ESPE Yearbook of Paediatric Endocrinology

Brief Summary:This study using mice and human models, shows that human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert biliary corticoids into progestins through 21-dehydroxylation. It thereby shows that a class of immuno- and metabo-regulatory steroids are transformed into a class of sex hormones and neurosteroids. It also illustrates that gut hydrogen gas production is essential and sufficient to support this metabolic pathway, which is more prominent in late pregnancy.

It is known that bacteria living in symbiosis with the human organism (‘the microbiome’) can interact positively or negatively with various organ functions. It was known that the gut microbiome interacts with host-produced steroids, but the mechanisms and physiological impact of such interactions was largely unknown. Correlations were previously described between gut microbiome, host phenotypes, and levels of sex- and stress-related steroid hormones. These authors now find historical evidence that specific strains of the gut microbiota can convert the glucocorticoids found in human bile into progestins (via 21-dehydroxylation).

This finding is important as it demonstrates that biliary secretion of glucocorticoid may not only be a negligible metabolic road to dispose of steroids (99% of steroids are disposed in urine), but may serve as important substrates for the production of functionally active progestins, including sex steroids and neurosteroids. It also establishes an important role for (bacterial) fermentation and H2 production in modulating steroid metabolism in the gut. Furthermore, it adds evidence that during pregnancy steroid metabolic pathways are regulated differently. Thus, this study opens a novel chapter of the, so far hidden, contribution of the human gut microbiome as an endocrine organ. Bioactive metabolites produced by gut bacteria may modulate hormonal homeostasis and signaling processes in health and disease.

A commentary was published on this study for its relevance in the field of endocrinology.

Reference: 1. Progestin production by the gut microbiota. Greenhill, C. Nat Rev Endocrinol 20, 446 (2024). doi: 10.1038/s41574-024-01013-8.