Roseburia intestinalis-derived butyrate alleviates neuropathic pain

Yanjun Jiang; Ziheng Huang; Wuping Sun; Jiabin Huang; Yunlong Xu; Yuliang Liao; Tingting Jin; Qing Li; Idy Hiu Ting Ho; Yidan Zou; Wenyi Zhu; Qian Li; Fenfen Qin; Xinyi Zhang; Shuqi Shi; Na Zhang; Shaomin Yang; Wenhui Xie; Songbin Wu; Likai Tan; Lin Zhang; Huarong Chen; Tony Gin; Matthew Tak Vai Chan; William Ka Kei Wu; Lizu Xiao; Xiaodong Liu

doi:10.1016/j.chom.2024.11.013

Roseburia intestinalis-derived butyrate alleviates neuropathic pain

Cell Host Microbe. 2024 Dec 12:S1931-3128(24)00444-X. doi: 10.1016/j.chom.2024.11.013. Online ahead of print.

Authors

Yanjun Jiang¹, Ziheng Huang¹, Wuping Sun², Jiabin Huang², Yunlong Xu³, Yuliang Liao², Tingting Jin¹, Qing Li⁴, Idy Hiu Ting Ho¹, Yidan Zou¹, Wenyi Zhu⁵, Qian Li¹, Fenfen Qin¹, Xinyi Zhang¹, Shuqi Shi², Na Zhang¹, Shaomin Yang², Wenhui Xie², Songbin Wu², Likai Tan¹, Lin Zhang⁶, Huarong Chen¹, Tony Gin¹, Matthew Tak Vai Chan⁷, William Ka Kei Wu⁸, Lizu Xiao⁹, Xiaodong Liu¹⁰

Affiliations

¹ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
² Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, National Key Clinical Pain Medicine of China, Shenzhen 518060, China.
³ Shenzhen Key Laboratory of Drug Addiction, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Neonatology, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen 518055, China.
⁴ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Dermatology Hospital, Southern Medical University, Guangzhou, China.
⁵ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁶ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁷ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: mtvchan@cuhk.edu.hk.
⁸ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease Institute of Digestive Disease and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: wukakei@cuhk.edu.hk.
⁹ Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, National Key Clinical Pain Medicine of China, Shenzhen 518060, China. Electronic address: nsyyjoe@live.cn.
¹⁰ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: xdliu@cuhk.edu.hk.

PMID: 39706182
DOI: 10.1016/j.chom.2024.11.013

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.