Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.
Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.
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糖尿病前期绵羊睾丸细胞凋亡升高与肠道微生物群驱动的鞘氨醇升高相关
DOI：
10.1186/s12915-022-01326-y
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发表时间：
2022-05-24
期刊：
影响因子：
5.4
通讯作者：
Zhou, Yang
中科院分区：
文献类型：
--
作者：
Sun, Yuanchao;Sun, Peng;Hu, Yanting;Shan, Liying;Geng, Qi;Gong, Yutian;Fan, Haitao;Zhang, Teng;Zhou, Yang
关键词：
患有前驱糖尿病的男性通常伴有低质量精子产生甚至不育，这些问题迫切需要改进治疗方案。在这项研究中，我们建立了一个与生精缺陷相关的饮食诱导的前驱糖尿病羊模型，并探索了可能的潜在代谢原因。我们比较了饲喂正常饮食的公羊和饲喂丰富饮食诱发前驱糖尿病的公羊，以及饲喂丰富饮食补充褪黑激素的第三组公羊。只有饮食丰富的一组有前驱糖尿病的症状，在这些羊中，我们发现精子发生受损，其特征是圆形精子发育受阻，睾丸凋亡细胞数量增加。比较三组的肠道微生物组和肠道消化代谢组，发现糖尿病前期羊的微生物群分类组成存在显著差异，代谢组发生改变，其中最显著的特征是鞘氨醇代谢改变；在血液和睾丸中也发现了升高的鞘氨醇。褪黑素的施用减轻了前驱糖尿病的症状，包括精子发生受损的症状，同时恢复了更正常的微生物群和鞘氨醇代谢水平。前驱糖尿病羊的粪便微生物群移植在受体小鼠中诱导鞘氨醇水平升高和精子发生受损，表明肠道微生物群在这些表型中起因果作用。我们的研究结果指出鞘氨醇在糖尿病前期绵羊精子发生破坏中的关键作用，并表明它可能是一种有用的疾病标志物；此外，褪黑素是治疗由前驱糖尿病引起的男性不育的潜在益生元药物。在线版本包含补充材料，可在10.1186/s12915-022-01326-y获得。
Men with prediabetes often exhibit concomitant low-quality sperm production or even infertility, problems which urgently require improved therapeutic options. In this study, we have established a sheep model of diet-induced prediabetes that is associated with spermatogenic defects and have explored the possible underlying metabolic causes. We compared male sheep fed a normal diet with those in which prediabetes was induced by a rich diet and with a third group in which the rich diet was supplemented by melatonin. Only the rich diet group had symptoms of prediabetes, and in these sheep, we found impaired spermatogenesis characterized by a block in the development of round spermatids and an increased quantity of testicular apoptotic cells. Comparing the gut microbiomes and intestinal digest metabolomes of the three groups revealed a distinctive difference in the taxonomic composition of the microbiota in prediabetic sheep, and an altered metabolome, whose most significant feature was altered sphingosine metabolism; elevated sphingosine was also found in blood and testes. Administration of melatonin alleviated the symptoms of prediabetes, including those of impaired spermatogenesis, while restoring a more normal microbiota and metabolic levels of sphingosine. Fecal microbiota transplantation from prediabetic sheep induced elevated sphingosine levels and impaired spermatogenesis in recipient mice, indicating a causal role of gut microbiota in these phenotypes. Our results point to a key role of sphingosine in the disruption of spermatogenesis in prediabetic sheep and suggest it could be a useful disease marker; furthermore, melatonin represents a potential prebiotic agent for the treatment of male infertility caused by prediabetes. The online version contains supplementary material available at 10.1186/s12915-022-01326-y.
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影响因子：
4
作者：
Lestienne, P;Reynier, P;Rohmer, V
通讯作者：
Rohmer, V
影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
褪黑激素通过调节小鼠肠道微生物群来预防肥胖。
影响因子：
10.3
作者：
Xu, Pengfei;Wang, Jialin;Zhai, Yonggong
通讯作者：
Zhai, Yonggong
影响因子：
120.7
作者：
Menke, Andy;Casagrande, Sarah;Cowie, Catherine C.
通讯作者：
Cowie, Catherine C.
DOI：
10.1016/s0140-6736(12)60283-9
发表时间：
2012-06-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
Tabák AG;Herder C;Rathmann W;Brunner EJ;Kivimäki M
通讯作者：
Kivimäki M