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Disrupted Tuzzerella abundance and impaired l-glutamine levels induce Treg accumulation in ovarian endometriosis: a comprehensive multi-omics analysis.
- Source :
-
Metabolomics . Apr2024, Vol. 20 Issue 2, p1-14. 14p. - Publication Year :
- 2024
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Abstract
- Introduction: The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited. Methods: All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis. Results: We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in l-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between l-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while l-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs. Conclusion: In this study, we found a clear multi-omics pathway alteration, "Tuzzerella (microbe)—l-Glutamine (metabolite)—C7 (protein)," which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15733882
- Volume :
- 20
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Metabolomics
- Publication Type :
- Academic Journal
- Accession number :
- 176300742
- Full Text :
- https://doi.org/10.1007/s11306-023-02072-0