Related Experiment Video

Updated: May 31, 2026

An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
07:15

An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota

Published on: July 31, 2019

Causal Effects of Gut Microbial Genera on Abnormal Spermatozoa Revealed Through Integrated Mendelian Randomization

Huixiang Yang1, Jing Gao2

  • 1Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

American Journal of Reproductive Immunology (New York, N.Y. : 1989)
|May 29, 2026
PubMed
Abstract

Insights

Specific gut bacteria genera are causally linked to abnormal sperm quality. This study identified both harmful and protective bacteria, suggesting new targets for male infertility treatments via the gut-testis axis.

Area of Science:

  • Microbiome research
  • Male reproductive health
  • Genetics

Background:

  • Sperm quality is crucial for fertility, and its abnormalities contribute to male infertility.
  • The gut microbiota's influence on systemic health is increasingly recognized, but its specific role in male reproductive function remains unclear.

Purpose of the Study:

  • To investigate the causal relationship between gut microbiota genera and abnormal spermatozoa (count, motility, morphology).
  • To explore potential mediating factors, including metabolic pathways, immune cell traits, and serum bioavailable testosterone (BioT).

Main Methods:

  • Utilized summary statistics from publicly available GWAS databases for gut microbiota, spermatozoa, and potential mediators.
  • Performed fixed-effects meta-analysis and two-sample Mendelian randomization (MR) analysis.
  • Employed a triangulation framework (MR, HyPrColoc, Steiger tests) for robust causal inference and mediation analysis.

Main Results:

  • Identified eight gut microbiota genera with significant causal associations with abnormal spermatozoa: four risk (Lachnospiraceae UCG001, Coprococcus, Barnesiella, Dorea) and four protective (Clostridium sensu stricto 1, Ruminiclostridium 6, Lachnospiraceae_noname, Veillonella).
  • Causal relationships were validated by the triangulation framework.
  • Mediation analysis did not confirm BioT, immune cells, or metabolic pathways as mediators, indicating novel gut-testis axis mechanisms.

Conclusions:

  • Established a large-scale causal connection between specific gut microbiota genera and abnormal spermatozoa.
  • The findings suggest "causation without colocalization" and novel gut-testis axes, pointing towards distant regulatory mechanisms.
  • These insights offer potential microbiota-targeted therapeutic strategies for addressing male infertility.
Keywords:
abnormal spermatozoagut microbiotagut‒testis axesmediation analysismendelian randomization

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