Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes

Junpeng Yang; Xueli Yang; Guojun Wu; Fenglian Huang; Xiaoyang Shi; Wei Wei; Yingchao Zhang; Haihui Zhang; Lina Cheng; Lu Yu; Jing Shang; Yinghua Lv; Xiaobing Wang; Rui Zhai; Pan Li; Bota Cui; Yuanyuan Fang; Xinru Deng; Shasha Tang; Limin Wang; Qian Yuan; Liping Zhao; Faming Zhang; Chenhong Zhang; Huijuan Yuan

doi:10.1016/j.cmet.2023.06.010

Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes

Cell Metab. 2023 Sep 5;35(9):1548-1562.e7. doi: 10.1016/j.cmet.2023.06.010. Epub 2023 Jul 13.

Authors

Junpeng Yang¹, Xueli Yang¹, Guojun Wu², Fenglian Huang¹, Xiaoyang Shi¹, Wei Wei¹, Yingchao Zhang¹, Haihui Zhang³, Lina Cheng³, Lu Yu¹, Jing Shang¹, Yinghua Lv¹, Xiaobing Wang¹, Rui Zhai⁴, Pan Li⁵, Bota Cui⁵, Yuanyuan Fang¹, Xinru Deng¹, Shasha Tang¹, Limin Wang¹, Qian Yuan¹, Liping Zhao⁶, Faming Zhang⁷, Chenhong Zhang⁸, Huijuan Yuan⁹

Affiliations

¹ Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
² State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA.
³ Department of Gastroenterology of Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
⁴ State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China.
⁶ State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address: liping.zhao@rutgers.edu.
⁷ Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China. Electronic address: fzhang@njmu.edu.cn.
⁸ State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: zhangchenhong@sjtu.edu.cn.
⁹ Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China. Electronic address: hjyuan@zzu.edu.cn.

PMID: 37451270
DOI: 10.1016/j.cmet.2023.06.010

Abstract

The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.

Keywords: diabetes mellitus; distal symmetric polyneuropathy; fecal microbiota transplantation; guild; gut microbiome.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Diabetic Neuropathies* / drug therapy
Diabetic Neuropathies* / etiology
Diabetic Neuropathies* / pathology
Gastrointestinal Microbiome*
Humans
Polyneuropathies* / complications