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  2. Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis

Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis

  • Food Res Int. 2025 May:208:116218. doi: 10.1016/j.foodres.2025.116218.
Guitian He 1 Boqi Zhang 1 Tong Chen 1 Caomeihui Shen 1 Nan Wang 1 Junjun Yang 1 Fuqiang Chang 1 Yue Sui 1 Xuanqi Yin 1 Yueying Wang 1 Sihui Wang 1 Yaqiu Li 1 Jinxin Zong 1 Yuxin Luo 1 Yang Meng 2 Chunjin Li 3 Xu Zhou 4
Affiliations

Affiliations

  • 1 College of Animal Sciences, Jilin University, Changchun, Jilin, China.
  • 2 Jilin Province Product Quality Supervision and Inspection Institute, China.
  • 3 College of Animal Sciences, Jilin University, Changchun, Jilin, China. Electronic address: [email protected].
  • 4 College of Animal Sciences, Jilin University, Changchun, Jilin, China. Electronic address: [email protected].
Abstract

Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced Ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.

Keywords

Chitosan; Docosahexaenoic acid; Gut microbiota; Spermatogenesis.

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