Disrupted Tuzzerella abundance and impaired L-glutamine levels induce Treg accumulation in ovarian endometriosis: a comprehensive multi-omics analysis

Yichen Chen, Lingfang Ye, Jue Zhu, Liang Chen, Huan Chen, Yuhui Sun, Yishen Rong, Jing Zhang
Metabolomics : Official journal of the Metabolomic Society · 2024 · vol. 20(2) , pp. 32 · doi:10.1007/s11306-023-02072-0 · PMID:38424274 · PMC10904428 · W4392282091
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Reduced Tuzzerella abundance and lower L-glutamine levels in ovarian endometriosis were associated with increased C7 complement protein and subsequent accumulation of regulatory T cells.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This multi-omics study analyzed ovarian ectopic endometrium (OEMs) versus normal endometrium (NE) from women undergoing laparoscopic surgery, using 16S rRNA sequencing, LC–MS metabolomics, and proteomic profiling, with additional in vitro assays on ectopic and normal endometrial cells. The authors found significantly lower Tuzzerella abundance in OEMs and reported that endometriotic lesions were associated with decreased l-glutamine levels; proteomics identified upregulation of complement-related proteins (including C7), with analyses suggesting a negative regulation between l-glutamine and C7. In vitro experiments showed that high glutamine inhibited C7 expression, and tissue-based immune profiling associated higher C7 expression with greater regulatory T cell (Treg) infiltration while l-glutamine negatively regulated Treg chemotactic factors. A stated caveat is that the approach relies on correlation/linked multi-omics plus targeted validation rather than demonstrating causal mechanisms in vivo. This paper is centrally about endometriosis—linking disrupted Tuzzerella–l-glutamine–C7 immune regulation and Treg accumulation in ovarian endometriotic lesions.

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Female Female Female Female Female Female Female Female Female Glutamine

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