High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.

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 cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure to HFD. Increased expression of pain-related mediators in the dorsal root ganglia was observed 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.

High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.

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.

The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness.

Oxidative damage to DNA is a significant source of mutations in living organisms. While DNA damage must be repaired to maintain the integrity of the genome and cell survival, errors made during DNA repair may contribute to evolution. Previous work has revealed that Campylobacter jejuni growth in the presence of bile salt deoxycholate (DOC) causes an increase in reactive oxygen species and the occurrence of 8-oxo-deoxyguanosine (8-oxo-dG) DNA lesions. The fundamental goal of this project was to determine if C. jejuni growth in a medium containing DOC contributes to DNA mutations that provide a fitness advantage to the bacterium. Co-culture experiments revealed that C. jejuni growth in a DOC-supplemented medium increases the total number of ciprofloxacin-resistant isolates compared to C. jejuni grown in the absence of DOC. We recovered two individual isolates grown in a medium with DOC that had a point mutation in the gene encoding the EptC phosphoethanolamine transferase. Transformants harboring the EptC variant protein showed enhanced resistance to the antimicrobial agent polymyxin B and DOC when compared to an eptC deletion mutant or the isolate complemented with a wild-type copy of the gene. Finally, we found that the base excision repair (BER), homologous recombination repair (HRR), and nucleotide excision repair (NER) are involved in general oxidative damage repair in C. jejuni but that the BER pathway plays the primary role in the repair of the 8-oxo-dG lesion. We postulate that bile salts drive C. jejuni mutations (adaptations) and enhance bacterial fitness in animals.