Abstract
BackgroundThe gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging.ResultsHere, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy.ConclusionsIn conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing.DWzth9x4bNysC3Pe8t3wT_Video abstract
Highlights
Health span is determined by the interactions between genetic and environmental factors [1, 2]
We compared the gut microbiome of C57BL/6J mice at week 1 (W1), 4 (W4), 20 (W20), 50 (W50) and 100 (W100) to determine the differences in the gut microbiome composition according to ageing (Fig. 2a, b)
Upon visualizing β-diversity (Fig. 2c and Fig. S2) with PERMANOVA of principal coordinate analysis (PCoA), we identified a differential clustering of W1, W4, W20, W50 and W100
Summary
Health span is determined by the interactions between genetic and environmental factors [1, 2]. Shin et al Microbiome (2021) 9:240 permeability due to deterioration of the intestinal barrier function enhances the changes in the composition of intestinal bacteria and the production of bacteria-derived substances and causes systemic inflammation in a selfsustaining loop [5] Both humans and laboratory animal models considerably alter the composition of intestinal bacteria as ageing progresses, and these changes affect the health and longevity of the host [6]. The outer membrane protein AMUC_1100 of AK improves gut barrier function and reduces endotoxemia in obese mice by stimulating TLR2 signalling [11] These studies have suggested that beneficial commensals, such as Akkermansia, Bifidobacterium and Christensenellaceae, can be used as probiotics to improve various age-related symptoms [12]. Prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging
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