Roseburia intestinalis-derived butyrate alleviates neuropathic pain

Abstract

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.

Keywords: GPR41; Roseburia intestinalis; VZV-related pain; butyrate; gut microbiota; gut-brain axis.