Application value of fecal microbiota transplantation for type 1 diabetes mellitus_West China Medical Journal

Authors：

LI Peilin ^1,2 , PAN Xiaoyan ² , YANG Chen ^2,3 , ZHAO Jing ^2,3 ,  DAI Xiaoyu ²

1. School of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Department of Nephrology, Mianyang Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;
3. School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P. R. China;

Corresponding author：

DAI Xiaoyu, Email: daixy001@163.com

Keywords：

Type 1 diabetes mellitus; fecal microbiota transplantation; treatment

DOI：

10.7507/1002-0179.202307177

Video：

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Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which pancreatic β cells are destroyed, resulting in an absolute lack of insulin. Intestinal microbiota and its metabolites can promote the progression of T1DM by destroying pancreatic β cells, increasing insulin resistance, increasing intestinal permeability, interfering with immune response. Therefore, fecal microbiota transplantation is expected to become a new method for preventing and treating T1DM in the future. This article mainly explores possible pathways for the application of fecal microbiota transplantation in T1DM, including protection of pancreatic β cells, improving insulin resistance, reducing intestinal permeability, and regulating immune responses.

Citation： LI Peilin, PAN Xiaoyan, YANG Chen, ZHAO Jing, DAI Xiaoyu. Application value of fecal microbiota transplantation for type 1 diabetes mellitus. West China Medical Journal, 2024, 39(1): 136-139. doi: 10.7507/1002-0179.202307177 Copy

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2.	Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract, 2022, 183: 109119.
3.	Piccioni A, Rosa F, Mannucci S, et al. Gut microbiota, LADA, and type 1 diabetes mellitus: an evolving relationship. Biomedicines, 2023, 11(3): 707.
4.	Robert S, Gysemans C, Takiishi T, et al. Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes, 2014, 63(8): 2876-2887.
5.	He L, Chen R, Zhang B, et al. Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus. Front Immunol, 2022, 13: 930872.
6.	de Groot P, Nikolic T, Pellegrini S, et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut, 2021, 70(1): 92-105.
7.	Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature, 2018, 562(7728): 589-594.
8.	Mariño E, Richards JL, McLeod KH, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol, 2017, 18(5): 552-562.
9.	Igudesman D, Crandell JL, Corbin KD, et al. Associations of dietary intake with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes and overweight or obesity. J Nutr, 2023, 153(4): 1178-1188.
10.	Wen L, Wong FS. Dietary short-chain fatty acids protect against type 1 diabetes. Nat Immunol, 2017, 18(5): 484-486.
11.	Sutherland AP, Van Belle T, Wurster AL, et al. Interleukin-21 is required for the development of type 1 diabetes in NOD mice. Diabetes, 2009, 58(5): 1144-1155.
12.	Ferreira RC, Simons HZ, Thompson WS, et al. IL-21 production by CD4⁺ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients. Diabetologia, 2015, 58(4): 781-790.
13.	Murri M, Leiva I, Gomez-Zumaquero JM, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med, 2013, 11: 46.
14.	Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J, 2011, 5(1): 82-91.
15.	Shi H, Kokoeva MV, Inouye K, et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest, 2006, 116(11): 3015-3025.
16.	de Kort S, Keszthelyi D, Masclee AA. Leaky gut and diabetes mellitus: what is the link?. Obes Rev, 2011, 12(6): 449-458.
17.	Hu S, Kuwabara R, de Haan BJ, et al. Acetate and butyrate improve β-cell metabolism and mitochondrial respiration under oxidative stress. Int J Mol Sci, 2020, 21(4): 1542.
18.	de Groot PF, Frissen MN, de Clercq NC, et al. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes, 2017, 8(3): 253-267.
19.	Ianiro G, Bibbò S, Porcari S, et al. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center. Gut Microbes, 2021, 13(1): 1994834.
20.	Le Roy T, Van der Smissen P, Paquot A, et al. Dysosmobacter welbionis gen. nov. , sp. nov. , isolated from human faeces and emended description of the genus Oscillibacter. Int J Syst Evol Microbiol, 2020, 70(9): 4851-4858.
21.	Le Roy T, Moens de Hase E, Van Hul M, et al. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut, 2022, 71(3): 534-543.
22.	Chambers ES, Byrne CS, Morrison DJ, et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut, 2019, 68(8): 1430-1438.
23.	Wu Z, Zhang B, Chen F, et al. Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: a randomized, controlled, prospective study. Front Cell Infect Microbiol, 2023, 12: 1089991.
24.	Paone P, Cani PD. Mucus barrier, mucins and gut microbiota: the expected slimy partners?. Gut, 2020, 69(12): 2232-2243.
25.	Förster C. Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol, 2008, 130(1): 55-70.
26.	Usuda H, Okamoto T, Wada K. Leaky gut: effect of dietary fiber and fats on microbiome and intestinal barrier. Int J Mol Sci, 2021, 22(14): 7613.
27.	Vaarala O. Leaking gut in type 1 diabetes. Curr Opin Gastroenterol, 2008, 24(6): 701-706.
28.	Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: a systematic review. Metabolism, 2017, 68: 133-144.
29.	Macfarlane GT, Macfarlane S. Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol, 2011(Suppl 45): S120-S127.
30.	Rastelli M, Knauf C, Cani PD. Gut microbes and health: a focus on the mechanisms linking microbes, obesity, and related disorders. Obesity (Silver Spring), 2018, 26(5): 792-800.
31.	Muradi A, Jasirwan COM, Simanjuntak CD, et al. The correlation of short-chain fatty acids with peripheral arterial disease in diabetes mellitus patients. Life (Basel), 2022, 12(10): 1464.
32.	Peng L, Li ZR, Green RS, et al. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr, 2009, 139(9): 1619-1625.
33.	Dedrick S, Sundaresh B, Huang Q, et al. The role of gut microbiota and environmental factors in type 1 diabetes pathogenesis. Front Endocrinol (Lausanne), 2020, 11: 78.
34.	Hand TW, Dos Santos LM, Bouladoux N, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science, 2012, 337(6101): 1553-1556.
35.	Guo S, Nighot M, Al-Sadi R, et al. Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR4 signal transduction pathway activation of FAK and MyD88. J Immunol, 2015, 195(10): 4999-5010.
36.	Nighot M, Al-Sadi R, Guo S, et al. Lipopolysaccharide-induced increase in intestinal epithelial tight permeability is mediated by toll-like receptor 4/myeloid differentiation primary response 88 (MyD88) activation of myosin light chain kinase expression. Am J Pathol, 2017, 187(12): 2698-2710.
37.	周迎, 李阳阳, 刘煜. 粪菌移植对非肥胖糖尿病小鼠发生 1 型糖尿病的影响及其机制探讨. 中华医学杂志, 2022, 102(16): 1224-1231.
38.	Cook L, Stahl M, Han X, et al. Suppressive and gut-reparative functions of human type 1 T regulatory cells. Gastroenterology, 2019, 157(6): 1584-1598.
39.	Scherm MG, Serr I, Zahm AM, et al. miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nat Commun, 2019, 10(1): 5697.
40.	Serr I, Fürst RW, Achenbach P, et al. Type 1 diabetes vaccine candidates promote human Foxp3(⁺)Treg induction in humanized mice. Nat Commun, 2016, 7: 10991.
41.	Steliou K, Boosalis MS, Perrine SP, et al. Butyrate histone deacetylase inhibitors. Biores Open Access, 2012, 1(4): 192-198.
42.	Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 2013, 504(7480): 451-455.
43.	Tanoue T, Atarashi K, Honda K. Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol, 2016, 16(5): 295-309.

