Exploring the Interconnection Between Endometriosis, Anxiety, and the Vaginal and Rectal Microbiome at Time of Surgery

INTRODUCTION: Endometriosis is a multifaceted gynecological disease that affects 10–15% of individuals assigned female at birth. Laparoscopic excision can assist with the removal of endometrial-like tissue and in treatment of infertility and pain. However, alleviation of other co-occurring symptoms, such as anxiety, is not well understood. Research suggests that alterations in the vaginal and rectal microbiome may play a key role in the development of endometriosis and co-occurring anxiety. OBJECTIVE: The primary purpose of this study is to identify microbial composition alterations among patients undergoing gynecological laparoscopies and diagnosed with endometriosis compared to patients without endometriosis. Further, exploratory analysis will evaluate microbial composition alterations among patients self-reporting moderate to severe anxiety symptoms compared to those with minimal or no anxiety symptoms. METHODS: A pilot study was conducted using convenience sampling with 80 individuals, 42 diagnosed with endometriosis and 38 with no endometriosis, undergoing laparoscopic gynecological procedures performed by minimally invasive gynecological surgeons at an urban tertiary care center in Phoenix. Validated Patient-Reported Outcomes Measurement Information System, Generalized Anxiety Disorder-7, and Endometriosis Health Profile surveys were collected to assess mental health and anxiety symptoms. 16S rRNA microbial sequencing was performed to determine vaginal and rectal microbial signatures utilizing MicrobiomeAnalyst and R software. RESULTS: Patients diagnosed with endometriosis were younger in age (mean age, 33 vs 42; P<0.0001), had a higher education level (P=0.03), lower BMI (mean BMI, 28.9 vs 33.8, P=0.01), higher prevalence of chronic pelvic pain (P=0.01), self-reported diagnosis and/or treatment for anxiety (P=0.04), and lower vaginal pH (P=0.03) compared to patients without endometriosis. The vaginal microbiomes in individuals with endometriosis exhibited increased species evenness (P=0.02) with an increase in the abundance of Lactobacillus species (P=0.01) and Aerococcus (P=0.002). The rectal microbiome indicated higher abundance of bacteria associated with estrogen metabolism (q<0.0001) in patients with endometriosis. The vaginal microbiome was not altered in patients with higher levels of anxiety as measured by GAD-7. However, we identified in patients with high levels of anxiety a decrease in rectal genus richness (P=0.04), and an increase in the abundance of Alloscardovia (q=0.005), a known estrogen metabolizer. Putative metabolic pathway analysis identified rectal pathways related to steroid degradation (p=0.04) and vaginal pathways related to sphingolipid (p=0.03) and secondary bile acid biosynthesis (p=0.04) elevated in patients with endometriosis. In contrast, patients with higher anxiety levels had rectal pathways elevated in isoflavonoid biosynthesis (q=0.0001) and vaginal pathways elevated in terpenoid metabolism (q<0.0001). CONCLUSIONS: Taken together, we identified differential microbial signatures associated with patients diagnosed with endometriosis and/or anxiety, providing insights into the microbial role in symptoms that co-occur with endometriosis and opening avenues for further research into areas targeting microbial-mediated estrogen and bile acid metabolism. Understanding the roles of the microbiome could lead to more personalized treatment plans tailored to individual patients' specific symptom profiles and biological factors, such as the estrobolome, curating a holistic approach integrated with surgical interventions.