The microbiota confers colonization resistance, which blocks Salmonella gut colonization1. As diet affects microbiota composition, we studied whether food composition shifts enhance susceptibility to infection. Shifting mice to diets with reduced fibre or elevated fat content for 24 h boosted Salmonella Typhimurium or Escherichia coli gut colonization and plasmid transfer. Here, we studied the effect of dietary fat. Colonization resistance was restored within 48 h of return to maintenance diet. Salmonella gut colonization was also boosted by two oral doses of oleic acid or bile salts. These pathogen blooms required Salmonella’s AcrAB/TolC-dependent bile resistance. Our data indicate that fat-elicited bile promoted Salmonella gut colonization. Both E. coli and Salmonella show much higher bile resistance than the microbiota. Correspondingly, competitive E. coli can be protective in the fat-challenged gut. Diet shifts and fat-elicited bile promote S. Typhimurium gut infections in mice lacking E. coli in their microbiota. This mouse model may be useful for studying pathogen–microbiota–host interactions, the protective effect of E. coli, to analyse the spread of resistance plasmids and assess the impact of food components on the infection process.
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16S rRNA raw reads have been deposited at the European Nucleotide Archive (ENA) with accession no. PRJEB33890. All other data needed to evaluate the conclusions in this Article are presented in the paper or the Supplementary Information. Any additional data can be requested from the corresponding author.
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We thank members of the Hardt laboratory and R. Stocker for helpful scientific discussions and the RCHCI staff (especially K. Holzinger, D. Mollenhauer and S. Nowok) for excellent support of our animal work. E.S. is supported by the Swiss National Science Foundation (SNF, Marie Heim-Vögtlin award PMPDP3_158364 and Ambizione award PZ00P3_136742) and the Gebert Rüf ‘Microbials’ programme (GRS-073/17). W.-D.H. is supported by the SNF (310030_153074 and 310030B_173338/1; Sinergia CRSII_154414/1; NRP 72 407240-167121), ETH Zurich (ETH-33 12-2), the Novartis Freenovation Programme and the Promedica Foundation. S.S. is supported by ETH Zurich and the Helmut Horten Foundation. E.B. is supported by a Boehringer Ingelheim Fonds PhD Stipend and E.G. by a grant from the Monique Dornonville de la Cour Foundation. B.S. is supported by the German Research Foundation (STE 1971/4-2 SPP 1656/2) and the German Center for Infection Research (DZIF).
The authors declare no competing interests.
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Wotzka, S.Y., Kreuzer, M., Maier, L. et al. Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice. Nat Microbiol 4, 2164–2174 (2019). https://doi.org/10.1038/s41564-019-0568-5