Effects of endometriosis on immunity and mucosal microbial community dynamics in female olive baboons

Abstract

Endometriosis is defined as the growth of endometrial tissue in ectopic locations, and is associated with altered immune and microbial phenotypes. It is unclear if these changes are the result of the disease or may be causative. We induced endometriosis in non-human primates (Papio Anubis) to test our hypothesis that the growth of endometriotic lesions results in alterations in immune and microbial dynamics that may advance disease progression. Baboon samples were collected pre-inoculation (prior to disease induction), at 3, 6, 9, and 15 months after disease induction. Tolerant regulatory T-cells (Tregs) and inflammatory T-helper 17 (Th17) cells were identified in peripheral blood and within the eutopic/ectopic endometrial tissues. Microbiome communities were identified in fecal/urine samples. The induction of endometriosis decreased peripheral Tregs cells while Th17 cells increased at all post-induction collections, thus reducing the Tregs:Th17 cells ratio, indicating systemic inflammation. Microbiome diversity and abundance were altered at each sample site after disease induction. Thus, induction of endometriosis in baboons caused an immune shift toward an inflammatory profile and altered mucosal microbial profiles, which may drive inflammation through production of inflammatory mediators. Immune and microbial profiling may lead to innovative diagnostic tools and novel therapies for endometriosis treatment.

Role of the gut microbiota in the pathogenesis of endometriosis: a review

“…Le et al detected that microbiome diversity and abundance were altered at each baboon induced of endometriosis. The induction of endometriosis decreased peripheral Tregs cells while Th17 cells increased at all post-induction collections that caused an immune shift toward an inflammatory profile and altered mucosal microbial profiles ( Le et al, 2022 ). More and more evidences suggest that the abnormal quantity and activity of Treg cells can lead to dysregulation of the immune microenvironment in the body, decreased pelvic immune function, and immune escape, thereby promoting the implantation and growth of ectopic endometrium outside the uterus.…”

Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review

“…The majority of the clinical studies investigating endometriosis and microbiome changes were derived from Asia including Japan, China, Taiwan, Korea, and Turkey ( Table 3 , Supplementary Table S1 ) [ 21 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ]. There were also some studies from the United States, Brazil, Sweden, and Canada [ 119 , 120 , 121 , 122 , 123 ]. Almost all the clinical trials conducted diagnosed endometriosis cases via laparoscopy or histology tests and scored based on the criteria described in the Revised American Society for Reproductive Medicine (r-ASRM) classification of endometriosis.…”

“…Another recent study on non-human primates, olive baboons ( Papio Anubis ) in reproductive age also indicated the involvement of T regulatory cells as they investigated changes in the gastrointestinal and urogenital microbiome [ 121 ]. Similar to findings from the rodents’ model of endometriosis, the team reported dynamic changes in the gut microbiome of these olive baboons throughout their 15-months study.…”

“…Another essential point to consider in the crosstalk of microbiome and host processes is the estrogen-microbiome axis [ 121 , 124 , 153 , 154 , 155 ]. While studies have noted the relationship between the microbiome and immune response, emerging data is reflecting that alterations in the estrobolome brought upon by dysbiosis can trigger estrogen-mediated pathologies, including endometriosis as well as endometrial cancer.…”

Targeting Oxidative Stress Involved in Endometriosis and Its Pain

“…Studies have examined the gut microbiota in relation to the development and treatment of endometriosis [ 164 , 165 ]. Though, Hantschel et al [ 166 , 167 ] did not find significant changes in gut microbiota in endometriotic mice 21 days after inoculation, other studies in baboons [ 168 ] or mice [ 169 ] have found that inoculation with endometriosis significantly changed the abundance and diversity of the gut microbiome after 45–90 days, resulting in dysbiosis. The association between gut microbiota and endometriosis was further elucidated in a study by Chadchan et al, who found that oral antibiotics reduced endometriosis progression in mice [ 170 ].…”