Parabacteroides goldsteinii and its metabolite 7-KLCA attenuate endometriosis via TGR5 to reprogram macrophages by modulating the PPARγ/GPR132 axis

  • NPJ Biofilms Microbiomes. 2026 May 22. doi: 10.1038/s41522-026-01017-4.
Yun Chen  1  2 ,  Yuqing Qiu  1 ,  Feifei Pan  1  2 ,  Yanqin Zheng  1 ,  Jingyao Wang  1  2 ,  Kunxiang Gong  1  2 ,  Lirong Guo  1  2 ,  Yiming Song  1 ,  Zixin Tao  3 ,  Kun Shi  4
Affiliations
  • 1. Department of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 2. Institute of Reproductive Health and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 3. Department of Gynecology and Obstetrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China. [email protected].
  • 4. Department of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. [email protected].
PMID: 42173876 DOI: 10.1038/s41522-026-01017-4
Abstract

Endometriosis (EMS) remains understudied in effective management strategies. The interplay between macrophage dysfunction and microbiota-derived immune signals emerges as a potential mechanism in EMS pathogenesis, suggesting its relevance for future therapeutic exploration. In this study, we established mouse models to demonstrate that gut microbiota modulated EMS development. Integrated microbial and metabolomic profiling identified Parabacteroides goldsteinii (Pg) as a promising probiotic candidate, whose downstream metabolite 7-ketolithocholic acid (7-KLCA) exhibiting therapeutic efficacy in ameliorating EMS phenotypes upon supplementation. Mechanistically, Pg reshapes its bile acid (BA) metabolism to elevate 7-KLCA. This bioactive metabolite acts via the receptor TGR5 to suppress PPARγ expression and activate GPR132, thereby enhancing efferocytosis and promoting M1 macrophage polarization. These findings uncover a gut-metabolite-immune regulatory axis through which Pg reprograms macrophage function to restrain EMS progression, offering a potential microbial perspective for this chronic condition.

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