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

The human body harbors at least as many microorganisms as own cells that \nsynergistically coexist and regulate several physiological functions supporting host life. \nMuch is known on how the gut microbiome influences human physiology and has a deep \ninfluence on human metabolism. These gut microbial communities are shaped by host \ngenetic and lifestyle factors, such as diet, physical activity or medications, among others. \nBecause an imbalance in the gut microbial communities (that is, dysbiosis) has been \nlinked to numerous pathological states, microbiome modulation by lifestyle factors \nemerges as a promising therapeutic strategy. Conversely, little is known about the \npresence and composition of the microbiome along the female reproductive tract and its \nrole in the development of gynecological diseases. Thus, despite of the strong correlation \nbetween the microbiome and human health and disease, there is still lack in characterizing \nand understanding the compositional and functional profiles of the host-associated \nmicrobes. \nThe present Doctoral Thesis examines the relationships of the microbiome with \nfemale health in association with physical activity and reproductive health performing \nmeta-omics analyses. Thus, the specific aims of this Doctoral Thesis were: 1) to \nsummarize and meta-analyze the state-of-the-art of the association of physical activity \nand sedentary behavior with the microbiome across different body sites in different \nhuman populations; 2) to study the associations between accelerometer-measured \nsedentary behavior and physical activity on different intensities (light and moderate-tovigorous) \nwith the gut microbiome using a compositional data analysis in middle-aged \nwomen; 3) to characterize the endometrial and Fallopian tubes’ microbial composition in \nfertile women in order to identify the female upper reproductive tract microbiome; 4) to \nprofile 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 \ndevelopment of the disease. To address the objectives of the Thesis, four studies were \nperformed, which were organized into two sections. Section I, Physical activity and \nmicrobial composition (Studies I and II); and section II: The microbiome in female \nreproductive health (Studies III and IV). \nThe main findings of this Doctoral Thesis were: 1) a systematic review of 91 \nstudies and meta-analyses uniting more than 2600 participants, where we gathered the \ncurrent knowledge of the association of physical activity and sedentary behavior with the \nmicrobiome. Most studies reported higher abundances of short-chain fatty acidsproducing \nmicrobes in more active individuals or after a physical activity intervention. \nWhile influence of physical activity on the microbial diversity is unclear, athletes seem \nto have a richer microbiome compared to non-athletes (Study I); 2) physical activity and \nsedentary behavior did not associate with the gut microbial diversity in the middle-aged \nwomen, however, several butyrate-producing microbes were significantly more abundant \nwhen increasing time of moderate-to-vigorous physical activity from light physical \nactivity/sedentary behaviors (Study II); 3) the endometrium and Fallopian tubes harbor \nan endogenous microbiome with high inter-individual variability, which share around \n70% of microbes and have specific bacteria of each anatomical site (Study III); 4) the \ngut microbiome profiles were not significantly different between the women with and \nwithout endometriosis, suggesting that the gut microbiome imbalance does not seem to \ndirectly impact the pathogenesis of the disease, nevertheless further research considering \nendometriosis severity stage and treatment strategies is warranted (Study IV).