The emerging role of the gut-testis axis in male reproductive health and infertility

•Mounting evidence suggests that the gut microbiome plays a key role in normal spermatogenesis and can be negatively impacted by diet and environmental perturbations. •Disruption of the gut microbiome may lead to impaired spermatogenesis via failure of the blood-testis barrier, seminal inflammation, oxidative stress, deoxyribonucleic acid damage, and impaired spermatogenesis. •Dietary changes, probiotics, omega-3 fatty acids, and lifestyle changes can restore a dysbiotic microbiome and improve male fertility. Male factor infertility continues to be a challenging condition with a significant proportion of men receiving no clear explanation for why they are unable to conceive. On the basis of the data presented in this review, there is now mounting evidence to support the role of the gut-testis axis in both healthy and diseased states, and at the core of this axis is the gut microbiome. Under nonpathological conditions, the gut microbiome maintains a symbiotic relationship with the testes. Disruption of the gut microbiome by diet or diseases initiates a chain reaction leading to diminishing fertility. Under dysbiotic conditions, there is an increase in inflammatory markers coupled with a loss of integrity of the gut epithelium leading to translocation of bacteria and inflammatory cytokines into systemic circulation. Ultimately, the testes along with the rest of the body are exposed to chronic inflammation because of this dysbiosis through pathways that remain to be fully elucidated. Eventually, this may also lead to loss of integrity of the blood-testis barrier causing impaired spermatogenesis and depressed semen parameters. Restoration of the gut microbiome to a symbiotic state via probiotics, fecal microbiota transplantation, bacteriophages, or small molecules may soon be able to decrease gut inflammation, rescue the integrity of the blood-testis barrier, and ultimately improve semen quality. Male factor infertility continues to be a challenging condition with a significant proportion of men receiving no clear explanation for why they are unable to conceive. On the basis of the data presented in this review, there is now mounting evidence to support the role of the gut-testis axis in both healthy and diseased states, and at the core of this axis is the gut microbiome. Under nonpathological conditions, the gut microbiome maintains a symbiotic relationship with the testes. Disruption of the gut microbiome by diet or diseases initiates a chain reaction leading to diminishing fertility. Under dysbiotic conditions, there is an increase in inflammatory markers coupled with a loss of integrity of the gut epithelium leading to translocation of bacteria and inflammatory cytokines into systemic circulation. Ultimately, the testes along with the rest of the body are exposed to chronic inflammation because of this dysbiosis through pathways that remain to be fully elucidated. Eventually, this may also lead to loss of integrity of the blood-testis barrier causing impaired spermatogenesis and depressed semen parameters. Restoration of the gut microbiome to a symbiotic state via probiotics, fecal microbiota transplantation, bacteriophages, or small molecules may soon be able to decrease gut inflammation, rescue the integrity of the blood-testis barrier, and ultimately improve semen quality.