Exploration of interaction and correlation between NH3 and H2S and gut microbiota (GM) on male infertility

Yanan Hao

Since the new century, declining fertility rates and male infertility have become a worldwide challenge. Many factors have been investigated related to male fertility. Many studies have suggested that harmful gases, such as NH3 (ammonia) and H2S (hydrogen sulfide) can cause male infertility, and gut microbiota showed a correlation with male fertility. The prevalence of unhealthy lifestyles is increasing chronic diseases which also lead to male infertility. Diabetes is a disease with multiple complications that seriously influences health generally and male infertility. An increasing number of other factors are reported to affect male infertility, with some being controversial. Here, I analysed information from the published literature and my own experimental results using a meta-analysis approach combined with bioinformatics to seek answers to causes of male fertility. There were three phases in the analyses. The first phase was the exploration of relationships between the gut microbiota and NH3 and/or H2S gases. The results demonstrated the underlying relationship between gut microbiota and inner NH3 or/and H2S and male infertility. The data suggested that species of Bacteroides and Lactobacillus show close interactions with inner NH3 and/or H2S gas production. Bacteroides was positively related to the amount of these gases (Z=8.55, p<0.00001) while Lactobacillus showed a negative relationship with the amount of these gases (Z=10.95, p<0.00001). This chapter proposed an interesting correlation among gut microbiota, inner NH3 and/or H2S and male fertility. To verify the relationship that we proposed in chapter one, the second phase focused on profiling gut dysbiosis associated with diabetes, which was identified by a meta-analysis that identified bacteria both positively and negatively correlated with diabetes. Based on the results of chapter two, we found that Lactobacillus (Z=4.98, p<0.00001) and Akkermansia (Z=6.61, p<0.00001) show a significantly decreasing trend in diabetes compared to the controls. Bacteroides (Z=0.99, p=0.32) and Bifidobacterium (Z=0.39, p=0.69) show an increasing trend in diabetes compared to the controls, but with no statistical significance. The third phase focused our investigation on the damage from diabetes that influenced male fertility and explored the underlying mechanism(s). We demonstrated that type 2 diabetes (Z=8.10, p<0.00001) showed a higher probability of causing male infertility than type 1 diabetes (Z=9.93, p<0.00001). Furthermore, inflammatory pathways were demonstrated to be involved in diabetes-induced male infertility in this chapter. In conclusion, there is a relationship among the gut flora, inner NH3 and/or H2S, and male fertility, moreover, the gut flora and inner NH3 and/or H2S were deeply correlated with diabetes which leads to male infertility. Different bacteria showed different roles and functions. Bacteroides appeared to have a negative influence on male fertility which positively related to the amount of NH3 and/or H2S in the gut, increasing in diabetics, while Lactobacillus might exert positive effects on male fertility while being negatively related to the amount of NH3 and/or H2S in the gut, and decreasing in diabetics. The mechanism of diabetes causing male infertility involves inflammatory pathways (TNF-α). This study proposes a novel method to understand the correlation between different research aspects and provide a valuable contribution to finding a potential research target for further investigation.

Exploration of interaction and correlation between NH3 and H2S and gut microbiota (GM) on male infertility

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