Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis

• Published in: Journal of inflammation research 2024-07, Vol.17, p.4199-4217
• Main Authors: Li, Yangshuo, Zhou, Zhihao, Liang, Xiaolan, Ding, Jie, He, Yalun, Sun, Shuai, Cheng, Wen, Ni, Zhexin, Yu, Chaoqin
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; bile acids; Deoxycholic acid; Development and progression; Endometriosis; Estrogen; Ethylenediaminetetraacetic acid; gut microbiota; Health aspects; Information management; interleukin-17; Interleukins; Metronidazole; Microbiota (Symbiotic organisms); myeloid cell; Neomycin; Original Research; RNA; single-cell sequencing
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S458928

Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.