Physiological Determinants Of Microbial Sulfidogenesis In The Intestinal Environment

H2S is an ambivalent molecule produced by commensal gut bacteria but also by the human host. It has detrimental impact on gut epithelial barrier during intestinal inflammation but also manifold beneficial functions. Intestinal H2S production by the microbiota is dependent on the type of inorganic or organic sulfur compound used as nutrient source and their metabolic interactions.

Aim: Define the physiological boundaries at which microbial H2S production becomes harmful to the host by revealing the sulfur source-dependent physiology of H2S-producing key human gut species under different biotic (varying microbial complexity) and abiotic conditions (oxidative stress, diet).

Approach: Physiological experiments with human gut isolates (mono- and co-cultures) and in vitro incubations of human feces. Diet-experiments with gnotobiotic mice having a defined microbiota with or without sulfidogens. Microbiota and metabolic analyses by amplicon sequencing, RT-qPCR, FISH, (meta)transcriptomics, metabolite and redox potential measurements, microsensors, and stable isotope probing. Analyses of gut barrier function and host sulfur metabolism.

Relevance: This project will show how dietary nutrients, redox conditions, and syntrophic interactions determine microbial sulfidogenesis in the gut and impact the host.

Student: Julia Krasenbrink

Faculty: Alexander Loy (PI), David Berry, Monika Bright, Jillian Petersen, Thomas Rattei

Funding: FWF doc.fund project MAINTAIN

Selected Publications:

Barton, L. L., Ritz, N. L., Fauque, G. D. & Lin, H. C. Sulfur Cycling and the Intestinal Microbiome. Dig. Dis. Sci. 62, 2241–2257 (2017).

Wang, R. Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed. Physiol. Rev. 92, 791–896 (2012).

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 2, 16215 (2016).

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