因。例如，改變飲食以減少克羅恩病或潰瘍性結腸炎引起的腸道炎癥可能會改善腸道屏障功能。

研究表明，以下治療方法可能有助于治愈腸道滲漏：

抗氧化劑補充劑，如槲皮素、銀杏葉、維生素C和維生素E

補充營養(yǎng)素，如L-谷氨酰胺、磷脂酰膽堿和γ-亞麻酸，以支持健康的腸粘膜

植物酶

益生菌

膳食纖維

據說吃有治療作用的食物可以修復腸道的滲漏。這些措施可包括：

骨頭湯

生乳制品

發(fā)酵蔬菜

椰子制品

發(fā)芽種子

）

以上內容來自【14】

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One study described how administrating Lactobacillus pentosus GMNL-77 as a probiotic to psoriatic mice significantly reduced erythema, scaling, and epidermal thickening compared with mice in the control group. Another group of mice which received Lactobacillus reuteri（羅伊式乳桿菌） exhibited an accelerated wound healing time.（傷口愈合快）

A study conducted with humans diagnosed with severe pustular psoriasis emphasized the effectiveness of probiotic treatments in patients. Previously these patients were unresponsive to several treatments including steroids, dapsone, and methotrexate. However, “after initiating Lactobacillus sporogenes（芽孢乳酸桿菌） supplementation 3 times per day, the patients showed significant clinical improvement within 2 weeks, with almost complete remission after 4 weeks,” the authors said.（迅速緩解）【15】

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Psoriasis patients differ from controls in the observed community structure. The dominant phyla in psoriasis patients were Bacteroidetes 47.1%, Firmicutes 44.6%, Proteobacteria 5.4%, Actinobacteria 0.8% and Fusobacteria 0.7%, while the principal phyla found in controls were Bacteroidetes 59.9%, Firmicutes 33.0%, Proteobacteria 4.2%, Verrucomicrobia 1.4% and Actinobacteria 0.8% (Fig. 2).
?

	psoriasis	controls
Bacteroidetes	47.1%	59.9%
Firmicutes	44.6%	33.0%
Proteobacteria	5.4%	4.2%
Actinobacteria	0.8%	1.4%
Fusobacteria	0.7%	0.8%

The fact that most relevant genus in psoriasis patients that discriminated against non-psoriasis controls were Faecalibacterium and Blautia, taxa producing high levels of butyrate, contradicts the traditional association of butyrate producers observed in diseases such as IBD66,67. Therefore, results highlight the need for additional research given the observational nature and limits of 16S used in this study.

In our control group, the predominant genus were Bacteroides and Paraprevotella. These bacteria differ only in family (Bacteroideaceae for Bacteroides and Prevotellaceae for Paraprevotella)68,69. Increasing evidence proposes that Bacteroides harness complex recalcitrant glycans70. SCFAs are the major metabolic products of anaerobic fermentation of glycans by gut bacteria and have been shown to impact on the host physiology71. The beneficial effect of Bacteroides is consistent with our findings, where this genus was increased in controls and depleted in psoriasis patients.（

銀屑病患者中與非銀屑病對照組最相關的屬是糞便桿菌屬和Blautia屬，即產生高水平丁酸的分類群，這一事實與在IBD66、67等疾病中觀察到的丁酸產生者的傳統(tǒng)關聯(lián)相矛盾。因此，鑒于本研究中使用的16秒的觀測性質和局限性，研究結果強調了進行額外研究的必要性。

在我們的對照組中，主要屬為類桿菌和副雷沃桿菌。這些細菌僅在科（擬桿菌科為擬桿菌屬，Prevotellaceae為Pararevotella）68,69中有所不同。越來越多的證據表明類桿菌利用復雜的難降解聚糖70。SCFA是腸道細菌厭氧發(fā)酵聚糖的主要代謝產物，已被證明對宿主生理有影響71。類桿菌的有益作用與我們的研究結果一致，在對照組中，該屬菌數量增加，而在銀屑病患者中，該屬菌數量減少。

）

上面內容來自【17】

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For example, Lactobacillus rhamnosus GG, a commensal species, secretes p40, a protein that suppresses cytokine-mediated apoptosis and epithelial barrier disruption.[22]

