The gut-microbiota-brain axis: Focus on gut steroids

There are over 1000 varieties of steroids that have been reported in nature, including the endogenous sex steroid hormones (i.e., progesterone, testosterone, and 17β-estradiol) and corticosteroids which are mainly synthesized by gonads and adrenals, respectively. In addition, an extra-glandular steroidogenesis has been also reported in the brain and in the gastrointestinal tract (GIT). The reason why intestinal steroidogenesis and consequently gut steroids draw our attention is for the communication and interaction with the gut microbiota, which functions like a virtual endocrine organ, and it is also involved in the steroid production. Moreover, both GIT and gut microbiota communicate through neural, endocrine, and humoral ways with the brain, in the so-called gut-microbiota-brain axis. On this basis, in this review, we will discuss several aspects such as (1) intestinal steroidogenesis and its possible regulation, (2) the potential role of gut steroids in physiopathological conditions, and (3) the role of microbiome in steroidogenesis and steroid metabolism. Overall, this review highlights new points of view considering steroid molecules as potential therapeutic approach for gastrointestinal disorders and brain comorbidities.