Gut Microbial Genetic Variation Regulates Host Reproduction

Area of Science:

• Microbiology
• Reproductive Biology
• Genetics

Background:

• The gut-testis axis highlights the influence of gut microbes on host reproduction.
• The precise role of microbial genetic variation in this axis is not well understood.
• Cyclophosphamide (CTX) is known to induce male reproductive toxicity.

Purpose of the Study:

• To investigate the impact of microbial genetic variation on host reproduction.
• To identify specific gut microbial strains that can mitigate reproductive disorders.
• To explore potential therapeutic applications for CTX-induced male reproductive toxicity.

Main Methods:

• Utilized Caenorhabditis elegans (C. elegans) as a model organism.
• Screened 46 Escherichia coli (E. coli) strains for their effects on C. elegans fertility.
• Developed and validated engineered probiotics in a mouse model of CTX-induced reproductive toxicity.
• Performed comprehensive metabolome and transcriptome analyses.

Main Results:

• Identified 46 E. coli strains that enhanced C. elegans fertility.
• Found 26 mutant E. coli strains capable of mitigating CTX-induced reproductive issues in C. elegans.
• An engineered probiotic, Ecn Δpal, significantly improved spermatogenesis in mice with CTX-induced reproductive disorders.
• Metabolome and transcriptome data implicated purine metabolism in ameliorating CTX-induced male reproductive toxicity.

Conclusions:

• Gut microbial genetic variation plays a significant role in host reproduction.
• Specific E. coli strains and their variants show potential as probiotics for reproductive health.
• Purine metabolism is a key pathway involved in mitigating CTX-induced male reproductive toxicity.
• This study offers novel insights and therapeutic strategies for male reproductive toxicity.