Herup-Wheeler Tristin, Shi Mingxin, Harvey Madeleine E, Talwar Chandni, Kommagani Ramakrishna, MacLean James A, Hayashi Kanako
School of Molecular Bioscience, Center for Reproductive Biology, Washington State University, Pullman, WA 99614, USA.
Department of Pathology & Immunology, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
bioRxiv. 2023 Nov 13:2023.11.09.566474. doi: 10.1101/2023.11.09.566474.
Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD alter an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal mechanical allodynia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure to HFD. Pain-related mediators in the dorsal root ganglia were further stimulated after lesion induction under the HFD condition. Although HFD did not affect inflammatory macrophages in the peritoneal cavity without lesion induction, the diversity and composition of the gut microbiota were clearly altered by HFD as a sign of low-grade systemic inflammation. Thus, HFD alone might not establish a local inflammatory environment in the pelvic cavity, but it can contribute to further enhancing chronic inflammation, leading to the exacerbation of endometriosis-associated abdominal hyperalgesia following the establishment and progression of the disease.
免疫功能障碍是通过建立慢性炎症环境在子宫内膜异位症发生和发展过程中的核心组成部分之一。西式高脂饮食（HFD）与更严重的全身炎症相关，可导致代谢和慢性炎症性疾病，也被认为是妇科疾病的一个环境风险因素。在此，我们旨在研究高脂饮食如何改变子宫内膜异位症中的炎症环境，并确定它们对子宫内膜异位症相关痛觉过敏的影响。我们的结果表明，高脂饮食诱导的肥胖增强了由子宫内膜异位症病变引起的腹部机械性异常性疼痛。慢性暴露于高脂饮食会使因病变诱导而增加的腹膜炎性巨噬细胞和细胞因子水平进一步升高。在高脂饮食条件下，病变诱导后背根神经节中与疼痛相关的介质会受到进一步刺激。虽然在没有病变诱导的情况下，高脂饮食不会影响腹腔内的炎性巨噬细胞，但高脂饮食会明显改变肠道微生物群的多样性和组成，这是低度全身炎症的一个迹象。因此，单纯的高脂饮食可能不会在盆腔内建立局部炎症环境，但它会促使慢性炎症进一步加重，导致在疾病建立和进展后子宫内膜异位症相关的腹部痛觉过敏加剧。
