Correlation Between Gut Microbiota And Testosterone In Male Patients With Type 2 Diabetes Mellitus

Objective:The objective of this study was to investigate the association between testosterone levels and gut microbiota in male patients with type 2 diabetes mellitus（T2DM）and provide a new strategy to elucidate the pathological mechanism of testosterone deficiency in T2DM patients.Methods:Assessed male patients with diabetes who visited Shandong Provincial Hospital.The age,duration of T2DM,medical history,body mass index（BMI）,and hypertension of the participants were all documented.The peripheral venous blood and fecal samples of all subjects were collected.All individuals had blood tested in the morning after fasting for at least 8 hours the night before.The total testosterone,follicle-stimulating hormone（FSH）,luteinizing hormone（LH）,prolactin（PRL）,fasting blood glucose（FPG）,insulin（INS）,connecting peptide（C-P）,glycosylated hemoglobin A1c（HbA1c）,uric acid（URIC）,total cholesterol（TC）,triglyceride（TG）,low-density lipoprotein cholesterol（LDL-C）and C-reactive protein（CRP）were measured by Shandong provincial hospital.According to the US Endocrine Society recommendation（13,14）,a low testosterone level is defined as<2.8 ng/ml.The V3-V4 region of bacterial 16 S rDNA was amplified and sequenced.Alpha and Beta diversity were calculated by QIIME software.The effect size（LEfSe）of linear discriminant analysis（LDA）was utilized to find the bacterial taxa and metabolism-related clinical factors that differed significantly across groups.A comparison of the random forest model based on taxa composition was used to find important taxa.The possible association between gut microbial community and clinical indicators was assessed using the Spearman correlation coefficient.The association between the relative abundance of bacteria and testosterone levels was discovered using linear regression analysis in R language.Results:A total of 305 male patients with type 2 diabetes aged between 18 and 60 years were enrolled,and 46 male T2DM patients were analyzed according to the inclusion criteria and exclusion criteria.There was no substantial difference in alpha and beta diversity.Compared with the NT group,T2D men with low testosterone had a greater abundance of Massilia,Gemella,Solobacterium,Lachnoclostridium,Bergeyella,Blautia,Lachnospiraceae_UCG₀01,Allorhizobium_Neorhizobium_Pararhizobiu,Parvimonas and Actinoplanes at the genus level,yet Candidatus_Saccharimonas,Paludicola,and Allisonella were the most abundant species in NT group.Blautia and Lachnospirales were significantly much higher in the testosterone deficiency group.Linear regression analysis showed that the abundance of Lachnospirales at order level were negatively correlated with testosterone level.After corrected for C-reactive protein（CRP）and homeostatic model assessment of insulin resistance（HOMA-IR）,the relative abundance of Lachnospirales still had a significant negative correlation with testosterone level.Meanwhile,at the genus level,Lachnoclostridium,Blautia,and Bergeyella had a statistically significant negative association with testosterone level,respectively.Blautia was positively associated with FPG and total cholesterol level.Streptococcus was found positively associated with insulin,connecting peptide and index of homeostatic model assessment of insulin resistance.Conclusion:T2DM patients with testosterone deficiency have different gut microbiota compositions compared with T2DM patients alone.Low serum testosterone patients tend to have an increased abundance of opportunistic pathogens.The Lachnospirales,which are closely associated with metabolic diseases,were also significantly negatively associated with testosterone levels.This may be related to the occurrence and development of testosterone deficiency.