The distinct composition of the gut microbiota in each individual results in variable metabolic activity and output of these communities, which influences the host, including resistance to enteric pathogens. Lack of reproducibility in biomedical research is nowadays frequently attributed to the microbiota, but little is known about which specific members and metabolites contribute to disease severity. Here, we use genetically identical mouse lines with variable microbiota compositions on a standardized diet and observed highly variable colonization with the enteric pathogen Citrobacter rodentium without antibiotics intervention. We found the same differences in formerly germ-free animals harbouring the respective donors microbiota and also in vitro by coculturing cecal bacteria from resistant and susceptible animals with C. rodentium showing that the phenotype is fully dependent on differences in the microbiota. We analysed the microbiome composition and found a higher abundance of butyrate-producing bacteria as well as increased levels of butyrate in resistant mice. By supplementation of susceptible and germ-free animals with butyrate, we could significantly lower the levels of colonization highlighting that commensal-derived primary and secondary bacterial metabolites are highly variable between laboratory animals from different vendors and are potent modulators of hosts susceptibility to infection with C. rodentium.
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Lisa Osbelt, Sophie Thiemann, Nathiana Smit, Till Robin Lesker, Madita Schröter, Eric J. C. Gálvez, Kerstin Schmidt-Hohagen, Marina C. Pils, Sabrina Mühlen, Petra Dersch, Karsten Hiller, Dirk Schlüter, Meina Neumann-Schaal, Till Strowig March 24, 2020