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.	何志軍, 魏曉濤, 張玉昌, 等. 中藥干預糖尿病神經痛相關信號通路研究進展. 中國實驗方劑學雜志, 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.	巴茜遠, 郝悅, 肖禮祖, 等. 腸道菌群調控慢性疼痛機制的研究進展. 中國微生態學雜志, 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.	羅藝, 汪菲, 曾強. 基于腸道菌群的 2 型糖尿病發病機制及防治策略. 中國臨床保健雜志, 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, 段家懷, 蔣小燕, 等. 阿托伐他汀對 T2DM 患者血清脂多糖及相關炎癥因子的影響. 湖南師范大學學報(醫學版), 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, 楊浩, 王燁. 腸道菌群代謝產物短鏈脂肪酸與 2 型糖尿病的關系. 新疆醫科大學學報, 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.	顧冠聰, 周懿憶, 陳華. 糖尿病周圍神經病變患者血清總膽汁酸和總膽紅素水平變化及其診斷價值分析. 檢驗醫學與臨床, 2022, 19(24): 3396-3400.
23.	Wahlstr?m 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.	Salga?o 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.	鮑哲, 楊升偉, 柯賽賽, 等. 益生元對 2 型糖尿病患者糖脂代謝的影響. 醫學信息, 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.	祁悅, 張杰. 中醫藥治療糖尿病周圍神經病變的臨床研究進展. 時珍國醫國藥, 2021, 32(2): 428-432.
40.	崔祥, 陶金華, 江曙, 等. 黃連提取物與腸道菌群的相互作用研究. 中草藥, 2018, 49(9): 2103-2107.
41.	張芹, 周中凱, 張惠媛. 蕎麥殼水提物調控糖尿病大鼠腸道菌群結構的研究. 中國糧油學報, 2017, 32(4): 31-36, 43.
42.	王文婷, 郭良清. 七味白術散通過調控腸道菌群改善 2 型糖尿病胰島素抵抗的理論探討. 西部中醫藥, 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. 何志軍, 魏曉濤, 張玉昌, 等. 中藥干預糖尿病神經痛相關信號通路研究進展. 中國實驗方劑學雜志, 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. 巴茜遠, 郝悅, 肖禮祖, 等. 腸道菌群調控慢性疼痛機制的研究進展. 中國微生態學雜志, 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. 羅藝, 汪菲, 曾強. 基于腸道菌群的 2 型糖尿病發病機制及防治策略. 中國臨床保健雜志, 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, 段家懷, 蔣小燕, 等. 阿托伐他汀對 T2DM 患者血清脂多糖及相關炎癥因子的影響. 湖南師范大學學報(醫學版), 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, 楊浩, 王燁. 腸道菌群代謝產物短鏈脂肪酸與 2 型糖尿病的關系. 新疆醫科大學學報, 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. 顧冠聰, 周懿憶, 陳華. 糖尿病周圍神經病變患者血清總膽汁酸和總膽紅素水平變化及其診斷價值分析. 檢驗醫學與臨床, 2022, 19(24): 3396-3400.
23. Wahlstr?m 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. Salga?o 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. 鮑哲, 楊升偉, 柯賽賽, 等. 益生元對 2 型糖尿病患者糖脂代謝的影響. 醫學信息, 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. 祁悅, 張杰. 中醫藥治療糖尿病周圍神經病變的臨床研究進展. 時珍國醫國藥, 2021, 32(2): 428-432.
40. 崔祥, 陶金華, 江曙, 等. 黃連提取物與腸道菌群的相互作用研究. 中草藥, 2018, 49(9): 2103-2107.
41. 張芹, 周中凱, 張惠媛. 蕎麥殼水提物調控糖尿病大鼠腸道菌群結構的研究. 中國糧油學報, 2017, 32(4): 31-36, 43.
42. 王文婷, 郭良清. 七味白術散通過調控腸道菌群改善 2 型糖尿病胰島素抵抗的理論探討. 西部中醫藥, 2022, 35(6): 56-59.

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