Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity
Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity
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DOI：
10.1038/s41598-018-35228-3
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发表时间：
2019-02-05
影响因子：
4.6
通讯作者：
Wells, Jerry M.
中科院分区：
文献类型：
--
作者：
Sovran, Bruno;Hugenholtz, Floor;Wells, Jerry M.
衰老显著增加了胃肠道（GI）疾病的易感性，但很少有研究调查影响胃肠道的衰老关键因素。为了解决这一知识差距，我们使用了10周龄和19个月大的同窝小鼠来研究微生物群和宿主基因表达与衰老相关的变化。在老年小鼠中，结肠粘液层的厚度相对于年轻小鼠减少约6倍，并且更容易被管腔细菌穿透。这与隐窝上部杯状细胞凋亡增加有关。小肠粘液的屏障功能也受到损害，并且经常观察到微生物群与绒毛上皮接触。抗微生物潘氏细胞因子Ang4和溶菌酶的表达量显着减少。这些屏障缺陷伴随着粪便微生物群的重大变化，并显著降低了嗜粘蛋白阿克曼氏菌的丰度，该菌受到人类老年的强烈和负面影响。转录组学显示，年龄相关的免疫和其他基因在肠粘膜组织中的表达减少，包括T细胞特异性转录和T细胞信号通路的减少。我们在老年人肠道中观察到的生理和免疫变化可能会产生肠道以外的重大后果。
Aging significantly increases the vulnerability to gastrointestinal (GI) disorders but there are few studies investigating the key factors in aging that affect the GI tract. To address this knowledge gap, we used 10-week- and 19-month-old litter-mate mice to investigate microbiota and host gene expression changes in association with ageing. In aged mice the thickness of the colonic mucus layer was reduced about 6-fold relative to young mice, and more easily penetrable by luminal bacteria. This was linked to increased apoptosis of goblet cells in the upper part of the crypts. The barrier function of the small intestinal mucus was also compromised and the microbiota were frequently observed in contact with the villus epithelium. Antimicrobial Paneth cell factors Ang4 and lysozyme were expressed in significantly reduced amounts. These barrier defects were accompanied by major changes in the faecal microbiota and significantly decreased abundance of Akkermansia muciniphila which is strongly and negatively affected by old age in humans. Transcriptomics revealed age-associated decreases in the expression of immunity and other genes in intestinal mucosal tissue, including decreased T cell-specific transcripts and T cell signalling pathways. The physiological and immunological changes we observed in the intestine in old age, could have major consequences beyond the gut.