Dietary amino acids regulate Salmonella colonization via microbiota-dependent mechanisms in the mouse gut

Joseph M. Pickard, Steffen Porwollik, Gustavo Caballero-Flores, Roberta Caruso, Shinji Fukuda, Tomoyoshi Soga, Naohiro Inohara, Michael McClelland and Gabriel Núñez ()
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Joseph M. Pickard: University of Michigan Medical School
Steffen Porwollik: University of California, Irvine, School of Medicine
Gustavo Caballero-Flores: University of Michigan Medical School
Roberta Caruso: University of Michigan Medical School
Shinji Fukuda: Keio University, Tsuruoka
Tomoyoshi Soga: Keio University, Tsuruoka
Naohiro Inohara: University of Michigan Medical School
Michael McClelland: University of California, Irvine, School of Medicine
Gabriel Núñez: University of Michigan Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract The gut microbiota confers host protection against pathogen colonization early after infection. Several mechanisms underlying the protection have been described, but the contributions of nutrient competition versus direct inhibition are controversial. Using an ex vivo model of Salmonella growth in the mouse cecum with its indigenous microbes, we find that nutrient limitation and typical inhibitory factors alone cannot prevent pathogen growth. However, the addition of certain amino acids markedly reverses the microbiota’s ability to suppress pathogen growth. Enhanced Salmonella colonization after antibiotic treatment is ablated by exclusion of dietary protein, which requires the presence of the microbiota. Thus, dietary protein and amino acids are important regulators of colonization resistance.

Date: 2025
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DOI: 10.1038/s41467-025-59706-1

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