Distinct Gastrointestinal and Reproductive Microbial Patterns in Female Holobiont of Infertility

Abstract

The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT–GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of ‘female holobiont’ as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman’s health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects.