“Meta-omics” analyses have greatly expanded our understanding of gut microbiota composition, metabolism, and links to disease. However, identifying the specific roles and impacts of individual microbes remains difficult. For pathogens, Koch’s postulates still serve as the standard to establish causality. Proving beneficial effects of commensals is harder, as these microbes are typically present in healthy individuals. Colonization resistance against enteric infections arises from host-microbiota interactions, but the complexity of the gut ecosystem makes it challenging to attribute specific functions to individual strains. To address this, we developed the Oligo-Mouse-Microbiota (Oligo-MM; OMM12), a defined community of 12 bacterial strains isolated from mice that stably colonizes germ-free mice and confers intermediate resistance to pathogens like Salmonella Typhimurium and Clostridioides difficile. This model enables testing whether additional microbes, identified via metagenomics and obtained from culture collections, contribute to protection. Overall, the Oligo-MM is a versatile system for applying Koch’s postulates to beneficial microbes, facilitating the study of host-microbe and microbe-microbe interactions and advancing our understanding of gut ecology and disease mechanisms.
Publications:
Intestinal colonization resistance in the context of environmental, host, and microbial determinants. Woelfel S, Silva MS, Stecher B. Cell Host Microbe. 2024 Jun 12;32(6):820-836. doi: 10.1016/j.chom.2024.05.002
Establishing causality in Salmonella-microbiota-host interaction: The use of gnotobiotic mouse models and synthetic microbial communities. Stecher B. Int J Med Microbiol. 2021 Apr;311(3):151484. doi: 10.1016/j.ijmm.2021.151484.
Eberl C, Weiss AS, Jochum LM, Durai Raj AC, Ring D, Hussain S, Herp S, Meng C, Kleigrewe K, Gigl M, Basic M, Stecher B. E. coli enhance colonization resistance against Salmonella Typhimurium by competing for galactitol, a context-dependent limiting carbon source. Cell Host Microbe. 2021 Sep 29:S1931-3128(21)00420-0. doi: 10.1016/j.chom.2021.09.004.
Herp S, Brugiroux S, Garzetti D, Ring D, Jochum LM, Beutler M, Eberl C, Hussain S, Walter S, Gerlach RG, Ruscheweyh HJ, Huson D, Sellin ME, Slack E, Hanson B, Loy A, Baines JF, Rausch P, Basic M, Bleich A, Berry D, Stecher B. Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis. Cell Host Microbe. 2019 May 8;25(5):681-694. doi.org/10.1016/j.chom.2019.03.004
Brugiroux S., Beutler M., Pfann C., Garzetti D., Ruscheweyh H.J., Ring D., Diehl M., Herp S., Lötscher Y., Hussain S., Bunk B., Pukall R., Huson D.H., Münch P.C., McHardy A.C., McCoy K.D., Macpherson A.J., Loy A., Clavel T., Berry D., Stecher B. Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium. Nat Microbiol. 2016 Nov 21;2:16215. doi: 10.1038/nmicrobiol.2016.215.
