Microbial evolutionary signatures associated with longevity in the gut of very old mice

Abstract

Aging is accompanied by numerous events, including an increase in inflammation and gut dysbiosis.This contributes to aging by increasing intestinal permeability and inflammation, but how it influencesmicrobiota evolution and pathobiont selection remains unknown. Here we approach this question bycomparing microbial evolution in the guts of three sets of mice: young (6-9 weeks old), old (19 monthsold), and very old (25 months old).Previous studies have described the adaptation of a commensal strain of E. coli to the guts of younganimals and shown that it acquires metabolic-related mutations whereas, in old mice, the pattern shiftstowards stress-related mutations, and metabolic adaptations arise slower.Yet, aging is a discontinuous process and as such, other age groups should also be characterized. So,we compared frailty, intestinal inflammation, and microbiota composition of very old animals to youngerones. These were the frailest but not more locally inflamed than the old. Interestingly, compared withthe others, they showed an increase in health-associated bacteria, e.g. Akkermansia muciniphila, and E.coli displayed more metabolic than stress-related mutations, resembling young animals. These data suggest that microbiota alterations during aging may not be exclusively dysbiotic and maybe associated with longevity.