Many studies on human and other animals mention that the intestinal microbiome's influence extends to extracolonic sites and contributes to the function, and dysfunction, of distant organ systems.[2,28] For instance, short-chain fatty acids (SCFAs), which are produced from dietary fibers fermented by the gut microbiome, have a protective role against the progression of some inflammatory disorders, including allergy and arthritis, in addition to colitis.（例如，鼠李糖乳桿菌GG，一種共生物種，分泌p40，一種抑制細胞因子介導的凋亡和上皮屏障破壞的蛋白質

許多關于人類和其他動物的研究提到，腸道微生物組的影響延伸到結腸外部位，并導致遠處器官系統(tǒng)的功能和功能障礙。[2,28]例如，短鏈脂肪酸（SCFA），由腸道微生物組發(fā)酵的膳食纖維產生，除結腸炎外，對某些炎癥性疾病的進展具有保護作用，包括過敏和關節(jié)炎。）

.[33] Another class of metabolites, SCFAs, regulates both the activation and apoptosis of immune cells（SCFA會調節(jié)細胞的激活和凋亡）

The beneficial effects of intestinal bacteria on skin health and appearance have been documented in several studies on rodents and humans. In rats, oral administration of Lactobacillus brevis SBC8803 resulted in decreased tone of cutaneous arterial sympathetic nerve and increased cutaneous blood flow.[37] Such effects were possibly caused by increased serotonin release from intestinal enterochromaffin cells followed by activation of parasympathetic pathways.[37] A considerable decrease in transepidermal water loss (TEWL), a marker of skin barrier function, was noted as well.[37] Noteworthy, similar outcomes were observed in human clinical research. After taking L. brevis SBC8803 orally for 12 weeks, human subjects had significantly decreased TEWL and increased corneal hydration.[38] In another study, it was shown that bacterial supplementation positively affects skin barrier function.[39]（腸道細菌對皮膚健康和外觀的有益影響已在幾項關于嚙齒動物和人類的研究中得到證實。在大鼠中，口服短乳桿菌SBC8803導致皮膚動脈交感神經張力降低和皮膚血流量增加。[37]這種效應可能是由腸嗜鉻細胞釋放的5-羥色胺增加，然后激活副交感神經通路引起的。[37]經皮皮膚失水（TEWL）顯著減少，這是皮膚屏障功能的標志。[37]值得注意的是，在人類臨床研究中也觀察到類似的結果。在口服短乳桿菌SBC8803 12周后，人類受試者的TEWL顯著降低，角膜水合作用增加。[38]另一項研究表明，補充細菌對皮膚屏障功能有積極影響。[39]）

Although the healing process through microscopic examination of wounds revealed the usual histomorphologic stages of wound healing in both probiotic-treated and untreated mice, the time required for complete healing was markedly reduced in the treated group（羅伊氏乳桿菌能加速皮損愈合）

Recently, after the discovery of elevated IL-17 levels in psoriatic lesions, therapies shifted the focus to Th17 cells. Cytokines released by Th17 cells promote the expression of the IL-10 cytokine family, including IL-20 and IL-22 cytokines, which causes keratinocyte hyperproliferation. After the discovery of the Th17 pathway, most clinical and mechanistic evidence indicate that psoriasis is primarily driven by the IL-23/IL-17/Th17 axis.[63,64,65,66,67,68,69](最近，在銀屑病皮損中發(fā)現IL-17水平升高后，治療的重點轉移到Th17細胞。Th17細胞釋放的細胞因子促進IL-10細胞因子家族的表達，包括IL-20和IL-22細胞因子，導致角質形成細胞過度增殖。在發(fā)現Th17通路后，大多數臨床和機制證據表明銀屑病主要由IL-23/IL-17/Th17軸驅動)

Faecalibacterium prausnitzii, a beneficial microbial inhabitant of the large intestine, provides many benefits to the host. It serves as a significant source of 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.[75,76] This species is much less abundant in the gut of psoriatic patients than in healthy ones.[77] Furthermore, intestinal dysbiosis generates endotoxin-peptidoglycan superantigens that induce autoimmune and inflammatory conditions associated with psoriasis. An immune response is triggered in response to the toxins produced by microorganisms in the gut and psoriatic patients exhibit positive skin test to gut bacterial antigens.(prausnitzii糞桿菌是大腸中有益的微生物，為宿主提供許多益處。它是丁酸的重要來源，丁酸是一種SCFA，為結腸細胞提供能量，減少氧化應激，并通過觸發(fā)調節(jié)性T細胞發(fā)揮抗炎作用，從而賦予免疫耐受性在胃腸道系統(tǒng)之外。[75,76]銀屑病患者腸道中的該物種數量遠少于健康患者.此外，腸道生態(tài)失調產生內毒素肽聚糖超抗原，誘導銀屑病相關的自身免疫和炎癥條件。對腸道微生物產生的毒素會觸發(fā)免疫反應，銀屑病患者對腸道細菌抗原的皮膚試驗呈陽性)

