Sex steroids, namely androgens and estrogens, modulate physiology, development, and reproduction of animals. Biosynthesis of C₁₈ estrogens proceeds through the removal of the C-19 angular methyl group from C₁₉ androgens, resulting in the formation of an aromatic A-ring. This aromatization proceeds through the oxidative bond cleavage between steroidal C-10 and C-19, which is catalyzed by an aromatase at the cost of NADPH and O₂. The reverse reaction (from estrogens to androgens) is thermodynamically challenging and has not been reported in any organisms.

In the past decade, Dr. Yin-Ru Chiang and his research team at the Biodiversity Research Center focused on anaerobic steroid metabolism in bacteria. Their previous study published in Frontiers in Microbiology indicated that anaerobic bacteria are able to transform androgens into estrogens through oxygenase-independent pathway. Recently, they found that anaerobic bacteria are able to transform estrogens into androgens through a cobalamin-dependent methylation. Furthermore, they identified the corresponding genes and proposed biochemical mechanisms involved in the retroconversion of estrogens into androgens. The identification of the cobalamin-dependent estrogen methylation reaction thus represents an unprecedented metabolic link between cobalamin and steroid metabolism. This study has been recently published in Proceedings of the National Academy of Sciences of the United States of America (abbreviation: PNAS) on 21 January, 2020. Article website: https://www.pnas.org/content/117/3/1395.

Moreover, this research article was highlighted by PNAS with the Commentary entitled: Anaerobic bacteria need their vitamin B₁₂ to digest estrogen.

It was thought that steroid hormones are exclusively produced by animals; thus, in biogeochemistry, steroids are used as biomarkers specific for eukaryotes. For the first time, Dr. Chiang and his research team demonstrated that interconversion between estrogen and androgen readily occurs in the anaerobic biosphere. Human gut is a complicated anaerobic ecosystem. Recently, numerous studies have suggested that gut microbiota may affect the sex steroid profile in the host. However, the key bacterial players and the mechanisms involved remain to be investigated. Therefore, the occurrence of retroconversion of estrogens into androgens in bacteria portends unexplored microbe-host metabolic interdependencies via this cobalamin-dependent estrogen methylation reaction. Dr. Chiang and his research team are attempting to isolate and to characterize the gut anaerobes capable of interconversion of sex steroids.

In the future, these sex steroids-transforming anaerobes isolated from human gut may be used as probiotics to facilitate the homeostasis of sex hormones in human beings.