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

Bruno Sovran, Floor Hugenholtz, Marlies Elderman, Adriaan A. Van Beek, Katrine Graversen, Myrte Huijskes, Mark V. Boekschoten, Huub F.J. Savelkoul, Paul De Vos, Jan Dekker, Jerry M. Wells

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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.

Original languageEnglish
Article number1437
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 5 Feb 2019

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Microbiota
Mucus
Immunity
Paneth Cells
T-Lymphocytes
Goblet Cells
Muramidase
Intestines
Gastrointestinal Tract
Mucous Membrane
Epithelium
Apoptosis
Bacteria
Gene Expression
Genes

Cite this

Sovran, Bruno ; Hugenholtz, Floor ; Elderman, Marlies ; Van Beek, Adriaan A. ; Graversen, Katrine ; Huijskes, Myrte ; Boekschoten, Mark V. ; Savelkoul, Huub F.J. ; De Vos, Paul ; Dekker, Jan ; Wells, Jerry M. / Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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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.",
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Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity. / Sovran, Bruno; Hugenholtz, Floor; Elderman, Marlies; Van Beek, Adriaan A.; Graversen, Katrine; Huijskes, Myrte; Boekschoten, Mark V.; Savelkoul, Huub F.J.; De Vos, Paul; Dekker, Jan; Wells, Jerry M.

In: Scientific Reports, Vol. 9, No. 1, 1437, 05.02.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Graversen, Katrine

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