Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid

Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. Data availability statement: The data of RNAseq and 16 S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.