Progesterone supplementation in mice leads to microbiome alterations and weight gain in a sex-specific manner

Abstract

BackgroundProgesterone is a steroid hormone produced by the ovaries, involved in pregnancy progression and necessary for successful gestation. We have previously shown that progesterone affects gut microbiota composition and leads to increased relative abundance of Bifidobacterium.ResultsIn non-pregnant female GF mice, levels of progesterone were significantly higher than in SPF mice of the same status. However, no significant differences were observed between GF and SPF males. Females treated with progesterone gained more weight than females treated with a placebo. In contrast to female mice, males treated with progesterone did not gain significantly more weight than males treated with a placebo. Progesterone supplementation led to microbial changes in females but not in males (16S rRNA sequencing). Accordingly, the weight gain observed in female mice treated with progesterone was fully transferable to both male and female germ-free mice via fecal transplantation.ConclusionsWe demonstrate that bacteria play a role in regulating progesterone levels in a female-specific manner. Furthermore, weight gain and metabolic changes associated with progesterone may be mediated by the gut microbiota.

Intestinal flora and pregnancy complications: Current insights and future prospects

“…This is further supported by evidence showing that administering progesterone to women with a history of PTBs and a high risk of recurrence can decrease the likelihood of another PTB by 33% [ 54 ]. Another research conducted by Nuriel‐Ohayon et al revealed that administering progesterone alters the gut microbiome in females, resulting in weight gain, an effect replicable in germ‐free mice through fecal transplant [ 55 ]. These findings illustrate a complex interaction between gut microbiota and progesterone.…”