再生(生物学)
细胞生物学
趋化性
生物
坐骨神经
神经损伤
再生医学
神经科学
生物化学
解剖
干细胞
受体
作者
Elisabeth Serger,L. Gutiérrez,Jessica Chadwick,Guiping Kong,Luming Zhou,Greg Crawford,Matt C. Danzi,Antonis Myridakis,Alexander Brandis,Adesola T. Bello,Franziska Müller,Alexandros Sanchez-Vassopoulos,Francesco De Virgiliis,Phoebe Liddell,Marc‐Emmanuel Dumas,Jessica Strid,Sridhar Mani,Dylan Dodd,Simone Di Giovanni
出处
期刊:Nature
[Springer Nature]
日期:2022-06-22
卷期号:607 (7919): 585-592
被引量:136
标识
DOI:10.1038/s41586-022-04884-x
摘要
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.
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