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Gut microbiota
Original research
Disrupted spermatogenesis in a metabolic syndrome model: the role of vitamin A metabolism in the gut–testis axis
  1. Teng Zhang1,
  2. Peng Sun1,
  3. Qi Geng1,
  4. Haitao Fan1,
  5. Yutian Gong1,
  6. Yanting Hu1,
  7. Liying Shan1,
  8. Yuanchao Sun2,
  9. Wei Shen3,
  10. Yang Zhou1
  1. 1State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
  2. 2The Affiliated Hospital of Qingdao University and The Biomedical Sciences Institute of Qingdao University, Qingdao University, Qingdao, China
  3. 3College of Life Sciences, Qingdao Agricultural University, Qingdao, China
  1. Correspondence to Dr Yang Zhou, Inner Mongolia University, State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Hohhot, China; zhouyang106{at}126.com; Dr Teng Zhang; zhangteng428{at}163.com

Abstract

Objective Effects of the diet-induced gut microbiota dysbiosis reach far beyond the gut. We aim to uncover the direct evidence involving the gut–testis axis in the aetiology of impaired spermatogenesis.

Design An excessive-energy diet-induced metabolic syndrome (MetS) sheep model was established. The testicular samples, host metabolomes and gut microbiome were analysed. Faecal microbiota transplantation (FMT) confirmed the linkage between gut microbiota and spermatogenesis.

Results We demonstrated that the number of arrested spermatogonia was markedly elevated by using 10× single-cell RNA-seq in the MetS model. Furthermore, through using metabolomics profiling and 16S rDNA-seq, we discovered that the absorption of vitamin A in the gut was abolished due to a notable reduction of bile acid levels, which was significantly associated with reduced abundance of Ruminococcaceae_NK4A214_group. Notably, the abnormal metabolic effects of vitamin A were transferable to the testicular cells through the circulating blood, which contributed to abnormal spermatogenesis, as confirmed by FMT.

Conclusion These findings define a starting point for linking the testicular function and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of male infertility in MetS.

  • obesity
  • bile acid metabolism
  • vitamins

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. Data sets generated and analysed during this study are available from the corresponding author on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/gutjnl-2020-323347

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. Data sets generated and analysed during this study are available from the corresponding author on reasonable request.

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    Footnotes

    • TZ and PS contributed equally.

    • Contributors YZ designed and supervised the study; TZ, PS, QG, HF, YG, YH, LS and YS performed the experiments and analysed the data; YZ and TZ wrote the manuscript; YZ, TZ and WS contributed to the manuscript revision and discussion. All the authors read the manuscript and approved the final manuscript.

    • Funding This study was supported by the National Natural Science Foundation of China (31900595 to YZ; 32000582 to TZ), the opening project of the State Key Laboratory of R2BGL (SKL-IT-201810 to YZ; SKL-OT-201903 to TZ).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.