Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

Abstract

Problem: Endometriosis (EMS) is a chronic inflammatory disease with unclear pathogenesis. Three studies have uncovered the influence of gut microbiota on mice with EMS, but no study has investigated the characteristics of fecal metabolomics to determine some important clues on EMS. This research aims to uncover the interaction between fecal metabolomics and gut microbiota in EMS mice. Method of study: Female C57BL/6J mice were used to construct the EMS model. Non-target metabolomics was applied to detect the fecal metabolites of EMS mice. The 16s rRNA sequencing was used for clarifying the composition of the gut microbiota. The functional characteristics of gut microbiota were analyzed using the PICRUSt. The receiver operator characteristic curve (ROC) analysis was utilized for determining the potential important differential metabolites, and the Spearman correlation coefficient was applied for expressing the correlation between the important differential metabolites and gut microbiota. Results: A total of 156 named differential metabolites were screened. The diversity and the abundance of gut microbiota in EMS mice decreased. Eleven pathways were involved in the differential metabolites and the functional prediction of gut microbiota, among which the second bile acid biosynthesis and alpha-linolenic acid (ALA) metabolism were the significant enrichment pathways. The increased abundance of chenodeoxycholic and ursodeoxycholic acids and the decreased abundance of ALA and 12,13-EOTrE were found in the feces of EMS mice. Conclusion: The abnormal fecal metabolites, which are influenced by dysbacteriosis, may be the characteristics of EMS mice and can be the potential important indices to distinguish the disease.

Associations Between Endometriosis and Gut Microbiota

“…Interestingly, antibiotic treatment to mice reduced the endometriosis lesions and inflammatory responses, changes which were restored after oral feces gavage [35]. Although different models were used to induce and evaluate endometriosis in mice, the results point to an association between endometriosis and gut microbiota and suggest that gut bacteria promote endometriotic lesion progression [31,[34][35][36]. However, the microbiota alterations may also depend on other functions, e.g., subclinical infections [37].…”

“…When endometriosis was induced in mice, a higher beta diversity of gut microbiota was developed first after 42 days, with similar alpha diversity, among the endometriosis mice compared with control mice [ 33 ]. In contrast, other mouse studies with endometriosis induction have described effects on the gut microbiota already after 21 days; one study found decreased diversity, richness, and abundance of gut microbiota [ 34 ] and one found increased alpha and beta diversity [ 35 ], whereas a third study could not identify any effect at all [ 36 ]. Interestingly, antibiotic treatment to mice reduced the endometriosis lesions and inflammatory responses, changes which were restored after oral feces gavage [ 35 ].…”

Metabolomics in endometriosis: challenges and perspectives for future studies

“…The other study using the homologous c57BL/6J mouse model is particularly distinctive from the rest of the studies reviewed since it correlates fecal metabolomics and gut microbiota in mice with endometriosis. Ni et al (2020) reported decreased diversity and richness of bacteria in an endometriosis group and significant differences in species composition between the disease group and control. In terms of metabolites, alpha-linoleic acid (ALA), chenodeoxycholic (CDCA), ursodeoxycholic acid (UDCA) and 12,11, contributed most to differences in fecal metabolome.…”

“…In terms of metabolites, alpha-linoleic acid (ALA), chenodeoxycholic (CDCA), ursodeoxycholic acid (UDCA) and 12,11, contributed most to differences in fecal metabolome. Ni et al (2020) suggest that CDCA, UDCA, and ALA have a protective role in the intestinal wall because of their anti-inflammatory effects (Paula et al 2018, Ko et al 2019, Song et al 2019, while 12,13-EOTrE may be related to inflammation and serve as a potential biomarker of endometriosis. Despite such findings, further studies are necessary to understand the correlation between endometriosis and these compounds (Ni et al 2020).…”

“…Dutta et al (2016) and Atkins et al (2019) have demonstrated significant differences between endometriosis and healthy controls and have reported important metabolites implicated in cell proliferation, cell survival, oxidative stress, altered mitochondrial function, high energy demand, and lipid dysregulation. On the other hand, Ni et al (2020) provided insight into understanding gastrointestinal symptoms commonly experienced by women with endometriosis. The study of the fecal metabolome in subjects with endometriosis is of relevance because it has been documented that women with endometriosis experience more abdominal pain, constipation, the urgency to defecate, bloating, and flatulence in comparison to healthy patients (Ek et al 2015).…”