Wuzi Yanzong Pill alleviates spermatogenesis dysfunction by modulating the gut microbial tryptophan metabolites

化学 精子发生 肠道菌群 失调 代谢组学 生物 药理学 内科学 内分泌学 生物化学 生物信息学 医学
作者
Juan Liu,Wuwen Feng,Dandan Zhang,Hao Cheng,Yaochuan Zhou,Jing Wu,Zixuan Wang,Zhilei Wang,Chunyan Fang,Guangsen Li,Yaodong You,Xujun Yu,Degui Chang
出处
期刊:Arabian Journal of Chemistry [Elsevier]
卷期号:17 (7): 105809-105809
标识
DOI:10.1016/j.arabjc.2024.105809
摘要

Wuzi Yanzong Pill (WZYZP), a classic traditional Chinese medicine prescription, has been widely used to alleviate spermatogenesis dysfunction for hundreds of years. However, the molecular mechanisms of WZYZP treatment for spermatogenesis dysfunction remain limited. Here, our results showed that WZYZP significantly improved spermatogenesis and testicular energy metabolism. The 16S rDNA sequencing showed that WZYZP improved gut microbiota dysbiosis, including increased relative abundances of Lactobacillus with the capability of metabolizing Trp. The depletion of gut microbiota by antibiotics suppressed the ability of WZYZP to improve spermatogenesis dysfunction. The untargeted and targeted metabolomics results showed that WZYZP increased Trp metabolites especially aryl hydrocarbon receptor (AhR) ligands. Moreover, WZYZP modulated the AhR/AMPK pathway to improve the expression of spermatogenesis-related genes. The correlation analysis showed that gut microbiota was significantly correlated with Trp metabolites, and Trp metabolites were closely related to spermatogenesis. Overall, the results demonstrated that WZYZP could regulate gut microbiota, and the gut microbial Trp metabolites further act on testicular energy metabolism, thereby indirectly improving spermatogenic dysfunction. Our study provides a novel research strategy for complementary and alternative medicine in male infertility from the perspective of gut microbial metabolites.
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