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, 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
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.
Conflict of interest statement
Declaration of interests L.Z. is a co-founder of Notitia Biotechnologies Company. F.Z. conceived the concept of GenFMTer and transendoscopic enteral tubing and devices related to them.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed