High-Fat Diets Promote Peritoneal Inflammation and Aggravate Endometriosis-Associated Pain in a Mouse Model of Endometriosis

Endometriosis is a chronic inflammatory disease with a complex symptomatic and pathobiological nature that affects about 10% of reproductive-aged women. It is a condition with a complex array of causes and disease phenotypes and is characterized by the presence of endometrial tissues growing outside of the uterus. While symptom severity may differ from patient to patient, common disease phenotypes include chronic pelvic pain, dyspareunia (painful intercourse), dysmenorrhea (painful periods), dysuria (painful urination), fatigue, and infertility. While there are a variety of risk factors for developing endometriosis, the effects of western, high-fat diets (HFD) are a growing concern, especially in the development of more severe symptoms. Typical high-fat western diets have been linked to greater systemic inflammation and dysmenorrhea, which makes it necessary to know how the altered physiology caused by HFD affects the severity of endometriosis symptoms. To study the effects of HFD on endometriosis, we used an innovative endometriosis mouse model that has been developed in Hayashi Lab to characterize whether HFD influence endometriosis-associated symptoms such as hyperalgesia (pain). Since both obesity and endometriosis are chronic inflammatory conditions, a comprehensive study of immune cells profiles in the peritoneal cavity, lesions, related inflammatory factors, and dorsal root ganglia (DRG) to assess alterations of peripheral nerves, was designed to provide necessary insight into the interplay of these diseases. We sought to examine how HFDs alter systemic and local immune environments in endometriosis and discern their contribution to endometriotic-associated hyperalgesia

Urban Impacts on Surface Water Microbiome in the Lower Portneuf River Valley Watershed

Rapid urbanization within the last several decades has affected the Earth’s biosphere, including microbial ecosystems. One example is the release of various pollutants, both abiotic and biotic, into the aquatic environment by urban stormwater runoff. Common abiotic pollutants include elevated nutrient loads from domestic wastewater effluent and/or septic tank leaking, drug compounds from antimicrobial medication use, and pharmaceuticals and personal care products (PPCPs); they represent an ecological driving force on the micro-biosphere. Common biotic pollutants include microbiota associated with humans and their pets as well as genetic material of those microorganisms. Together, these abiotic and biotic pollutants could have profound impacts on microbial communities in the aquatic environment. Specifically, the increasing presence of antimicrobial compounds and other PPCPs may promote genomic augmentation within microbial communities residing in hotspots that leads to a decrease in microbial susceptibility to antibiotics. This study aims to use the lower Portneuf River valley watershed as a natural laboratory to examine impacts of the City of Pocatello, Idaho on surface water microbial communities. Water samples were collected along an urban impact gradient across the Pocatello Creek watershed, a tributary of the Portneuf River. Total environmental DNA was extracted from 20 surface water samples. Metagenomic analysis was conducted on bacterial 16S rRNA genes for profiling microbial community structure and predicting community function. Conventional PCR was performed to identify the presence of 19 antibiotic resistance genes, 3 different mobile genetic elements, and 2 biomarkers indicating human and dog specific fecal pollution. Real-time PCR was conducted to quantitatively assess the occurrence of selected resistance genes, nitrogen cycling related microbial groups, and the dog fecal pollution biomarker. These nested microbiome analyses, in conjunction with water chemistry data, offered a better understanding of urban impacts on surface water microbiome, water quality, and potential public health issues at the watershed level

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

DataSheet_1_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.docx

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.</p

Image_3_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.jpg

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.</p

Table_1_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.docx

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.</p

Image_1_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.jpg

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.</p

DataSheet_2_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.docx

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.</p

Image_2_High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.jpg

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.</p