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Pathogenicity of Commensal Gut Biofilm In Prefrail Aging
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International audience. Abstract Achieving healthy aging is a global challenge requiring a deeper understanding of aging mechanisms, spanning from robustness to frailty. Although age-related alteration of the gut microbiome (microb-aging) is well studied, there is a lack of research investigating the gut microbiota during the early stages of prefrailty and understanding its behavior within the context of a natural community lifestyle, in interaction with host tissue. Therefore, we used fecal samples from the human aging cohort INSPIRE-T, to characterize polymicrobial biofilms. Intestinal tissues and feces from an aging mouse cohort were also used. Food supplement was tested for potential geroprotective effects on biofilms. Findings pointed to taxonomic and physical alterations, increased instability, and virulence with regards to intestinal epithelium, for biofilms of prefrail individuals, compared to their age-matched robust counterparts. Multiparametric analyses further linked biofilm characteristics to clinical traits, suggesting that biofilm culture could be a proxy tool for evaluating a healthy or unhealthy aging status. Exposure of biofilms to the grape pomace prebiotic partially reversed the prefail biofilm phenotype. In aged mice with prefrailty, but not in robust aged mice, gut microbiota biofilm structure was altered and caused colon damage when transplanted into antibiotic-depleted mice. These findings suggest a causal link between microb-aging in prefrailty and gut inflammation, advocating microbiota-targeted therapies to reverse prefrail phenotype and thereby promote healthspan.
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