Gut microbiota metabolic axis dysfunction in estrogen deficient stressed rats.

Abstract

Gut dysbiosis, an imbalance in the gut microbiota (GM), has emerged as a key factor contributing to metabolic dysfunction following estrogen deficiency in menopause. Disruptions in gut microbial composition, triggered by hormonal imbalances and chronic stress, can exacerbate metabolic disturbances, such as obesity, dyslipidemia, and diabetes etc. Thus strategies, which modulates gut dysbiosis may proves important for the treatment of metabolic dysfunctions in postmenopausal state. However, the physiological, biochemical and molecular changes occurring due to estrogen deficiency and stress are yet to be elucidated. Thus, aim of the present study was to develop a pre-clinical model to investigate the effect of estrogen deficiency and chronic unpredictable mild stress (CUMS) alone and in combination on GM alterations and associated metabolic dysfunction. Ovariectomized (OVX) rats were subjected to CUMS for 28 days to induce metabolic alterations and gut dysbiosis. Estrogen deficiency and chronic stress altered physiological changes, adiposity, and anthropometric markers. Furthermore, OVX and CUMS elevated oxidative stress in liver and colon and increased inflammatory markers as detected in serum, Liver, and colon. This, in turn, led to damage of the mucosal layer and disruption of tight junction proteins. OVX and CUMS also caused gut dysbiosis, as indicated by an increased ratio of pathogenic to beneficial gut bacterial populations. Histopathological examination showed colon and liver tissues damage in OVX, CUMS, and OVX + CUMS group rats. OVX and CUMS, both individually and synergistically, contributed to the development of gut and metabolic dysfunction, collectively referred to as gut-metabolic axis dysfunction in OVX-stressed rats.