Probiotics and psoriasis
Although data on probiotic supplementation in psoriasis treatment are limited, promising outcomes have been documented. Psoriasis is often associated with intestinal inflammation, such as IBD, the pathophysiology is closely associated with the dysbiosis of the gut.[90] Moreover, a recent study showed that psoriasis has been associated with gut dysbiosis.[91] One study was shown that Lactobacillus pentosus GMNL-77 administration (as a probiotic) in an imiquimod-induced psoriasis mouse model results in significantly less erythema, scaling, and epidermal thickening when compared with untreated control mice.[41] In another study, the same probiotic suppressed the expression of TNF-α, IL-6, and proinflammatory cytokines in the IL-23/IL-17 cytokine axis.[92] Though the mechanism for reduced T-cell activity was unclear, the authors proposed that this effect was mediated by the suppression of CD103+ dendritic cells, intestinal antigen-presenting cells that modulate regulatory T cells in the GI tract.[93] Furthermore, in a placebo-controlled study of psoriasis patients, Bifidobacterium infantis 35624 supplementations led to significantly decreased plasma levels of TNF-α when compared with the placebo group.[92] The effectiveness of probiotic treatment was highlighted in a case severe pustular psoriasis that had been unresponsive to steroids, dapsone, and methotrexate. After initiating Lactobacillus sporogenes supplementation 3 times per day, the patients showed significant clinical improvement within 2 weeks, with almost complete remission after 4 weeks.[94](雙歧桿菌+戊糖乳桿菌)

More than 70 clinical studies on food containing microbial ingredients have been conducted to investigate the potential side effects of probiotics and none has shown any adverse effects.[97]（已經對含有微生物成分的食品進行了70多項臨床研究，以調查益生菌的潛在副作用，但沒有發(fā)現任何副作用。）調查益生菌副作用的文章是下面一篇

Use of probiotics in pediatrics: rationale, mechanisms of action, and practical aspects - PubMed

上述內容來自【18】

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Recently, a study focused on autism and accompanying GI symptoms12, found that autism patients had a distinct and less diverse gut microbial composition with lower levels of Prevotella, Coprococcus, and an unclassified Veillonellaceae. All these results suggest a potentially important role of the gut microbiome in illnesses that are not directly related to the digestive tract.（孤獨癥患者的腸道菌群多樣性較低）

The intestinal bacterial composition was compared based on BT detection and enterotype classification (Arumugam et al.)13: enterotype 1 (predominance of Bacteroides, Fig. 2A), enterotype 2 (predominance of Prevotella) (Fig. 2B) and enterotype 3 (predominance of Ruminococcus) (Fig. 2C)

腸型分類：

	主要細菌
腸型1	類桿菌
腸型2	普氏桿菌
腸型3	瘤胃球菌

Butyrate and propionate are short chain fatty acids produced by gut microbial and with a demonstrated anti-inflammatory role19 and, furthermore, butyrate has shown to be a key-player for maintaining barrier integrity20.（腸道需要丙酸鹽和丁酸鹽來抗炎）

上述內容來自【19】

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In particular, the relationship between psoriasis and obesity is bidirectional, with obesity favoring psoriasis and psoriasis predisposing individuals to obesity (Shipman and Millington, 2011; Cooksey et al., 2018; Dauden et al., 2018). (肥胖有利于銀屑病)

S. aureus, another common pathogen, may also be a pathogenic factor of psoriasis, given the increase in Th17 polarization and exacerbated cutaneous inflammation during early colonization of newborn mouse skin (Chang et al., 2018).（Th17極化增加，皮膚炎癥加劇）

上述內容來自【20】

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A 2018 study looked at the effects of probiotics on skin conditions such as eczema in mice.

