Bidirectional Communication of Estrogen in Gut-Brain Axis: Evidence from Preclinical and Clinical Studies

Estrogen deficiency in postmenopausal women influences several physiological processes, notably affecting the gut-brain axis (GBA). Emerging evidence from both preclinical and clinical studies suggests that the loss of estrogen following menopause contributes to GBA dysfunction. The present review aims to explore the clinical and preclinical evidence linking estrogen deficiency-induced gut dysbiosis with GBA dysfunction in postmenopausal women.

A literature survey was conducted using scientific databases such as PubMed, Google Scholar, ResearchGate, and Semantic Scholar to evaluate studies focused on estrogen's role in modulating GBA dysfunction using keywords such as estrogen, GBA, menopause, gut dysbiosis, and GM. Both experimental and observational studies were considered to synthesize current findings.

Estrogen deficiency has been shown to alter the composition and diversity of GM, impair gut barrier function, and dysregulate immune responses involving T cells and microglia within the GIT and CNS. These disruptions are associated with cognitive decline, emotional disturbances, and neurodegenerative conditions. Evidence supports a strong association between menopause-related estrogen loss, gut microbial imbalance, and GBA dysfunction.

The estrogen-GBA plays a crucial role in postmenopausal health, and phytoestrogenmediated modulation of GM offers a promising therapeutic approach supported by preclinical evidence. However, limited clinical data and population variability highlight the need for well-designed human studies to validate these findings.

Targeting GM modulation presents a promising therapeutic strategy for mitigating GBA dysfunction in postmenopausal women. This review consolidates existing evidence and highlights the need for further research into microbiota-based interventions to alleviate estrogen deficiency- related neurophysiological disorders.