Disrupted spermatogenesis in a metabolic syndrome model: the role of vitamin A metabolism in the gut-testis axis.
Disrupted spermatogenesis in a metabolic syndrome model: the role of vitamin A metabolism in the gut-testis axis.
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代谢综合征模型中精子发生中断：维生素 A 代谢在肠道-睾丸轴中的作用
DOI：
10.1136/gutjnl-2020-323347
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发表时间：
2022-01
期刊：
影响因子：
24.5
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Zhang T;Sun P;Geng Q;Fan H;Gong Y;Hu Y;Shan L;Sun Y;Shen W;Zhou Y
饮食诱导的肠道微生物区系失调的影响远远超出肠道。我们的目标是揭示在生精障碍的病因学中涉及肠道-睾丸轴的直接证据。建立了高能量饮食诱导的代谢综合征(METS)绵羊模型。对睾丸标本、寄主代谢物和肠道微生物组进行分析。粪便微生物区系移植(FMT)证实了肠道微生物区系与精子发生之间的联系。我们证明，在Mets模型中，使用10×单细胞RNA-seq可显著增加精原细胞的滞留数量。此外，通过代谢组学和16S rDNA序列分析，我们发现肠道对维生素A的吸收由于胆汁酸水平的显著降低而被取消，这与瘤胃球菌科_NK4A214_群的丰度降低显著相关。值得注意的是，维生素A的异常代谢效应可通过循环血液转移到睾丸细胞，这导致了精子发生异常，FMT证实了这一点。这些发现确定了通过宿主代谢物将睾丸功能和肠道微生物区系调节联系起来的起点，并将对蛋氨酸男性不育的治疗具有潜在价值。
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. 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. 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. 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.
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