Research progress in the treatment of diabetic neuropathic pain based on intestinal flora_West China Medical Journal

Authors：

WANG Weiwei ¹ ,  HE Zhijun ² , LIU Tao ² , HE Bo ¹ , MA Suilu ¹ , WEI Xiaotao ¹

1. Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730030, P. R. China;
2. Orthopedics of Foot and Ankle, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730050, P. R. China;

Corresponding author：

HE Zhijun, Email: hzj0931@126.com

Keywords：

Gut microbiota; diabetic neuropathic pain; traditional Chinese medicine

DOI：

10.7507/1002-0179.202211065

Video：

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Diabetic neuropathic pain (DNP) is one of the most common and complex complications of diabetes. In recent years, studies have shown that gut microbiota can regulate inflammatory response, intestinal permeability, glucose metabolism, and fatty acid oxidation, synthesis, and energy consumption by regulating factors such as lipopolysaccharides, short chain fatty acids, bile acids, and branched chain amino acids, achieving the goal of treating DNP. This paper summarizes the relevant mechanisms of gut microbiota in the treatment of DNP, the relevant intervention measures of traditional Chinese and western medicine, in order to provide new ideas for clinical treatment of DNP.

Citation： WANG Weiwei, HE Zhijun, LIU Tao, HE Bo, MA Suilu, WEI Xiaotao. Research progress in the treatment of diabetic neuropathic pain based on intestinal flora. West China Medical Journal, 2023, 38(6): 938-942. doi: 10.7507/1002-0179.202211065 Copy

