AUTHOR=Alam Mohammad S. , Gangiredla Jayanthi , Hasan Nur A. , Barnaba Tammy , Tartera Carmen 

TITLE=Aging-Induced Dysbiosis of Gut Microbiota as a Risk Factor for Increased Listeria monocytogenes Infection

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.672353

DOI=10.3389/fimmu.2021.672353

ISSN=1664-3224

ABSTRACT=<p>Invasive foodborne <italic>Listeria monocytogenes</italic> 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 <italic>L. monocytogenes</italic> 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 <italic>L. monocytogenes</italic>. Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher <italic>Listeria</italic> 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, <italic>Bacteroidetes</italic> and <italic>Firmicutes</italic> remained stable over aging or infection, while the <italic>Verrucomicrobia</italic> phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in <italic>Clostridaiceae</italic> and <italic>Lactobacillaceae</italic> bacteria even before infection when compared to uninfected young-adult mice. <italic>L. monocytogenes</italic> infection increased the abundance of <italic>Porphyromonadaceae</italic> and <italic>Prevotellaceae</italic> in young-adult mice, while members of the <italic>Ruminococcaceae</italic> and <italic>Lachnospiraceae</italic> family were significantly increased in old mice. The abundance of the genera <italic>Blautia</italic> and <italic>Alistipes</italic> 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 <italic>Pseudoflavonifractor</italic> and <italic>Faecalibacterium</italic> 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 <italic>Listeria</italic>-infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like <italic>Lactobacillus</italic>, <italic>Clostridiales</italic>, and <italic>Akkermansia</italic> 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 <italic>Ruminococcaceae</italic>/<italic>Lachnospiraceae</italic> 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 <italic>L. monocytogenes</italic> infection.</p>