The researchers found that certain probiotics reduced and may even prevent chronic skin inflammation, including:

Lactobacillus salivarius LA307(唾液乳桿菌)
Lactobacillus rhamnosus LA305（鼠李糖乳桿菌）

Another study in mice considered the effects of Lactobacillus pentosus GMNL-77 on psoriasis. The authors found that this strain prevented skin inflammation and reduced biomarkers of inflammation.（戊糖乳桿菌GMNL-77）

yogurt（奶繞）
kefir, which is a fermented, probiotic dairy drink
kombucha, a fermented tea made with bacteria and yeast
fermented cheeses
pickles
miso, a Japanese seasoning paste（其實就是國內豆瓣醬，但是國內的豆瓣醬太咸了，不利于健康） made with fermented soybeans
fermented vegetables, such as kimchi and sauerkraut
Probiotic supplements are another good option

Treatments for mild to moderate outbreaks include:

topical corticosteroids
topical retinoids, which contain vitamin A
vitamin D analogs, which contain a topical synthetic form of vitamin D
salicylic acid
coal tar（水楊酸、維生素D）

Research suggests that probiotics may reduce symptoms of psoriasis. However, probiotics are still not well understood, and they can harm people with weakened immune systems.

Confirming the benefits and risks of taking probiotics will require further research.

Everyone’s microbiome is unique, so a person may need a particular combination of probiotic strains. Consult a healthcare provider before taking probiotic supplements.

Probiotic supplements are available for purchase online.（益生菌可能傷害免疫系統(tǒng)薄弱的人，目前人類依然沒有很好地理解益生菌，所以一個人可能需要一種特殊的益生菌菌株組合）

上述內容來自【21】

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In mice with an experimental model of psoriasis induced by imiquimod, oral treatment with broad-spectrum antibiotic reduces the severity of skin inflammation through downregulation of Th17 immune response [12,13]. （光譜抗生素能抑制Th17）

We searched four electronic databases from their inception to March 2020: MEDLINE (via PubMed), Embase (via OvidSP), Web of Science Core Collection, and Scopus（作者提到了自己的電子數據庫）

All studies confirmed the association of psoriasis and gut microbiota dysbiosis. At the phylum level,?Bacteroidetes?had a lower relative abundance and?Firmicutes?a higher relative abundance in patients with psoriasis than in healthy controls [20,22,23]. However, in a study by Huang et al.,?Bacteroidetes?was reported to be increased and?Firmicutes?decreased in psoriasis [21]. Additionally, two studies showed decreased amounts of?Proteobacteria?in psoriatic cohort [20,22]. Studies for?Actinobacteria?provide conflicting results—an increase in two studies [20,22] and decrease in the other two studies [27,28].

At the family level, the relative abundance of?Ruminococcaceae,?Lachnospiraceae,?Clostridiales Family XIII,?Peptostreptococcaceae,?Enterococcaceae,?Coriobacteriaceae, and?Eggerthellaceae?was increased in psoriasis, whereas?Prevotellaceae,?Barnesiellaceae,?Tannerellaceae,?Rikenellaceae,?Porphyromonadaceae,?Marinifilaceae,?S24-7,?Lactobacillaceae,?Streptococcaceae,?Pasteurellaceae,?Burkholderiaceae,?Desulfovibrionaceae,?Victivallaceae, and?Verrucomicrobiaceae?decreased. There were conflicting results for?Bacteroidaceae,?Erysipelotrichaceae,?Veillonellaceae?and Bifidobacteriaceae. Some studies reported these families to be decreased in psoriasis [22,23,28] while others showed their increase [22,25].

At the genus level,?Paraprevotella,?Barnesiella,?Alistipes,?Allobaculum,?Coprobacillus,?Carnobacterium,?Granulicatella,?Rothia,?Gordonibacter,?Thermus?were found to be decreased. Following genera were relatively increased in psoriasis:?Ruminococcus,?Subdoligranulum,?Blautia,?Coprococcus,?Dorea,?Christensenella,?Streptococcus,?Lactococcus,?Enterococcus,?Bacillus,?Collinsella,?Slackia. Divergent findings were reported for?Bacteroides,?Parabacteroides,?Faecalibacterium,?Lachnospira,?Akkermansia,?Sutterella, and?Bifidobacterium.

At the species level,?Prevotella copri,?Faecalibacterium prausnitzii?and?Akkermiansia muciniphila?were found to be significantly decreased, while?Ruminococcus gnavus,?Dorea formicigenerans,?Clostridium citroniae,?Escherichia coli, and?Collinsella aerofaciens?were increased in patients with psoriasis compared to control group. However, these alterations have not been confirmed in more than one study. Details indicating the altered bacteria are shown in?Table 4.

