Study Of Gut Microbiota In Erectile Dysfunction Patients With Type 2 Diabetes Mellitus

Objective: To investigate the gut microbiota changes in type 2 Diabetic Erectile Dysfunction(DED)and type 2 diabetes without erectile dysfunction(NED),to investigate the correlation between gut microbiota changes and clinical characteristics and erectile function indicators,and to screen for potential genus markers,in order to provide new diagnostic and therapeutic ideas for the early detection of DED.The study will provide new research ideas for early diagnosis and treatment of DED.Methods: Thirty-seven patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology and Metabolism of Changzhou Second People’s Hospital from March 2021 to May 2022 were selected for inclusion in the study based on the inclusion criteria.General clinical data were collected,including age,blood pressure,BMI,duration of diabetes mellitus,history of smoking,history of alcohol consumption,history of previous chronic diseases,and complications of diabetes mellitus.Peripheral blood samples were collected for glycosylated hemoglobin A1c(Hb A1c),connecting peptide(C-P),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c),fasting plasma glucose(FPG),testosterone(TO),and serum uric acid(SUA)etc,and morning urine was collected for urinary microalbumin/urinary creatinine(UA/CR).Patients were divided into diabetic ED group(DED group)and diabetic non-ED group(NED group)according to the results of Rigiscan penile stiffness measurement,and stool samples were collected and amplicon sequencing was performed using 16 Sr DNA technology to analyze the structure and differences of intestinal flora between the two groups.Then linear discriminant analysis Effect Size(LEf Se)was used to find the differential flora between groups,and Spearman correlation analysis was performed to analyze the correlation between intestinal flora and clinical indicators as well as erectile function;a random forest model was constructed at the genus level to screen for important species;followed by the use of PICRUSt(Phylogenetic Investigation Communities by Reconstruction of Unobserved States)software was then used to predict the functional differences in intestinal flora between the two groups.Results:1.The final 37 male type 2 diabetic patients were included,and the patients were divided into 2 groups according to the NPTR test index,including 19 in the DED group and 18 in the NED group.There was no statistical difference between the two groups in terms of general information such as history of smoking,history of alcohol consumption,history of hypertension,diabetic nephropathy,diabetic peripheral neuropathy and incidence of diabetic peripheral vascular disease(P > 0.05),while the incidence of diabetic retinopathy was significantly higher in the DED group than in the NED group(P < 0.05).2.Alpha diversity of the flora showed significant differences between the two groups.Compared with the NED group,the richness of the flora and the total number of species were significantly lower in the DED group(P < 0.05),and there was no significant difference in species diversity(P > 0.05).Beta diversity showed significant differences in the structure of the gut microbiota between the two groups.At the phylum level,Firmicutes,Bacteroidetes,Proteobacteria and Actinobacteria were not significantly different between the two groups,and the abundance of Acidobacteria and Verrucomicrobia was significantly lower compared to the NED group;At the genus level,there was a statistically significant increase in the abundance of Bacteroides,Megamonas and Parabacteroide and a decrease in the relative abundance of Prevotella 9in the DED group(P < 0.05).3.Lef Se analysis showed that compared with the NED group,the DED group Tenericutes,Bacteroidaceae,Rikenellaceae,Tannerellaceae,Bacteroides,Alistipes,Parabacteroide,Ruminococcaceae NK4A214 group,Lachnoclostridium and other significant enrichment.NED group Acidobacteria,Cyanobacteria,Chloroflexi,Verrucomicrobia,Gemmatimonadetes,Prevotellaceae,Microscillaceae,Akkermansiaceae,Prevotella 9,Megamonas,Pediococcus,Megasphaera,Akkermansia and other significant enrichment.4.Spearman correlation analysis showed that a number of bacteria significantly enriched in the NED group were positively correlated with NPTR detection indicators,among which Streptomyces,Ruminiclostridium 6,Megamonas and Megasphaera were negatively correlated with UA/CR,Devosia was negatively correlated with Hb A1 C,and Pediococcus was negatively correlated with white blood cell count.A number of bacterial genera significantly enriched in the DED group were negatively correlated with NPTR detection indexes,among which Bacteroides,Parabacteroides were strongly positively correlated with UA/CR,Bacteroides showed a significant positive correlation with Hb A1 C,Anaerostipes were negatively correlated with TSH and FT4,[Ruminococcus] gauvreauii group was positively correlated with blood uric acid levels,and Lachnoclostridium was negatively correlated with TO levels.Correlation analysis of gut microbiota and α diversity showed that multiple genera significantly enriched in NED group were positively correlated with richness indexes,among which Ruminiclostridium 6 was also positively correlated with diversity index.A number of bacterial genera significantly enriched in the DED group were negatively correlated with the richness index,among which Alistipes,Ruminococcaceae NK4A214 group,[Ruminococcus] gauvreauii group,and [Eubacterium] eligens group were positively correlated with diversity index.5.The results of the random forest model showed that a biomarker consisting of 22 genera had a good diagnostic effect on DED,with areas under the receiver operating curve(AUC)was 88%.6.The data were analyzed by PICRUSt software based on KEGG and COG databases for microbiota function differences,involving 5 metabolic pathways,KEGG DID group was significantly higher than NED group with 2 pathways,energy metabolism and carbohydrate metabolism pathway,COG DED group was significantly higher than NED group had 1pathway,which was a defense mechanism pathway.Conclusion: 1.The gut microbiota richness of the DED group showed a decreasing trend,and the microbiota structure changed at various taxonomic levels.2.Changes in gut microbiota correlate with erectile function,and there is a strong relationship between gut microbiota and DED.3.A biomarker consisting of 22 genera has a large diagnostic potential for DED.