Mechanistic pathways of estrogen mitigating postmenopausal gut dysbiosis

Estrogen is classically considered an essential hormone signal and exerts profound effects on several physiological and pathological states, including gut health. Estrogen deficiency after menopause in most women leads to increased androgenicity and changes in body composition. It is recommended to manipulate the composition of gut bacteria, which alters gut integrity and hence leads to gut microbiota (GM) dysbiosis. Normally, the gut maintains its epithelial microvilli integrity with the help of intestinal barriers, such as tight junction (TJ) proteins (claudin, occludin, and epithelial cadherin), short-chain fatty acids (SCFAs) (acetic acid, propionic acid, isobutyric acid, formic acid, and butyric acid), and mucin. Estrogen influences the bacteria present in the gut. It appears to safeguard the integrity of the gut by inhibiting the breakdown of SCFAs, TJ proteins, and mucin. This protective mechanism serves to prevent the onset of dysbiosis. The estrobolome specialises in the processing of estrogen, playing a pivotal role in regulating estrogen metabolism within the gut. This imbalance is intricately linked to alterations in the estrobolome and endobolome, thereby influencing estrogen metabolism and availability. The estrogen deficiency and associated expressions of TJ proteins, SCFAs, and mucin advance the progression of postmenopausal-induced gynaecological disorders. However, the alterations in the composition and diversity of GM observed during menopause emphasize the pivotal role of estrogen in shaping the gut environment. Estrogen intricately regulates the estrobolome, TJ proteins, mucin, and SCFAs. Via this review, we have tried our best to enlighten on the detailed mechanisms showing the crosslink between estrogen and gut health.