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Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity.

Published version
Peer-reviewed

Type

Article

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Authors

Sovran, Bruno 
Hugenholtz, Floor 
Elderman, Marlies 
Van Beek, Adriaan A  ORCID logo  https://orcid.org/0000-0003-0786-1682
Graversen, Katrine 

Abstract

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.

Description

Keywords

Aging, Animals, Gastrointestinal Microbiome, Intestinal Mucosa, Male, Mice, Mice, Inbred C57BL, Muramidase, Paneth Cells, Ribonuclease, Pancreatic, T-Lymphocytes, Transcriptome

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

9

Publisher

Springer Science and Business Media LLC