（

所有研究都證實了銀屑病與腸道微生物群失調的關系。在門水平上，銀屑病患者的類桿菌相對豐度低于健康對照組，厚壁菌相對豐度高于健康對照組[20,22,23]。然而，Huang等人的一項研究表明，銀屑病患者類桿菌增多，厚壁菌減少[21]。此外，兩項研究表明銀屑病隊列中的變形菌數量減少[20,22]。對放線菌的研究提供了相互矛盾的結果：兩項研究[20,22]增加，另兩項研究[27,28]減少。

在家族水平上，銀屑病患者的反芻菌科、絲狀菌科、梭狀芽孢桿菌科、消化鏈球菌科、腸球菌科、科里奧巴氏菌科和蛋殼菌科的相對豐度增加，而普雷沃菌科、巴氏菌科、單寧菌科、里肯菌科、卟啉單胞菌科、海洋菌科、S24-7、乳酸桿菌科、，鏈球菌科、巴氏桿菌科、伯克霍爾德菌科、脫硫弧菌科、維克托菌科和疣狀菌科減少。對于類桿菌科、丹毒菌科、脈內爾菌科和雙歧桿菌科，結果存在矛盾。一些研究報告這些家族在銀屑病[22,23,28]中有所減少，而另一些則顯示其增加[22,25]。

在屬水平上，發(fā)現副革蘭氏菌、巴氏桿菌、阿利斯蒂普斯菌、異桿菌、糞桿菌、肉桿菌、顆粒桿菌、羅氏菌、戈登桿菌、熱桿菌數量減少。銀屑病中的以下屬相對增多：瘤胃球菌、鼻下角膜炎、布勞提氏菌、糞球菌、Dorea、Christensenella、鏈球菌、乳球菌、腸球菌、芽孢桿菌、柯林斯菌、松馳菌。對于類桿菌、類副桿菌、糞桿菌、拉奇諾匹拉菌、阿克曼菌、蘇特萊拉菌和雙歧桿菌，報告了不同的發(fā)現。

在物種水平上，發(fā)現銀屑病患者與對照組相比，copri普氏菌、prausnitzii糞桿菌和粘質Akkermianiasia顯著減少，而gnavus瘤胃球菌、Dorea formicigeneras、檸檬酸梭菌、大腸桿菌和產氣柯林斯菌增加。然而，這些改變尚未在一項以上的研究中得到證實。表4顯示了改變細菌的詳細信息。）

文中的Table4提供了一張有矛盾的研究結果的列表

We presented several taxa that differed in their relative abundance in psoriasis. For instance, a reduction in Bacteroides and Proteobacteria with increased proportions of Firmicutes and Actinobacteria, at phylum level was reported in more than one study. These four phyla constitute?>?98% of the gut microbiota. Therefore, the Firmicutes/Bacteroidetes (F/B) ratio is considered as an important marker of gut microbiota state. Several studies have shown that an altered F/B ratio in gut microbiome is associated with psoriasis comorbidities, such as cardiovascular diseases [34], obesity [35], insulin resistance [36] and nonalcoholic fatty liver disease [37]. Only one study by Huang et al. reported opposite changes in Bacteroides and Firmicutes [21]. This dissimilarity partially may be related to a small number of participants and very diverse group, which consisted of people with plaque psoriasis, pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis.

The tendencies for the change of Firmicutes and Bacteroidetes in patients with psoriasis are also present at the lower taxonomic levels. Families Bacteroidaceae and Prevotellaceae are two important subgroups in phylum Bacteroides. While alterations in Bacteroidaceae and Bacteroides have been confirmed in psoriasis, there is no agreement about the direction of these changes. Similarly, the role of these bacteria is also controversial. Bacteroides fragilis, can produce enterotoxins responsible for inflammation and impairment of the intestinal barrier [38]

（我們介紹了銀屑病中幾個相對豐度不同的分類群。例如，不止一項研究報告了類桿菌和變形桿菌的減少，以及厚壁菌門和放線菌門的比例增加。這四個門構成?>?98%的腸道微生物群。因此，厚壁菌/擬桿菌（F/B）比率被認為是腸道微生物群狀態(tài)的重要標志。幾項研究表明，腸道微生物群中F/B比率的改變與銀屑病共病有關，如心血管疾病[34]、肥胖[35]、胰島素抵抗[36]和非酒精性脂肪肝[37]。只有Huang等人的一項研究報告了類桿菌和厚壁菌的相反變化[21]。這種差異部分可能與少數參與者和非常多樣化的群體有關，其中包括斑塊型銀屑病、膿皰型銀屑病、紅皮病型銀屑病和銀屑病關節(jié)炎患者。

