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Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity
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Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity
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Journal Article
Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 14/63
/ 38
/ 38/61
/ 82/51
/ Age
/ Aging
/ Chair Nutrition Metabolism and Genomics
/ HNE Nutrition, Metabolism and Genomics
/ HNE Voeding, Metabolisme en Genomics
/ Humanities and Social Sciences
/ Immunity
/ Laboratorium voor Microbiologie
/ Leerstoelgroep Celbiologie en immunologie
/ Leerstoelgroep Host Microbe Interactomics
/ Lysozyme
/ Mucosa
/ Mucus
/ Nutrition, Metabolism and Genomics
/ Science
/ Villus
/ VLAG
/ Voeding, Metabolisme en Genomica
/ WIAS
