Aging Increases the Severity of Colitis and the Related Changes to the Gut Barrier and Gut Microbiota in Humans and Mice

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Abstract

This study aims to compare intestinal mucosal barrier function in older and young ulcerative colitis (UC) patients and the healthy population, and to explore the possible mechanisms through which aging increases the severity of colitis in mice. The old healthy group showed discontinued tight junction (TJ) strand. The E-cadherin and occludin protein expressions in the colonic tissue of the old healthy subjects were lower than those in the younger healthy people. The protein expressions of E-cadherin and occludin were lower in the old UC patients than in the younger UC patients. In mice, disease activity indexes induced by inflammatory stimulus differed as a function of age. Weight loss level, histological scores, and expression of proinflammatory factors were higher in the dextran sulfate sodium (DSS)-induced group of aged mice than in the young DSS-induced mice. Compared with the results observed in the young DSS-induced mice, the protein expressions of E-cadherin and occludin in the aged DSS-induced mice were lower. Furthermore, significant differences were observed in the composition of the gut microbiota between the young and aged mice. In the aged mice, the fraction of beneficial bacteria (Lactobacillus) was lower before the DSS treatment, while the fraction of the harmful bacteria (Turicibacter, Parasutterella) was higher than that observed in the young mice. After the DSS treatment in the aged mice, the fraction of beneficial bacteria (Odoribacter and Alistipes) was lower, while the fraction of harmful bacteria (Turicibacter) was higher than in the young mice. We demonstrate that the aging of the human colon is characterized by an impairment of the intestinal barrier. Aging leads to more severe disease following DSS challenge. Age-related deterioration of gastrointestinal barrier function and gut microbial dysbiosis may be involved in the pathogenesis of colitis in the aged mice.

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