The potential influence and intervention measures of gut microbiota on sperm: it is time to focus on testis-gut microbiota axis

Abstract

As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality.

Keywords: dual impact; gut microbiota; intervention measures; mechanism; sperm motility; spermatogenesis; testis-gut microbiota axis.

Figure 1

Typical gut microbiota metabolites from different sources. According to different sources, these metabolites can be divided into three main types: 1. Metabolites directly produced by the gut microbiota from the diet: short chain fatty acids (SCFAs), polyunsaturated fatty acids (PUFAs) amino acid derivatives, and indole derivatives; 2. Metabolites produced by the host and modified by the gut micro- biota, secondary bile acids and hydroxysteroid dehydrogenases (HSDH); 3 Metabolites synthesized from novel LPS, polysaccharide A, and vitamin K, etc. The metabolites of GM may influence the host’s Spermatogenesis and motility.

Figure 2

probiotics, prebiotics and synbiotics. Probiotics refer to beneficial live microorganisms that improve host health conditions. Common types include Lacto- bacillus acidophilus, Bifidobacterium, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, and yeast such as Saccharomyces boulardii. Other probiotics like Streptococcus thermophilus are also recognized for their beneficial effects on host health. Prebiotics refer to food components that cannot be digested or absorbed by the host but can be utilized by beneficial gut bacteria, thereby promoting the growth or activity of probiotics. Common prebiotics include Inulin, fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), xylo-oligosac- chandes (XOS), chitosan-oligosaccharides (COS), and pectin-oligosaccharides (POS). Synbiotics refer to products combining probiotics and prebiotics that coexist and interact synergistically. Synbiotics contribute to enhancing gut microbiota by delivering probiotics (live beneficial microorganisms) and prebiotics (compounds that foster probiotic growth).

Figure 3

Potential mechanisms and intervention measures of GM influence sperm. Potential mechanisms of GM on sperm encompass immune modulation, inflammatory responses mediated by endo- toxins, oxidative stress, antioxidant defenses, metabolites of GM, epigenetic modifications, regulatory sex hormone signaling Interventions such as probiotics, prebiotics, synbiotics, FMT, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance spermatogenesis and motility.