Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa

Francois Blachier (1) , Mireille Andriamihaja (1) , Pierre Larraufie (1) , Eunyeong Ahn (2) , Annaig Lan (1) , Eunjung Kim (2)

1 PNCA (UMR 0914) - Physiologie de la Nutrition et du Comportement Alimentaire
2 Catholic University of Daegu

Among bacterial metabolites, hydrogen sulfide (H2S) has received increasing attention. The epithelial cells of the large intestine are exposed to two sources of H2S. The main one is the luminal source that results from specific bacteria metabolic activity towards sulfur-containing substrates. The other source in colonocytes is from the intracellular production mainly through cystathionine beta-synthase (CBS) activity. H2S is oxidized by the mitochondrial sulfide oxidation unit, resulting in ATP synthesis, and thus establishing this compound as the first mineral energy substrate in colonocytes. However, when the intracellular H2S concentration exceeds the colonocyte capacity for its oxidation, it inhibits the mitochondrial respiratory chain, thus affecting energy metabolism. Higher luminal H2S concentration affects the integrity of the mucus layer and displays pro-inflammatory effects. However, a low/minimal amount of endogenous H2S exerts an anti-inflammatory effect on the colon mucosa pointing out the ambivalent effect of H2S depending on its intracellular concentration. Regarding colorectal carcinogenesis, forced CBS expression in late adenoma-like colonocytes increased their proliferative activity, bioenergetics capacity, and tumorigenicity; while genetic ablation of CBS in mice resulted in a reduced number of mutagen-induced aberrant crypt foci. Activation of endogenous H2S production and low H2S extracellular concentration enhance cancerous colorectal cells proliferation. Higher exogenous H2S concentrations markedly reduce mitochondrial ATP synthesis and proliferative capacity in cancerous cells, enhance glycolysis, but do not affect their ATP cell content nor viability. Thus, it appears that, notably through an effect on colonocyte energy metabolism, endogenous and microbiota-derived H2S are involved in the host intestinal physiology and physiopathology.

Mots clés: hydrogen sulfide; energy metabolism; inflammatory bowel diseases; colorectal carcinogenesis

Domaines: Biologie animale

Francois Blachier, Mireille Andriamihaja, Pierre Larraufie, Eunyeong Ahn, Annaig Lan, et al.. Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa. AJP - Gastrointestinal and Liver Physiology, 2021, 320 (2), pp.G125-G135. ⟨10.1152/ajpgi.00261.2020⟩. ⟨hal-03033013⟩