New research shows that hydrogen sulphide (H2S), a microbial gas produced in the colon by sulphate-reducing bacteria (SRB), can directly stimulate the release of glucagon-like peptide 1 (GLP1; an incretin hormone involved in glucose homeostasis and appetite regulation) from enteroendocrine L cells in the gastrointestinal tract. The findings support the increasingly recognized role of the gut microbiota and its metabolites as key regulators of host metabolism.

As high concentrations of H2S are produced in the vicinity of GLP1-secreting L cells, Jeffrey Gagnon and colleagues were interested in potential crosstalk between H2S and GLP1. The team treated mouse L cells (the GLUTag cell line) with a H2S donor (NaHS or GYY4137) and found that GLP1 secretion was increased approximately twofold compared with vehicle-treated cells.

To confirm the findings in vivo, C57BL/6 male mice were fed a diet low in fermentable carbohydrate with or without the prebiotic chondroitin sulphate for 4 weeks. Chondroitin sulphate treatment increased the abundance of the SRB Desulfovibrio piger in faeces and faecal and colonic levels of H2S. Moreover, this increase in H2S-producing bacteria was accompanied by enhanced GLP1 and insulin secretion, improved oral glucose tolerance and reduced food consumption.

Although absolute proof that H2S-producing bacteria can stimulate GLP1 secretion will require confirmatory studies in germ-free mice given a defined probiotic that contains SRB, Gagnon is optimistic about the findings so far. “The compound we used, chondroitin sulphate, is a relatively affordable natural health product that is currently used in the treatment of arthritis,” he explains. “If future work can demonstrate a similar enhancement of GLP1 levels in humans, chondroitin sulphate could become a useful tool to treat obesity and type 2 diabetes mellitus.”