Work

Intestinal microbiota-associated LysoPC(16:0) promotes endometriosis via PPARγ-mediated M2 macrophage polarization and IL-10 secretion

Year: 2026

Type: article

Abstract: Both gut microbiota dysbiosis and altered pelvic immune microenvironment have been linked to endometriosis (EM), but the metabolites connecting the two remain undefined. Combining 16S rDNA sequencing with non-targeted metabolomics in a murine EM model, we found altered gut microbiota composition alongside a marked rise in peritoneal lysophosphatidylcholine (LysoPC(16:0)), linked to the microbiota shift by correlation analysis and fecal transplantation. LysoPC(16:0) promoted M2 macrophage polarization through peroxisome proliferator-activated receptor gamma (PPARγ), an effect observed in two mouse strains. Clodronate-mediated macrophage depletion blocked LysoPC(16:0)-driven lesion growth. LysoPC(16:0) further induced PPARγ-dependent IL-10 transcription, and IL-10 neutralization in vivo reduced lesion weight. Conditioned medium from LysoPC(16:0)-stimulated THP-1 macrophages promoted migration of primary endometrial stromal cells from patients with EM, an effect reversed by GW9662 or IL-10 neutralization. Together, these results outline a gut microbiota-LysoPC(16:0)-PPARγ-M2–IL-10 axis in EM pathogenesis, a mechanistic and therapeutic target for future clinical study.

Source: iScience

DOI: 10.1016/j.isci.2026.117917