Gut Microbiome Structure and Metabolic Analysis in the Obese PCOS Patients After The Treatment of Exenatide Combined with Metformin and Metformin Only

Emerging evidence has linked the gut microbiome to obese/overweight PCOS patients. Since GLP-1Ras and/or exenatide could alleviate the phenotype of PCOS patients, we tend to identify their differences in the mechanism through a metagenome-wide association study and serum metabolomics profiling in a cohort of obese/overweight PCOS women. Obese patients with PCOS were distributed to two groups: one received exenatide combined with metformin (COM group, n=28) and the other used metformin alone (MF group, n=22) received metabolomic profiling. Fresh fecal specimens from the participants, including 29 PCOS patients and 6 healthy controls, were collected for metagenome analysis. In the Post_MF group, the enrichment of M58_7XD, AM30_15AC and AF42_9BH of R. gnavus were negatively correlated with 3b,16a-Di-hydroxyandrostenone sulfate (3b,16a-DHEAS) and 8,11,14-Nonadecatriynoic acid. Dorea longicatena in the MF_Post group and is positively correlated with 10-hydroxy-2E-decenoic id (10HDA). Interestingly, Mega-mona funiformis, Clostridium sp CAG _226, Firmicutes bacterium CAG_341, Pseudoflavonifractor sp MSJ 30, unclassified g Turicibacter in the COM group were positively associated with 3b,16a-DHEAS and 8,11,14-Non-adecatriynoic acid. Besides, Megamonas_funiformis was negatively correlated with Coriandrone B and Clos-tridium_sp_CAG_226, Firmicutebacterium_CAG_341 and Pseudoflavonifractor_sp_MSJ_30 were positively associated with the increase of 1alpha,21-dihydroxy-20-oxo-22,23,24,25,26,27-hexanorvitamin D3. Exenati-de combined with metformin increased the abundance of M. funiformis, Clostridium_sp, Firmicutes_bacterium Pseudoflavonifractor_sp and reduce certain Ruminococcus_spp better than the impact of metformin on the gut flora of obese PCOS patients and these changes were associated with the reduction of the derivatives of DHEA and 8,11,14-Nonadecatriynoic acid, resultantly alleviating PCOS-like phenotype like hyperandrogenemia and insulin resistance. In the MF group, the enrichment of Dorea longicatena was related to the production of 10HDA to improve the clinical phenotype of PCOS.