Microbiome in women: a focus on physical activity and reproductive health

Resum

The human body harbors at least as many microorganisms as own cells that synergistically coexist and regulate several physiological functions supporting host life. Much is known on how the gut microbiome influences human physiology and has a deep influence on human metabolism. These gut microbial communities are shaped by host genetic and lifestyle factors, such as diet, physical activity or medications, among others. Because an imbalance in the gut microbial communities (that is, dysbiosis) has been linked to numerous pathological states, microbiome modulation by lifestyle factors emerges as a promising therapeutic strategy. Conversely, little is known about the presence and composition of the microbiome along the female reproductive tract and its role in the development of gynecological diseases. Thus, despite of the strong correlation between the microbiome and human health and disease, there is still lack in characterizing and understanding the compositional and functional profiles of the host-associated microbes. The present Doctoral Thesis examines the relationships of the microbiome with female health in association with physical activity and reproductive health performing meta-omics analyses. Thus, the specific aims of this Doctoral Thesis were: 1) to summarize and meta-analyze the state-of-the-art of the association of physical activity and sedentary behavior with the microbiome across different body sites in different human populations; 2) to study the associations between accelerometer-measured sedentary behavior and physical activity on different intensities (light and moderate-tovigorous) with the gut microbiome using a compositional data analysis in middle-aged women; 3) to characterize the endometrial and Fallopian tubes’ microbial composition in fertile women in order to identify the female upper reproductive tract microbiome; 4) to profile and compare the gut microbiome in women with and without endometriosis in a large cohort in order to identify microbes and microbial pathways associated with the development of the disease. To address the objectives of the Thesis, four studies were performed, which were organized into two sections. Section I, Physical activity and microbial composition (Studies I and II); and section II: The microbiome in female reproductive health (Studies III and IV). The main findings of this Doctoral Thesis were: 1) a systematic review of 91 studies and meta-analyses uniting more than 2600 participants, where we gathered the current knowledge of the association of physical activity and sedentary behavior with the microbiome. Most studies reported higher abundances of short-chain fatty acidsproducing microbes in more active individuals or after a physical activity intervention. While influence of physical activity on the microbial diversity is unclear, athletes seem to have a richer microbiome compared to non-athletes (Study I); 2) physical activity and sedentary behavior did not associate with the gut microbial diversity in the middle-aged women, however, several butyrate-producing microbes were significantly more abundant when increasing time of moderate-to-vigorous physical activity from light physical activity/sedentary behaviors (Study II); 3) the endometrium and Fallopian tubes harbor an endogenous microbiome with high inter-individual variability, which share around 70% of microbes and have specific bacteria of each anatomical site (Study III); 4) the gut microbiome profiles were not significantly different between the women with and without endometriosis, suggesting that the gut microbiome imbalance does not seem to directly impact the pathogenesis of the disease, nevertheless further research considering endometriosis severity stage and treatment strategies is warranted (Study IV).