中文字幕在线免费网站，中文字幕高清在线免费播放，中文字幕在线免费看线人，中文字幕在线观看，在线的，免费网站永久入口视频，中文字幕，视频w日本m免费2019中文字幕乱码免费,在线视频，在线永久地址视频2019，中文字幕视频免费2019，2019中文文字在线高清视频MV，中文字幕在线视频，中文字幕在线2019，中文字幕在线看线人动作大片， 亚洲文字幕，在线中文字幕100页， 日本中文字幕视频网址，中文字幕在线观看视频，免费视频， 亚洲永久免费中文字幕，中文字幕永久视频在线，国产中文字幕在线视频，中文字母在线免费观看视频网站，中文 在线 免费，2019亚洲影视中文字幕，中文字幕AV免费看网站，无中文字幕免费，视屏，在线观看中文字幕，中文字慕视频在线免费，亚洲视频在线播放网站，中文字幕在线观看线人，中文字摹在线观看，免费在线视频中文字幕，中日韩高清视频免费看，中文字幕组在线观看，在线观看，中文字幕在线免费视频，中文乱码字视频在线，亚洲视频中文永久网，在线，无人区中文字幕高清，中文字幕视频网站，亚洲视频在线观看中文字幕，中文字在线视频，最新国产中文字幕2019，在线观看免费中文字幕，日中文字幕，观看视频，亚洲高清在线观看视频，中文字幕永久免费在线观看，亚洲视频网站网址，中文在线中文a，中文字在线乱码，免费中文字幕，中文字幕在线，快手网红福利费在线观看，中文字幕在线免费，字幕网在线观看入口，日本中文字幕作品在线播放，字幕在线免费网站，中文字幕永久有效，中文字幕2019，中文乱码永久播放视频||www.fsqpc.cn,寡妇高潮一级毛片免费看,亚洲精品www久久久久久,亚洲日韩精品欧美一区二区一,久久久久久高清一级毛片免费,久久久久天堂亚洲AV无码社区||www.mohair.com.cn ,2021久久精品国产99国产精品-小说区 亚洲 自拍 另类-日韩亚洲av无码一区二区不卡-精品无码一区二区三区爱欲九九-国产乱人伦精品一区二区在线观看||www.olyouxi.cn ,粉嫩虎白女在线观看中国女_天天摸日日碰天天看_国产在线v欧美在线TV_国产伦人人人人人人性||www.zhlslm.cn

Food Science and Human Wellness

Volume 12, Issue 5, September 2023, Pages 1526-1537

Yang Liu , Qing Liu , Chengcheng Zhang , Jianxin Zhao , Hao Zhang , Wei Chen , Qixiao Zhai

Abstract
Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes (such as COG0438, COG0463, and COG2244) related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.

Keywords
Akkermansia muciniphilaIntestinal barrierStrain specificityComparative genomicsBacterial surface components

1. Introduction
The integrity of the gut barrier is crucial for the maintenance of the health of the host [1]. Pathogens and harmful substances pass through the lumen and translocate to the bloodstream by increasing intestinal permeability induced by gut barrier impairment [2]. Recent surveys have shown that intestinal barrier dysfunction is closely associated with several diseases, including enteropathy [3], neurodegeneration [4], and metabolic disorders [5]. Based on several gene-knockout mice studies, spontaneous intestinal inflammation is caused by intestinal barrier dysfunction [6], [7], [8]. Notably, a number of studies suggest that impaired gut barrier was associated with the progression of inflammatory bowel disease (IBD) [9], [10]. Despite the obscurity of the causal relationship, intestinal barrier dysfunction is considered to exacerbate the progression of IBD, and maintenance of gut barrier function has been reported to inhibit proinflammatory cascades and physiological oxidative stress, which will ultimately contribute to maintaining intestinal homeostasis and tolerance in host-intestinal microbiota interactions [11]. A recent review summarized that dietary factors such as phenolic compounds (including resveratrol, curcumin, and quercetin) could improve the integrity of the gut barrier of animals with intestinal inflammation, which may be explained by the reduction of the release of proinflammatory factors, the enhancement of the expression of tight proteins, and an increase in the antioxidant activity of enterocytes [12]. Moreover, the treatment of the gastrointestinal tract area with drugs, such as prucalopride [13] and ghrelin [14], significantly reduces inflammation in the colons of mice by improving gut barrier function. Therefore, it is necessary to find an effective treatment for the recovery of barrier integrity loss.

Akkermansia muciniphila has been widely recognized as one of the most promising next-generation probiotics. The abundance of this bacterium is inversely associated with a series of dysfunctions including appendicitis [15], hypertension [16], autism [17], and IBD [18]. Chelakkot et al. [19] demonstrated that supplementation of the extracellular vesicles of A. muciniphila markedly reduced weight and improved glucose tolerance in obese mice. Lower insulin resistance and adipose tissue inflammation were also observed in diet-induced diabetic mice after the treatment with A. muciniphila [20]. One of the key mechanisms for the probiotic function of A. muciniphila is based on its regulation of the host intestinal barrier, thereby inhibiting the entry of intestinal bacteria-borne endotoxin into the blood and relieving chronic inflammation in vivo [21]. Several animal studies have indicated that A. muciniphila has beneficial effects on the secretion of antimicrobial peptides and mucin in intestinal epithelial cells [22], [23]. Kang et al. [24] reported that oral administration of A. muciniphila significantly reversed the inflammatory infiltration of colon tissue and the alterations in the expression tight junctions in dextran sodium sulphate (DSS)-induced mice. Based on a clinical trial, treatment with pasteurized A. muciniphila enhanced the gut barrier function of volunteers, which showed a reduced endotoxin level in plasma and an alleviated overweight or insulin resistance [25].

However, several studies have shown strain-specific effects on intestinal barrier regulation of intestinal microorganisms. Escherichia coli Nissle 1917 supplementation is effective against inflammatory factors secreted by immune cells in multiple sclerosis mice and further repairs intestinal permeability disorders [26]. Conversely, adherent-invasive E. coli strains have been reported to disrupt epithelial mitochondrial networks and increase gut permeability [27]. Toxigenic Bacteroides fragilis impairs gut barrier integrity and induces colon tumorigenesis by activating nuclear factor-kappa B (NF-κB) signaling in colonic epithelial cells [28], while non-toxigenic B. fragilis administration reduces intestinal permeability and alleviates bacteria-driven chronic colitis and tumors [29]. Limited by the isolation and incubation methods necessary for A. muciniphila, the strain-specific effect of this bacterium on intestinal functions has not received much attention. Zhai et al. [30] demonstrated that compared to the A. muciniphila ATCC-BAA835 strain, oral administration of A. muciniphila 139 strain showed a more significant reduction in proinflammatory cytokines expression, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, thus reversing disease symptoms in colitic mice. Moreover, it is noteworthy that although A. muciniphila could accelerate intestinal stem cell-mediated epithelial development, the AK32 strain, not the ATCC-BAA835 strain, exhibited better probiotic effects [22]. Thus, we hypothesized that different A. muciniphila strains may possess strain-specific effects on the integrity of the gut barrier.

The aim of this study was, therefore, to evaluate the effects of six A. muciniphila strains on gut barrier dysfunction, with a focus on mouse and Caco-2 cell line models. Furthermore, we sought to gain insight into the possible material basis for the action of A. muciniphila through comparative genomic analysis and the isolation and verification of specific bacterial components.

………………

文獻(xiàn)鏈接：https://www.sciencedirect.com/science/article/pii/S2213453023000228