Men with nonobstructive azoospermia (NOA) face the dual problems of low sperm count and low sperm quality. Most men with NOA without a clear cause are classified as having idiopathic NOA (iNOA). Previous studies found that microbes exist in semen, and the semen microbes of NOA men are different from those of normal men. However, the relevant mechanism is not clear. In this study, we answered the three questions of "who is there," "what is it doing," and "who is doing it" by combining 16s rRNA, nontargeted metabolome detection and metabolite traceability analysis. We found that the composition and interaction of seminal plasma microbes in the iNOA group changed. Metabolite traceability analysis and metabolic pathway analysis revealed that microbial abnormalities in the NOA group were closely related to the decrease of microbial degradation of toluene and the increase of metabolism of fructose or mannose. In addition, the metabolic relationship between microbes and the host in male semen in iNOA revealed that such microbes can produce harmful metabolites that affect sperm quality, the microbes compete with sperm for essential nutrients, and their presence reduces sperm production of essential nutrients. IMPORTANCE Idiopathic nonobstructive azoospermia is one of the great challenges in assisted reproductive therapy. Although microdissection testicular sperm extraction technology is currently available, many men with iNOA still face the problem of poor sperm retrieval and poor sperm quality. The role of seminal plasma microbes in male disease has been continuously investigated since semen was demonstrated to harbor commensal microbes. To our knowledge, this is the first detailed description of the microbe-host relationship in iNOA semen. This study is an important complement to research on the treatment and etiology of iNOA and the rationale for our ongoing research.
Keywords: assisted reproductive technology; idiopathic nonobstructive azoospermia; infertility; metabolome; seminal microbiota; sperm.