Keystone gut microbiota promoting pathobiont clearance by nutrition competition and microbiota recovering

Karina Xavier

/Oeiras [PO]

The mammalian gut microbiota plays a pivotal role in various aspects of host health, ranging from nutrition, immune system maturation, and protection against intestinal pathogens. Many environmental factors can influence the composition and function of the gut microbiota. Notably, antibiotic treatments can inadvertently perturb the gut microbiota, rendering the host more susceptible to infections and chronic inflammation. While studying mechanisms underlying microbiota recovery after the cessation of antibiotic treatment, we identified a non-pathogenic Klebsiella gut microbe capable of restoring colonization resistance against Enterobacteriaceae following antibiotic treatment. This particular non-pneumonia Klebsiella species represents a keystone member of the mammalian gut microbiota found in both mice and humans. In wild-type mice, our studies demonstrated that this bacterium was sufficient for providing colonization resistance against Escherichia coli K-12 and delayed the colonization of Salmonella Typhimurium through a mechanism of nutritional competition (as detailed in Oliveira et al., Nature Microbiology, 2020). Building on this foundation, we are now expanding our research to explore the potential use of this Klebsiella strain as a next-generation probiotic.
Our latest findings show that in a mouse model of inflammatory bowel disease, this keystone Klebsiella accelerates the clearance of Adherent and Invasive (AIEC) E. coli. It achieves this by promoting the recovery of butyrate-producing bacteria and preventing inflammation. These results underscore the importance of identifying microbes with critical microbiota functions and their potential use in developing strategies to facilitate microbiota recovery following antibiotic treatments.

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