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

Journal: Cell metabolism 2023;35(9):1548-1562.e7

PMID: 37451270

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

Distal symmetric polyneuropathy (DSPN) is the most common complication associated with diabetes, which can lead to pain, numbness, and weakness or tingling in the limbs or parts of the body. There are no cures for DSPN only drugs to manage symptoms, highlighting a need for further research. Recently it has been shown that the gut microbiota of individuals with DSPN differs to that of healthy individuals, but it is unclear as to the significance of this. This randomised control trial aimed to determine the effect of transplanting faecal microbiota from healthy individuals into those with DSPN. The results showed that DSPN was associated with a decreased abundance of beneficial gut bacteria and an increased abundance of pathogenic bacteria. Furthermore, compared to placebo, DSPN was alleviated in all 22 patients who received a faecal microbiota transplant from healthy subjects. There was an increase in gut microbiota associated with the production of beneficial short chain fatty acids and a decrease in toxin production. It was concluded that dysbiosis in the gut microbiota contributes to DSPN, which can be alleviated by faecal microbial transplant from healthy individuals. This study could be used by healthcare professionals to understand that the gut microbiota has an important role in DSPN. Further larger studies would be warranted before recommending faecal microbial transplant to individuals with this disorder.

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.

Address: 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.; 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.; Department of Gastroenterology of Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.; 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.; 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.; 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: [email protected].; 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: [email protected].; 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: [email protected].; 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: [email protected].

DOI: 10.1016/j.cmet.2023.06.010