Effect Of Metformin On The Intestinal Flora Of Obese PCOS

ObjectiveTo explore the effects of metformin on the gut microbiome of obese PCOS patient.MethodsFrom May 2019 to September 2019,30 obese PCOS patients who fulfilled the inclusion criteria in our hospital were selected as the obese PCOS patient group and 15 female patients who fulfilled the inclusion criteria due to male factors or fallopian tube factors were selected as the control group.Obese PCOS patients were randomly divided into two groups according to the order of outpatient visits,one group was only given Diane 35 while another group was given Diane 35 combined with metformin for 3 cycles,and the control group was not treated.We compared and analyzed the general data,sex hormones,blood lipids,blood sugar and insulin levels of the three groups of patients before and after treatment,at the same time we collected fresh feces before and after treatment in the control group,Diane 35 group and combination medication group then,the fecal DNA of all the groups were extracted.The V3-V4 region of the bacterial 16SrDNA was amplified,and high-throughput sequencing was performed on the Illumina HiSeq 2500 sequencing platform to analyze changes in the intestinal flora of the two groups of patients before and after treatment.The results of gut microbiome sequencing were analyzed on the BMK cloud platform,and the clinical data were analyzed by using SPSS21.0.Result 1.Clinical indicators: The BMI,LH,LH / FSH and T of the obese PCOS group before treatment were significantly higher than those of the control group.The age and FSH were not significantly different between the two groups.After treatment,the BMI,LH,LH / FSH,T,FPG,FINS,TC,TG,LDLC,and HOMA-IR of the Diane 35 group and the combined medication group significantly decreased and were lower than that of control group,and the HDLC level significantly increased and was higher than that of control group.Compared with the Diane 35 groups after treatment,BMI,LH,LH / FSH,T,FPG,FINS,TC,TG,LDLC and HOMA-IR of the combined medication group were significantly reduced(P <0.05),and HDLC was significantly increased(P <0.05).2.Sequencing results of gut microbiomeDiversity: There was no significant difference in the Chao1 index,ACE index,Shannon index,Simpson index of gut microbiome between obese PCOS patients,control group or obese PCOS patients before and after treatment.Through principal component analysis(PCA)and non-metric multidimensional scaling(NMDS)analysis,we found that the intestinal flora of obese PCOS patients was significantly different from that of the control group.Metformin could significantly change the intestinal microflora β diversity of obese PCOS patients before and after treatment.Species composition analysis: At the phylum level,metformin could significantly increase the abundance of Bacteroidetes and significantly reduce the abundance of Firmicutes and the ratio of Firmicutes/Bacteroidetes;at the family and genus levels,metformin could significantly increase the abundance of beneficial bacteria,such as Bacteroidaceae,Akkermansiaceae,Bifidobacterium and Roseburia while reduce the abundance of harmful bacteria such as Lachnospiraceae,Burkholderiaceae,Desulfovibrionaceae and Blautia.Line Discriminant Analysis Effect Size(LefSe): The structures of gut microbiome in obese PCOS patients were significantly different from the control group.Obese PCOS patients mainly had Firmicutes,Actinobacteria,Anaerolineae,etc.,while the important bacterias of the control group were Bacteroidetes,Clostridia,Gammaproteobacteria.In the Diane 35 group,the bacteria with significant changement in the intestine before treatment were the Firmicutes and Ruminococcaceae,which was Bacteroides after treatment.Prior to treatment,patients in the combined medication group had important flora including Firmicutes,Fusobacteria,Ruminococcaceae,Blautia,etc.After treatment,the bar graphs of Lachnospiraceae and Roseburia disappeared.Conclusion1.Diane 35 combined with metformin is better than Diane 35 monotherapy in improving the reproductive endocrine metabolism of obese PCOS patients.2.Metformin can change the structure of gut microbiome in obese PCOS patients,increase the relative abundance of beneficial flora such as Bacteroides,Akkermansiaceae,Bifidobacterium,Roseburia and reduce the abundance of some harmful flora such as Lachnospiraceae and Roseburia.The imbalance of gut microbiome can lead to obese PCOS.The changement of proportion of beneficial intestinal flora can improve the symptoms of obese PCOS patients on a certain extent.