The Association Of Gut Microbiota With Semen Quality

Male infertility has become a serious worldwide problem,and semen quality is one of the most basic and important indicators of male reproductive health.Previous studies have found that semen quality can be influenced by a combination of genetic and environmental factors.Recent studies further suggested that the stability of the gut microbiota may be associated with semen quality as well,but they have mainly focused on animal models or people with obesity.This study is the first exploratory study on the association between semen quality and gut microbiota focusing on healthy population,which may provide some clue to related future researches and data support for developing microbial biomarkers for semen quality.Objective: In this study,we attempted to investigate the association of gut microbiota with semen quality in a comparatively healthy population by investigating differences in the gut microbial structure and total bacterial load between people with high and low semen quality.Methods: Fecal and semen samples were collected from healthy volunteers aged22-45 who went to the Hubei Province Human Sperm Bank for pre-donation screening.Based on age(±3 years)and fecal sampling date(±4 weeks),we conducted a 1:3matched case-control study,obtaining 25 individuals with low semen quality(L)and matched 75 individuals with high semen quality(H).After fecal DNA extraction,the relative and absolute abundances of the microbial communities were obtained using16 S rRNA gene sequencing and q PCR.Correlation analyses were conducted between the screened differential microbes and semen quality parameters.Results: Compared with the H group,the microbial diversity of gut microbiota in the L group was significantly depleted.Meanwhile,there were also significant differences in gut microbial community structures between the H and L groups.A total of 31 differential ASVs were identified.Some beneficial bacteria were enriched in the H group,including Lachnospira spp.,Ruminococcus spp.,Roseburia faecis,Megamonas spp.,Veillonella dispar and Parabacteroides distasonis,while some opportunistic pathogenic bacteria were enriched in the L group,including Fusobacterium,Bacteroidetes ovatus,Sutterella spp.,and Prevotella copri.According to the correlation analysis,the total bacterial load was negatively correlated with sperm count and concentration.The total motility,forward motility and normal morphology were negatively correlated with the Bacteroidetes spp.The normal morphology was negatively correlated Prevotella copri.The total sperm count was positively correlated with Veillonella dispar.The g＿Lachnospira＿ASV8 might be the most promising biomarker for semen quality,which was significantly enriched in H group and also positively correlated with total sperm count.Besides,in the network analysis,we found more significant correlations between gut microbes in the H group reflecting more stable ecosystem than the L group.The L group had fewer predicted functional pathways compared with the H group.Conclusions: Gut microbial community structure and total load were associated with semen quality of healthy adult males.We detected several opportunistic pathogenic bacterial groups enriched in the L group and negatively correlated with semen quality.Some beneficial and commensal microorganisms were enriched in the H group and had positive correlations with semen quality.In particular,the most promising biomarker g＿Lachnospira＿ASV8,which was significantly enriched in H group,was positively correlated with the sperm count.This is an exploratory study on the association of gut microbiome with semen quality in comparatively healthy population,and it identified a series of potential gut microbes associated with semen quality,which may be used as potential biomarkers.Our findings still need further confirmation and subsequent studies requires a larger sample size and comprehensive metagenomic and metabolomic analyses.