小柯机器人

英国伦敦帝国理工学院Simone Di Giovanni团队近期取得重要工作进展，他们研究发现肠道代谢物吲哚-3-丙酸（IPA）可以促进神经再生和修复。这一研究成果2022年6月22日在线发表于《自然》杂志上。

在这里，研究人员表明间歇性禁食（IF）通过一种意想不到的机制促进小鼠坐骨神经挤压后的轴突再生，这种机制依赖于革兰氏阳性肠道微生物组和血清中肠道细菌衍生代谢物吲哚-3-丙酸 (IPA) 的增加。产芽胞梭状芽胞杆菌产生IPA是有效的轴突再生所必需的，并且在坐骨神经损伤后递送IPA可显著增强轴突再生，加速感觉功能的恢复。从机制上讲，来自坐骨背根神经节的RNA测序分析表明中性粒细胞趋化性在IPA依赖性再生表型中起作用，这通过抑制中性粒细胞趋化得到证实。他们的结果证明了微生物组衍生代谢物（如IPA），能够通过免疫介导机制促进感觉轴突的再生和功能恢复。

据介绍，哺乳动物周围神经系统神经元损伤后的再生潜力受到轴突再生速度缓慢的限制。再生能力受损伤依赖性和不依赖性机制的影响。在损伤不依赖性的机制中，环境因素如运动和环境富集已被证明会影响促进轴突再生的信号通路。其中一些途径，包括基因转录和蛋白质合成的修饰，线粒体代谢和神经营养素的释放，可以被间歇性禁食（IF）激活。然而，IF是否影响轴突再生能力仍有待研究。

附：英文原文

Title: The gut metabolite indole-3 propionate promotes nerve regeneration and repair

Author: Serger, Elisabeth, Luengo-Gutierrez, Lucia, Chadwick, Jessica S., Kong, Guiping, Zhou, Luming, Crawford, Greg, Danzi, Matt C., Myridakis, Antonis, Brandis, Alexander, Bello, Adesola Temitope, Mller, Franziska, Sanchez-Vassopoulos, Alexandros, De Virgiliis, Francesco, Liddell, Phoebe, Dumas, Marc Emmanuel, Strid, Jessica, Mani, Sridhar, Dodd, Dylan, Di Giovanni, Simone

Issue&Volume: 2022-06-22

Abstract: The regenerative potential of mammalian peripheral nervous system neurons after injury is critically limited by their slow axonal regenerative rate1. Regenerative ability is influenced by both injury-dependent and injury-independent mechanisms2. Among the latter, environmental factors such as exercise and environmental enrichment have been shown to affect signalling pathways that promote axonal regeneration3. Several of these pathways, including modifications in gene transcription and protein synthesis, mitochondrial metabolism and the release of neurotrophins, can be activated by intermittent fasting (IF)4,5. However, whether IF influences the axonal regenerative ability remains to be investigated. Here we show that IF promotes axonal regeneration after sciatic nerve crush in mice through an unexpected mechanism that relies on the gram-positive gut microbiome and an increase in the gut bacteria-derived metabolite indole-3-propionic acid (IPA) in the serum. IPA production by Clostridium sporogenes is required for efficient axonal regeneration, and delivery of IPA after sciatic injury significantly enhances axonal regeneration, accelerating the recovery of sensory function. Mechanistically, RNA sequencing analysis from sciatic dorsal root ganglia suggested a role for neutrophil chemotaxis in the IPA-dependent regenerative phenotype, which was confirmed by inhibition of neutrophil chemotaxis. Our results demonstrate the ability of a microbiome-derived metabolite, such as IPA, to facilitate regeneration and functional recovery of sensory axons through an immune-mediated mechanism.

DOI: 10.1038/s41586-022-04884-x

Source: https://www.nature.com/articles/s41586-022-04884-x

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