Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Abstract

Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to characterize the sex differences in gut microbiota, and to explore the impact of depletion of gonadal hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbiota, as consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbiota, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk.

Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation

“…Furthermore, studies have shown a stronger impact of female gonadal hormones on GM. A study in rats showed that while the sex-dependent differences in GM community persisted after gonadectomy, the detrimental impact was more pronounced in female rats, especially when animals were overfed (Santos-Marcos et al, 2020). This is indeed in line with observations in humans demonstrating a shift in the GM profile in post-menopausal women compared to age matched men (Santos-Marcos et al, 2018).…”

“…Along the same lines, the strong associations observed between sex and -diversity in young adults, though persisted after adjusting for cardiometabolic parameters, tended to diminish after 40 years of age (de la Cuesta-Zuluaga et al, 2019) consistent with an age-related decline in the level of sex hormones. Importantly, the interaction between GM and female sex hormones appear to be bidirectional whereby a study on rats showed that several GM-derived microRNAs were reported to modulate steroid biosynthesis and estrogen signaling (Santos-Marcos et al, 2020). While less clear in human studies, accumulating evidence from experiments on mice suggests that the differential diversity in GM can drive sexually dimorphic immune responses (Elderman et al, 2018;Felix et al, 2018).…”

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

“…Similarly, Dorea was positively associated with physical activity. In support of these findings, ovariectomy increases weight gain in both STND- and HFD-fed rats and is associated with changes in gut microbiota [ 59 ]. Similarly, in a PCOS mouse model, FMT from androgen-treated mice disrupts metabolic and endocrine health in germ-free recipients, whereas gut microbiota from control donors protects against metabolic dysregulation [ 60 , 61 , 62 ].…”

Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

“…In addition, the way in which pollutants interfere with gonadal hormones in shaping the gut microbiota would as well be interesting to determine. Indeed, gut microbiota exhibits sexual differences probably originating from complex interactions between sex and nutrition [ 216 ].…”