Aging-Induced Dysbiosis of Gut Microbiota as a Risk Factor for Increased Infection.

Invasive foodborne infection causes gastroenteritis, septicemia, meningitis, and chorioamnionitis, and is associated with high case-fatality rates in the elderly. It is unclear how aging alters gut microbiota, increases risk of listeriosis, and causes dysbiosis post-infection. We used a geriatric murine model of listeriosis as human surrogate of listeriosis for aging individuals to study the effect of aging and infection. Aging and listeriosis-induced perturbation of gut microbiota and disease severity were compared between young-adult and old mice. Young-adult and old mice were dosed intragastrically with . Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher colonization in liver, spleen, and feces. Metagenomics analyses of fecal DNA-sequences showed increase in α-diversity as mice aged, and infection reduced its diversity. The relative abundance of major bacterial phylum like, and remained stable over aging or infection, while the phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in and bacteria even before infection when compared to uninfected young-adult mice.  infection increased the abundance of and in young-adult mice, while members of the and family were significantly increased in old mice. The abundance of the genera and were significantly reduced post-infection in young-adult and in old mice as compared to their uninfected counterparts. Butyrate producing, immune-modulating bacterial species, like and were significantly increased only in old infected mice, correlating with increased intestinal inflammatory mRNA up-regulation from old mice tissue. Histologic analyses of gastric tissues showed extensive lesions in the -infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like , , and were only abundant in infected young-adult mice but their abundance diminished in the infected old mice. Listeriosis in old mice enhances the abundance of butyrate-producing inflammatory members of the / bacteria while reducing/eliminating beneficial commensals in the gut. Results of this study indicate that, aging may affect the composition of gut microbiota and increase the risk of invasive infection.