1.	Zhang YH, Hu HY, Xiong YC, et al. Exercise for neuropathic pain: a systematic review and expert consensus. Front Med (Lausanne), 2021, 8: 756940.
2.	Shiferaw WS, Akalu TY, Work Y, et al. Prevalence of diabetic peripheral neuropathy in Africa: a systematic review and meta-analysis. BMC Endocr Disord, 2020, 20(1): 49.
3.	O’Connell TM. The application of metabolomics to probiotic and prebiotic interventions in human clinical studies. Metabolites, 2020, 10(3): 120.
4.	Morais LH, Schreiber HL 4th, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol, 2021, 19(4): 241-255.
5.	何志军, 魏晓涛, 张玉昌, 等. 中药干预糖尿病神经痛相关信号通路研究进展. 中国实验方剂学杂志, 2022, 28(17): 275-282.
6.	Pickard JM, Zeng MY, Caruso R, et al. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev, 2017, 279(1): 70-89.
7.	Lee CB, Chae SU, Jo SJ, et al. The relationship between the gut microbiome and metformin as a key for treating type 2 diabetes mellitus. Int J Mol Sci, 2021, 22(7): 3566.
8.	巴茜远, 郝悦, 肖礼祖, 等. 肠道菌群调控慢性疼痛机制的研究进展. 中国微生态学杂志, 2022, 34(3): 356-359.
9.	Guo R, Chen LH, Xing C, et al. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth, 2019, 123(5): 637-654.
10.	Chen W, Zhang M, Guo Y, et al. The profile and function of gut microbiota in diabetic nephropathy. Diabetes Metab Syndr Obes, 2021, 14: 4283-4296.
11.	Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine, 2020, 51: 102590.
12.	罗艺, 汪菲, 曾强. 基于肠道菌群的 2 型糖尿病发病机制及防治策略. 中国临床保健杂志, 2022, 25(3): 289-296.
13.	Chen P, Wang C, Ren YN, et al. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain, 2021, 14(1): 50.
14.	Li B, Fang J, Zuo Z, et al. Activation of porcine alveolar macrophages by actinobacillus pleuropneumoniae lipopolysaccharide via the toll-like receptor 4/NF-κB-mediated pathway. Infect Immun, 2018, 86(3): e00642-17.
15.	Dey P. Gut microbiota in phytopharmacology: a comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions. Pharmacol Res, 2019, 147: 104367.
16.	熊婷, 段家怀, 蒋小燕, 等. 阿托伐他汀对 T2DM 患者血清脂多糖及相关炎症因子的影响. 湖南师范大学学报(医学版), 2018, 15(2): 49-51.
17.	Vinolo MA, Rodrigues HG, Nachbar RT, et al. Regulation of inflammation by short chain fatty acids. Nutrients, 2011, 3(10): 858-876.
18.	李琳琳, 杨浩, 王烨. 肠道菌群代谢产物短链脂肪酸与 2 型糖尿病的关系. 新疆医科大学学报, 2017, 40(12): 1517-1521.
19.	Zhou F, Wang X, Han B, et al. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol Pain, 2021, 17: 1744806921996520.
20.	Perry RJ, Peng L, Barry NA, et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature, 2016, 534(7606): 213-217.
21.	Tirosh A, Calay ES, Tuncman G, et al. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci Transl Med, 2019, 11(489): eaav0120.
22.	顾冠聪, 周懿忆, 陈华. 糖尿病周围神经病变患者血清总胆汁酸和总胆红素水平变化及其诊断价值分析. 检验医学与临床, 2022, 19(24): 3396-3400.
