Gut-microbiota-testis axis: The mechanism of gut microbiota regulating host male reproduction
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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The gut-microbiota (GM)-testis axis lets gut bacteria regulate male reproduction via multiple key pathways.
GM-host interaction includes response to bacterial metabolites and direct interaction with bacteria themselves.
Extracellular vesicles (EVs) shuttle biomolecules to testes; testicular mitochondria mediate microbial effects.
Diet and lifestyle also play a role in this regulation, linking gut health to male reproductive function.
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ABSTRACT
Gut microbiota (GM), a dynamically changing community of bacterial species and other microorganisms, has become a crucial factor in host physiology. Mounting evidence indicates its communication with distal organs like the testis via intricate mechanisms, establishing the gut-microbiota-testis axis. This axis has emerged as a key focus in investigations into the regulation of male reproduction by GM. However, several critical aspects remain unaddressed comprehensively and systematically. There is a dearth of knowledge regarding the detailed characterization of GM components relevant to male reproduction. The mechanisms underlying the translocation of GM components to the testes remain poorly understood. Additionally, how GM impacts testicular function to modulate male reproductive processes has not been thoroughly investigated. Here, we reviewed the gut microbiota and gut-microbiota-testis axis and discussed the main mechanisms of GM regulating host male reproduction. It is noted that GM regulates host male reproduction through bacterial metabolites and/or direct interactions with the bacteria themselves. Moreover, extracellular vesicles (EVs) may serve as shuttle vehicles for transporting bioactive substances such as microbial metabolites, and testicular mitochondria can act as mediators for gut microbiota to regulate host male reproduction. Finally, gut microbiota is a highly dynamic and complex community that is influenced by factors such as diet, living environment, and lifestyle, which is of great significance for clinical interventions. This review will assist with clinical targeted intervention of GM and explore new therapies for male reproductive disorders.-
Keywords:
- gut microbiota /
- testis /
- gut-microbiota-testis axis /
- male reproduction /
- mechanisms
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Ding X., Zhu T., Gu R., et al. (2025). Gut-microbiota-testis axis: The mechanism of gut microbiota regulating host male reproduction. The Innovation Life 3:100158. https://doi.org/10.59717/j.xinn-life.2025.100158
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Ding X., Zhu T., Gu R., et al. (2025). Gut-microbiota-testis axis: The mechanism of gut microbiota regulating host male reproduction. The Innovation Life 3:100158. https://doi.org/10.59717/j.xinn-life.2025.100158
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Figure 1.
Modulation of host male reproduction by gut microbiota metabolites through five primary pathways
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Figure 2.
Mechanism by which bacterial-derived extracellular vesicles (EVs) act as mediators to transfer bioactive molecules (e.g., proteins, RNA, lipids) to host cells such as testicular cells
