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.
Highlights
Aging is the largest risk factor for cardiovascular diseases (CVD) [1]
We found a higher α-diversity of the bacterial community in gonadal-intact females than in males, as assessed by both Shannon and Observed OTUs indexes under normal feeding (NL-control diet (CD)) or postnatal overfeeding (SLHFD) conditions (Supplementary Figure 1A)
In terms of bacterial composition, normal feeding condition (NL-CD) males were characterized by higher Elusimicrobia, Cyanobacteria, and Verrucomicrobia phyla, whereas females were characterized by higher Euryarchaeota and TM7 phyla
Summary
Aging is the largest risk factor for cardiovascular diseases (CVD) [1]. coronary heart disease usually starts in women 10 years later than in men, a difference that increases to 20 years for cardiac events such as myocardial infarction [2, 3]. The gut microbiota has been shown to be involved in the development of CVD [7], suggesting a potential role in the dimorphism of their incidence, as gender, in addition to other factors, such as age, genetic make-up and nutritional habits, impacts on gut microbiota architecture [8,9,10]. In recent years there has been accumulating evidence suggesting that the differences in the intestinal microbiota according to gender may be associated with the sex differences observed in the development of autoimmune, metabolic and CV diseases [11, 12]. The composition of the intestinal microbiota depends on the interactions between diet and the host’s gender, and the therapies used to restore the dysbiosis of the gut microbiota associated to disease should be gender-specific
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