23.	Wahlström A, Sayin SI, Marschall HU, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab, 2016, 24(1): 41-50.
24.	Yoon MS. mTOR as a key regulator in maintaining skeletal muscle mass. Front Physiol, 2017, 8: 788.
25.	Tian J, Liu C, Zheng X, et al. Porphyromonas gingivalis induces insulin resistance by increasing BCAA levels in mice. J Dent Res, 2020, 99(7): 839-846.
26.	Andersson-Hall U, Gustavsson C, Pedersen A, et al. Higher concentrations of BCAAs and 3-HIB are associated with insulin resistance in the transition from gestational diabetes to type 2 diabetes. J Diabetes Res, 2018, 2018: 4207067.
27.	Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med, 2011, 17(4): 448-453.
28.	Scheithauer TPM, Rampanelli E, Nieuwdorp M, et al. Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes. Front Immunol, 2020, 11: 571731.
29.	Li YJ, Chen X, Kwan TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid-mediated activation of g protein-coupled receptors GPR43 and GPR109A. J Am Soc Nephrol, 2020, 31(6): 1267-1281.
30.	Li XX, Zhang XX, Zhang R, et al. Gut modulation based anti-diabetic effects of carboxymethylated wheat bran dietary fiber in high-fat diet/streptozotocin-induced diabetic mice and their potential mechanisms. Food Chem Toxicol, 2021, 152: 112235.
31.	Eslami M, Bahar A, Hemati M, et al. Dietary pattern, colonic microbiota and immunometabolism interaction: new frontiers for diabetes mellitus and related disorders. Diabet Med, 2021, 38(2): e14415.
32.	Salgaço MK, Oliveira LGS, Costa GN, et al. Relationship between gut microbiota, probiotics, and type 2 diabetes mellitus. Appl Microbiol Biotechnol, 2019, 103(23/24): 9229-9238.
33.	Tiderencel KA, Hutcheon DA, Ziegler J. Probiotics for the treatment of type 2 diabetes: a review of randomized controlled trials. Diabetes Metab Res Rev, 2020, 36(1): e3213.
34.	Sanders ME, Merenstein DJ, Reid G, et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 605-616.
35.	鲍哲, 杨升伟, 柯赛赛, 等. 益生元对 2 型糖尿病患者糖脂代谢的影响. 医学信息, 2018, 31(18): 132-134.
36.	Ma P, Mo R, Liao H, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice. J Neuroinflammation, 2022, 19(1): 169.
37.	Liu L, Zhang J, Cheng Y, et al. Gut microbiota: a new target for T2DM prevention and treatment. Front Endocrinol (Lausanne), 2022, 13: 958218.
38.	Jing Y, Yu Y, Bai F, et al. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome, 2021, 9(1): 59.
39.	祁悦, 张杰. 中医药治疗糖尿病周围神经病变的临床研究进展. 时珍国医国药, 2021, 32(2): 428-432.
40.	崔祥, 陶金华, 江曙, 等. 黄连提取物与肠道菌群的相互作用研究. 中草药, 2018, 49(9): 2103-2107.
41.	张芹, 周中凯, 张惠媛. 荞麦壳水提物调控糖尿病大鼠肠道菌群结构的研究. 中国粮油学报, 2017, 32(4): 31-36, 43.
42.	王文婷, 郭良清. 七味白术散通过调控肠道菌群改善 2 型糖尿病胰岛素抵抗的理论探讨. 西部中医药, 2022, 35(6): 56-59.

