Gut, vaginal, and urinary microbiota as potential biomarkers of sensitization in women with chronic pelvic pain

Abstract

Background: A subgroup of patients with chronic pelvic pain exhibit organ sensitization of unknown origin and mechanism. Changes in microbiota composition in pelvic organs have been found to be associated with various pelvic pathologic conditions. Therefore, a comprehensive analysis of the gut and genitourinary microbiota composition and interactions in women with chronic pelvic pain may be key to understanding their involvement in the sensitization processes.

Objective: This study aimed to identify pelvic organ microbiota signatures that are associated with organ hypersensitivity in patients with chronic pelvic pain.

Study design: This study involved women with high (sensitized chronic pelvic pain, n=14) and low (nonsensitized chronic pelvic pain, n=14) pelvic sensitization scores according to the Convergences PP criteria. Pelvic organ sensitivity was assessed using a rectal barostat and noninvasive bladder, muscular, and vulvar sensory tests. Quality of life, pelvic symptoms, and psychological state were assessed. Using 16S ribosomal RNA gene sequencing, the gut, vaginal, and urinary microbiota diversity and composition were analyzed and compared between women with sensitized chronic pelvic pain and those with nonsensitized chronic pelvic pain. Differences in the abundant bacterial amplicon sequence variants between groups were associated with clinical characteristics and organ sensitivity. System biology approaches using weighted gene correlation network analysis were used to identify bacterial amplicon sequence variant modules associated with functional and clinical parameters.

Results: The pain pressure thresholds were considerably decreased in women with sensitized chronic pelvic pain in the vulva, rectum, bladder, and perineal muscles when compared with women with nonsensitized chronic pelvic pain. However, the pain intensity felt at the rectal, muscular, and bladder pain thresholds was markedly increased in women with sensitized chronic pelvic pain. After stimulation, women with sensitized chronic pelvic pain presented increased and prolonged pain in the perineal muscles and bladder when compared with women with nonsensitized chronic pelvic pain. The α- and β-diversities were substantially increased among women with sensitized chronic pelvic pain in the vaginal and urinary but not the gut microbiota. Using differential abundance analysis, we showed that 13 amplicon sequence variants in the gut, 6 in the vagina, and 2 in the bladder were differentially expressed between patients with sensitized chronic pelvic pain and those with nonsensitized chronic pelvic pain. More specifically, in the vaginal microbiota, a considerable increase in Streptococcus and Prevotella genera was observed in sensitized chronic pelvic pain when compared with nonsensitized chronic pelvic pain. A marked increase in Clostridium sensu stricto 1 amplicon sequence variants was observed in the urinary microbiota of patients with sensitized chronic pelvic pain when compared with those with nonsensitized chronic pelvic pain. Next, we found that 4 gut microbiota amplicon sequence variants (belonging to Akkermansia, Desulfovibrio, Faecalibacterium, and CAG-352) were correlated with pain intensity at the maximal rectal distension threshold. We also identified an amplicon sequence variant (Blautia) that was increased in nonsensitized chronic pelvic pain and that was inversely correlated to several gut sensitization markers. In the vaginal microbiota, the Lactobacillus jensenii amplicon sequence variants were associated with less dysmenorrhea and an increased bladder capacity. Furthermore, we identified 2 vaginal amplicon sequence variants belonging to Prevotella that were increased in sensitized chronic pelvic pain and associated with dysmenorrhea. Finally, using weighted gene correlation network analysis methods, we identified vaginal and urinary tract amplicon sequence variant modules driven by Peptostreptococcales-Tissierellales Peptoniphilus that were strongly correlated with rectal, muscular, and bladder poststimulation pain. We also identified a gut amplicon sequence variant module driven by Christensenellaceae_R-7 that was substantially associated with anxiety, gastrointestinal symptoms, and rectal sensitivity.

Conclusion: This work identified specific bacterial signatures of specific pelvic organs and their association with organ sensitization, which are potential therapeutic targets in chronic pelvic pain women.

Keywords: Convergences PP score; Lactobacillus; biomarker; chronic pelvic pain; microbiome; microbiota; sensitization.