Clostridium innocuum, an opportunistic gut pathogen, inactivates host gut progesterone and arrests ovarian follicular development
Journal
Gut microbes
Journal Volume
16
Journal Issue
1
ISSN
1949-0984
Date Issued
2024-11-07
Author(s)
Chou, Chia-Hung
Hsiao, Tsun-Hsien
Wu, Tien-Yu
Li, Chi-Ying
Gicana, Ronnie G
Shih, Chao-Jen
Brandon-Mong, Guo-Jie
Lai, Yi-Li
Li, Po-Ting
Tseng, Yu-Lin
Wang, Po-Hsiang
Chiang, Yin-Ru
Abstract
Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. Our data indicated as a major species involved in gut progesterone metabolism in women with infertility. converts progesterone into the neurosteroid epipregnanolone (with negligible progestogenic activity). We purified and characterized the corresponding enzyme, namely NADPH-dependent 5β-dihydroprogesterone reductase, which is highly oxygen sensitive and whose corresponding genes are prevalent in . Moreover, -administered female C57BL/6 mice (aged 7 weeks) exhibited decreased plasma progesterone levels (~35%). -specific antibiotics (metronidazole) restored low plasma progesterone levels in these mice. Furthermore, prolonged administration (12 weeks) arrested ovarian follicular development in female mice. Cytological and histological analyses indicated that may cause luteal phase insufficiency and affect menstrual regularity. Our findings suggest as a causal factor of progesterone resistance in women taking progesterone.
Subjects
Clostridium innocuum
epipregnanolone
gut microbiome
infertility
low progesterone bioavailability
mouse
neurosteroid
oral progesterone supplement
progesterone
SDGs
Description
Article number 2424911
Type
journal article