Impact of grape polyphenols on Akkermansia muciniphila and the gut barrier.

Impact of grape polyphenols on Akkermansia muciniphila and the gut barrier.
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DOI:
10.3934/microbiol.2022035
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发表时间:
2022
期刊:
影响因子:
4.8
通讯作者:
Roopchand D
Roopchand D
中科院分区:
其他
文献类型:
--
作者:
Mezhibovsky E;Wu Y;Bawagan FG;Tveter KM;Szeto S;Roopchand D

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健康的胃肠道起到了高度选择性屏障的作用,允许吸收营养物质和代谢物,同时防止肠道细菌和其他外来化合物进入宿主循环和组织。肠道上皮和肠道粘液提供了抵御寄生微生物、病原体和外来有毒化合物的第一道物理防线。先前的研究表明,肠道微生物Akkermansia visiniPhila是一种粘蛋白代谢物,可以刺激肠道粘蛋白厚度,改善肠道屏障的完整性。研究发现,富含B型原花青素(PAC)化合物的葡萄多酚(GP)提取物可以增加粘液拟青霉的相对丰度,这表明PAC改变了肠道微生物区系,以支持健康的肠道屏障。为进一步研究GPs对小鼠肠道屏障和粘液嗜血杆菌的影响,将雄性C57BL/6小鼠分为高脂饲料(HFD)和低脂饲料(LFD)两组,分别饲喂含或不含1%Gps的高脂饲料(HFD-GP,LFD-GP)12周。与未添加饲料的小鼠相比,添加GP的小鼠表现出粪便和盲肠粘液金黄色葡萄球菌的相对丰度增加,细菌总数减少,结肠粘液层减少,粪便粘液含量增加。补充GP也减少了杯状细胞的存在,而不考虑饮食中的脂肪。与HFD组相比,HFD-GP组回肠内毒素结合蛋白(LBP)的基因表达减少,提示循环中的内毒素减少。尽管结肠粘液层被耗尽,但四组之间的炎症标志物(IFNG、IL1b、TNFa和NOS2)相似,只是LFD-GP组的回肠IL6mRNA水平低于LFD组。我们的发现表明,GP诱导的粘液阿司匹林的增加促进了肠道粘液层向肠腔的重新分布,而GP诱导的细菌总数的减少导致了较少的炎性肠道环境。
A healthy gastrointestinal tract functions as a highly selective barrier, allowing the absorption of nutrients and metabolites while preventing gut bacteria and other xenobiotic compounds from entering host circulation and tissues. The intestinal epithelium and intestinal mucus provide a physical first line of defense against resident microbes, pathogens and xenotoxic compounds. Prior studies have indicated that the gut microbe Akkermansia muciniphila, a mucin-metabolizer, can stimulate intestinal mucin thickness to improve gut barrier integrity. Grape polyphenol (GP) extracts rich in B-type proanthocyanidin (PAC) compounds have been found to increase the relative abundance of A. muciniphila, suggesting that PACs alter the gut microbiota to support a healthy gut barrier. To further investigate the effect of GPs on the gut barrier and A. muciniphila, male C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD) with or without 1% GPs (HFD-GP, LFD-GP) for 12 weeks. Compared to the mice fed unsupplemented diets, GP-supplemented mice showed increased relative abundance of fecal and cecal A. muciniphila, a reduction in total bacteria, a diminished colon mucus layer and increased fecal mucus content. GP supplementation also reduced the presence of goblet cells regardless of dietary fat. Compared to the HFD group, ileal gene expression of lipopolysaccharide (LPS)-binding protein (Lbp), an acute-phase protein that promotes pro-inflammatory cytokine expression, was reduced in the HFD-GP group, suggesting reduced LPS in circulation. Despite depletion of the colonic mucus layer, markers of inflammation (Ifng, Il1b, Tnfa, and Nos2) were similar among the four groups, with the exception that ileal Il6 mRNA levels were lower in the LFD-GP group compared to the LFD group. Our findings suggest that the GP-induced increase in A. muciniphila promotes redistribution of the intestinal mucus layer to the intestinal lumen, and that the GP-induced decrease in total bacteria results in a less inflammatory intestinal milieu.
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