Jiawei Qi Gong Wan Improves Endometrial Receptivity in PCOS-like Mice by Attenuating Inflammation: A Multi-Omics Study Linking Gut Microbiota and Metabolite Profiles.

Background/Objectives: Uterine dysfunction contributes to infertility in PCOS. Jiawei Qi Gong Wan (JQGW) is used to improve endometrial homeostasis, but its mechanism is unclear. This study investigated whether JQGW improves uterine function via gut microbiota and metabolites. Methods: Letrozole-induced PCOS mice received JQGW (low/high dose), metformin, or vehicle for 35 days. Endometrial morphology, receptivity genes, Akt2/NF-κB signaling, gut microbiota (16S rRNA), and serum metabolites (LC-MS) were assessed. Results: PCOS mice showed reduced endometrial thickness (126.4 ± 10.8 μm vs. 215.6 ± 12.3 μm in controls, p < 0.001) and fewer glands (12.6 ± 1.8 vs. 28.4 ± 2.1, p < 0.001). JQGW-H increased endometrial thickness (189.3 ± 11.2 μm, p < 0.01 vs. PCOS) and gland number (23.1 ± 1.9, p < 0.01 vs. PCOS), restored the receptivity markers (Nr2f2, Pc6, Ptch, and Hbegf) toward normal levels, suppressed Akt2/NF-κB activation, and reduced inflammatory cytokines. JQGW shifted the β-diversity structure of the gut microbiota toward the control pattern, with Oscillospira enrichment (LDA > 4). Four metabolites (PA(20:0/16:1(9Z)), 7-methylguanosine, methoxyacetic acid, 8.11-eicosadiynoic acid) showed nominal elevation in PCOS and negative correlations with endometrial thickness (r = -0.73 to -0.89, unadjusted p < 0.01), although none survived FDR correction. Conclusions: JQGW ameliorates PCOS-associated uterine dysfunction, potentially via gut microbiota and metabolite modulation. Future studies should validate causality using fertility-based outcomes and microbiota transplantation.