銀屑病患者厚壁菌和類桿菌的變化趨勢也存在于較低的分類水平。類桿菌科和類桿菌科是類桿菌門的兩個重要亞類。雖然類桿菌科和類桿菌科的改變已在銀屑病中得到證實，但這些改變的方向尚不一致。同樣，這些細菌的作用也存在爭議。脆弱類桿菌可產生腸毒素，導致腸道屏障的炎癥和損傷[38]）

Regarding the second important phylum, Firmicutes, at least two studies have found increased abundance of families Ruminococcaceae and Lachnospiraceae, with depletion of Faecalibacterium prausnitzii and augmentation of Ruminococcus gnavus at the species level. F. prausnitzii metabolites exert a protective effect on the gut barrier and inhibit the activation of the NF-κB, altering the pro-inflammatory response [43]. The depletion of F. prausnitzii has been associated with inflammatory disorders, such as inflammatory bowel disease or ankylosing spondylitis [26,39]. On the other hand, R. gnavus produces an inflammatory polysaccharide and contributes to gut barrier dysfunction. Its increased abundance was observed in inflammatory bowel disease, spondyloarthritis, eczema and coronary artery disease [44].

It is still not clear whether psoriasis is an effect or a cause of the observed disbalance between beneficial and pathogenic microbes.（關于第二個重要的門，厚壁菌門，至少有兩項研究發(fā)現，瘤胃球菌科和拉克諾菌科的數量增加，在物種水平上，prausnitzii糞桿菌的減少和gnavus瘤胃球菌的增加。F.prausnitzii代謝物對腸道屏障具有保護作用，并抑制NF-κB的激活，從而改變促炎癥反應[43]。prausnitzii的缺失與炎癥性疾病有關，如炎癥性腸病或強直性脊柱炎[26,39]。另一方面，gnavus弧菌產生一種炎性多糖并導致腸道屏障功能障礙。在炎癥性腸病、脊椎關節(jié)炎、濕疹和冠狀動脈疾病中觀察到其含量增加[44]。

目前尚不清楚銀屑病是有益微生物和致病微生物之間失衡的結果還是原因。）

上述內容來自【22】

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Reference:

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

【2】(PDF) Gut bacterial microbiota in psoriasis: A case control study

【3】Microbiome make-up linked to risk of leaky gut in people with psoriasis

【4】Back to basics: Psoriasis - The Secret Life Of Skin

【5】Sleep and the Gut Microbiome in Psoriasis: Clinical Implications for Disease Progression and the Development of Cardiometabolic Comorbidities - Bridget Myers, Vidhatha Reddy, Nicholas Brownstone, Stephanie Chan, Quinn Thibodeaux, Hsin-Wen Chang, Tina Bhutani, Wilson Liao, 2021

【6】Gut Microbiome in Psoriasis is Perturbed Differently During Secukinumab and Ustekinumab Therapy and Associated with Response to Treatment | SpringerLink

【7】Psoriasis – A Gut Related Disorder - David Perlmutter M.D.

【8】Using the Microbiome to Aid Psoriatic & Rheumatoid Arthritis Diagnostics & Therapeutics | NYU Langone News

【9】Psoriasis, Autoimmunity, Inflammation and the Gut – what natural things can you do to heal? | Clinical Education

【10】The Microbiome in Psoriasis and Psoriatic Arthritis: The Skin Perspective | The Journal of Rheumatology

【11】Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients | BMC Microbiology | Full Text

【12】Skin and Gut Microbiota in Psoriasis: A Systematic Review | IntechOpen

Role of skin and gut microbiota in the pathogenesis of psoriasis, an inflammatory skin disease - ScienceDirect

【13】The Microbiome in Psoriasis and Psoriatic Arthritis: Joints | The Journal of Rheumatology

【14】What’s the Connection Between Leaky Gut Syndrome and Psoriasis?

【15】Smoking, Periodontitis Linked With Increased Risk of Psoriasis

【16】Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index

【17】Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index | Scientific Reports

【18】The role of gut microbiome in the pathogenesis of psoriasis and the therapeutic effects of probiotics【19】Gut microbial composition in patients with psoriasis

【20】

Frontiers | Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies | Microbiology

【21】Can probiotics help with psoriasis?

【22】Gut Microbiome in Psoriasis: An Updated Review

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