1. Zhang YH, Hu HY, Xiong YC, et al. Exercise for neuropathic pain: a systematic review and expert consensus. Front Med (Lausanne), 2021, 8: 756940.
2. Shiferaw WS, Akalu TY, Work Y, et al. Prevalence of diabetic peripheral neuropathy in Africa: a systematic review and meta-analysis. BMC Endocr Disord, 2020, 20(1): 49.
3. O’Connell TM. The application of metabolomics to probiotic and prebiotic interventions in human clinical studies. Metabolites, 2020, 10(3): 120.
4. Morais LH, Schreiber HL 4th, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol, 2021, 19(4): 241-255.
5. 何志军, 魏晓涛, 张玉昌, 等. 中药干预糖尿病神经痛相关信号通路研究进展. 中国实验方剂学杂志, 2022, 28(17): 275-282.
6. Pickard JM, Zeng MY, Caruso R, et al. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev, 2017, 279(1): 70-89.
7. Lee CB, Chae SU, Jo SJ, et al. The relationship between the gut microbiome and metformin as a key for treating type 2 diabetes mellitus. Int J Mol Sci, 2021, 22(7): 3566.
8. 巴茜远, 郝悦, 肖礼祖, 等. 肠道菌群调控慢性疼痛机制的研究进展. 中国微生态学杂志, 2022, 34(3): 356-359.
9. Guo R, Chen LH, Xing C, et al. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth, 2019, 123(5): 637-654.
10. Chen W, Zhang M, Guo Y, et al. The profile and function of gut microbiota in diabetic nephropathy. Diabetes Metab Syndr Obes, 2021, 14: 4283-4296.
11. Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine, 2020, 51: 102590.
12. 罗艺, 汪菲, 曾强. 基于肠道菌群的 2 型糖尿病发病机制及防治策略. 中国临床保健杂志, 2022, 25(3): 289-296.
13. Chen P, Wang C, Ren YN, et al. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain, 2021, 14(1): 50.
14. Li B, Fang J, Zuo Z, et al. Activation of porcine alveolar macrophages by actinobacillus pleuropneumoniae lipopolysaccharide via the toll-like receptor 4/NF-κB-mediated pathway. Infect Immun, 2018, 86(3): e00642-17.
15. Dey P. Gut microbiota in phytopharmacology: a comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions. Pharmacol Res, 2019, 147: 104367.
16. 熊婷, 段家怀, 蒋小燕, 等. 阿托伐他汀对 T2DM 患者血清脂多糖及相关炎症因子的影响. 湖南师范大学学报(医学版), 2018, 15(2): 49-51.
17. Vinolo MA, Rodrigues HG, Nachbar RT, et al. Regulation of inflammation by short chain fatty acids. Nutrients, 2011, 3(10): 858-876.
18. 李琳琳, 杨浩, 王烨. 肠道菌群代谢产物短链脂肪酸与 2 型糖尿病的关系. 新疆医科大学学报, 2017, 40(12): 1517-1521.
19. Zhou F, Wang X, Han B, et al. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol Pain, 2021, 17: 1744806921996520.
20. Perry RJ, Peng L, Barry NA, et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature, 2016, 534(7606): 213-217.
21. Tirosh A, Calay ES, Tuncman G, et al. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci Transl Med, 2019, 11(489): eaav0120.
22. 顾冠聪, 周懿忆, 陈华. 糖尿病周围神经病变患者血清总胆汁酸和总胆红素水平变化及其诊断价值分析. 检验医学与临床, 2022, 19(24): 3396-3400.
23. Wahlström A, Sayin SI, Marschall HU, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab, 2016, 24(1): 41-50.
24. Yoon MS. mTOR as a key regulator in maintaining skeletal muscle mass. Front Physiol, 2017, 8: 788.
25. Tian J, Liu C, Zheng X, et al. Porphyromonas gingivalis induces insulin resistance by increasing BCAA levels in mice. J Dent Res, 2020, 99(7): 839-846.
26. Andersson-Hall U, Gustavsson C, Pedersen A, et al. Higher concentrations of BCAAs and 3-HIB are associated with insulin resistance in the transition from gestational diabetes to type 2 diabetes. J Diabetes Res, 2018, 2018: 4207067.
27. Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med, 2011, 17(4): 448-453.
28. Scheithauer TPM, Rampanelli E, Nieuwdorp M, et al. Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes. Front Immunol, 2020, 11: 571731.
29. Li YJ, Chen X, Kwan TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid-mediated activation of g protein-coupled receptors GPR43 and GPR109A. J Am Soc Nephrol, 2020, 31(6): 1267-1281.
30. Li XX, Zhang XX, Zhang R, et al. Gut modulation based anti-diabetic effects of carboxymethylated wheat bran dietary fiber in high-fat diet/streptozotocin-induced diabetic mice and their potential mechanisms. Food Chem Toxicol, 2021, 152: 112235.
31. Eslami M, Bahar A, Hemati M, et al. Dietary pattern, colonic microbiota and immunometabolism interaction: new frontiers for diabetes mellitus and related disorders. Diabet Med, 2021, 38(2): e14415.
32. Salgaço MK, Oliveira LGS, Costa GN, et al. Relationship between gut microbiota, probiotics, and type 2 diabetes mellitus. Appl Microbiol Biotechnol, 2019, 103(23/24): 9229-9238.
33. Tiderencel KA, Hutcheon DA, Ziegler J. Probiotics for the treatment of type 2 diabetes: a review of randomized controlled trials. Diabetes Metab Res Rev, 2020, 36(1): e3213.
34. Sanders ME, Merenstein DJ, Reid G, et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 605-616.
35. 鲍哲, 杨升伟, 柯赛赛, 等. 益生元对 2 型糖尿病患者糖脂代谢的影响. 医学信息, 2018, 31(18): 132-134.
36. Ma P, Mo R, Liao H, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice. J Neuroinflammation, 2022, 19(1): 169.
37. Liu L, Zhang J, Cheng Y, et al. Gut microbiota: a new target for T2DM prevention and treatment. Front Endocrinol (Lausanne), 2022, 13: 958218.
38. Jing Y, Yu Y, Bai F, et al. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome, 2021, 9(1): 59.
39. 祁悦, 张杰. 中医药治疗糖尿病周围神经病变的临床研究进展. 时珍国医国药, 2021, 32(2): 428-432.
40. 崔祥, 陶金华, 江曙, 等. 黄连提取物与肠道菌群的相互作用研究. 中草药, 2018, 49(9): 2103-2107.
41. 张芹, 周中凯, 张惠媛. 荞麦壳水提物调控糖尿病大鼠肠道菌群结构的研究. 中国粮油学报, 2017, 32(4): 31-36, 43.
42. 王文婷, 郭良清. 七味白术散通过调控肠道菌群改善 2 型糖尿病胰岛素抵抗的理论探讨. 西部中医药, 2022, 35(6): 56-59.

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