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dc.contributor.authorOsbelt, Lisa
dc.contributor.authorThiemann, Sophie
dc.contributor.authorSmit, Nathiana
dc.contributor.authorLesker, Till Robin
dc.contributor.authorSchröter, Madita
dc.contributor.authorGálvez, Eric J C
dc.contributor.authorSchmidt-Hohagen, Kerstin
dc.contributor.authorPils, Marina C
dc.contributor.authorMühlen, Sabrina
dc.contributor.authorDersch, Petra
dc.contributor.authorHiller, Karsten
dc.contributor.authorSchlüter, Dirk
dc.contributor.authorNeumann-Schaal, Meina
dc.contributor.authorStrowig, Till
dc.date.accessioned2020-04-07T12:17:36Z
dc.date.available2020-04-07T12:17:36Z
dc.date.issued2020-03-24
dc.identifier.citationPLoS Pathog. 2020 Mar 24;16(3):e1008448. doi: 10.1371/journal.ppat.1008448.en_US
dc.identifier.pmid32208465
dc.identifier.doi10.1371/journal.ppat.1008448
dc.identifier.urihttp://hdl.handle.net/10033/622224
dc.description.abstractThe composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease severity is largely unknown. Using isogenic mouse lines harboring distinct microbiota communities, we observed highly variable disease kinetics of enteric Citrobacter rodentium colonization after infection. Transfer of communities from susceptible and resistant mice into germ-free mice verified that the varying susceptibilities are determined by microbiota composition. The strongest differences in colonization were observed in the cecum and could be maintained in vitro by coculturing cecal bacteria with C. rodentium. Cohousing of animals as well as the transfer of cultivable bacteria from resistant to susceptible mice led to variable outcomes in the recipient mice. Microbiome analysis revealed that a higher abundance of butyrate-producing bacteria was associated with the resistant phenotype. Quantification of short-chain fatty acid (SCFA) levels before and after infection revealed increased concentrations of acetate, butyrate and propionate in mice with delayed colonization. Addition of physiological concentrations of butyrate, but not of acetate and/or propionate strongly impaired growth of C. rodentium in vitro. In vivo supplementation of susceptible, antibiotic-treated and germ-free mice with butyrate led to the same level of protection, notably only when cecal butyrate concentration reached a concentration higher than 50 nmol/mg indicating a critical threshold for protection. In the recent years, commensal-derived primary and secondary bacterial metabolites emerged as potent modulators of hosts susceptibility to infection. Our results provide evidence that variations in SCFA production in mice fed fibre-rich chow-based diets modulate susceptibility to colonization with Enterobacteriaceae not only in antibiotic-disturbed ecosystems but even in undisturbed microbial communities. These findings emphasise the need for microbiota normalization across laboratory mouse lines for infection experiments with the model-pathogen C. rodentium independent of investigations of diet and antibiotic usage.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleVariations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production.en_US
dc.typeArticleen_US
dc.identifier.eissn1553-7374
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstraße 7, 38124 Braunschweig, Germany.en_US
dc.identifier.journalPLoS pathogensen_US
dc.source.volume16
dc.source.issue3
dc.source.beginpagee1008448
dc.source.endpage
refterms.dateFOA2020-04-07T12:17:37Z
dc.source.journaltitlePLoS pathogens
dc.source.countryUnited States


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