1. Ruegsegger GN, Creo AL, Cortes TM, et al. Altered mitochondrial function in insulin-deficient and insulin-resistant states. J Clin Invest, 2018, 128(9): 3671-3681.
2. Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract, 2022, 183: 109119.
3. Piccioni A, Rosa F, Mannucci S, et al. Gut microbiota, LADA, and type 1 diabetes mellitus: an evolving relationship. Biomedicines, 2023, 11(3): 707.
4. Robert S, Gysemans C, Takiishi T, et al. Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes, 2014, 63(8): 2876-2887.
5. He L, Chen R, Zhang B, et al. Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus. Front Immunol, 2022, 13: 930872.
6. de Groot P, Nikolic T, Pellegrini S, et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut, 2021, 70(1): 92-105.
7. Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature, 2018, 562(7728): 589-594.
8. Mariño E, Richards JL, McLeod KH, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol, 2017, 18(5): 552-562.
9. Igudesman D, Crandell JL, Corbin KD, et al. Associations of dietary intake with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes and overweight or obesity. J Nutr, 2023, 153(4): 1178-1188.
10. Wen L, Wong FS. Dietary short-chain fatty acids protect against type 1 diabetes. Nat Immunol, 2017, 18(5): 484-486.
11. Sutherland AP, Van Belle T, Wurster AL, et al. Interleukin-21 is required for the development of type 1 diabetes in NOD mice. Diabetes, 2009, 58(5): 1144-1155.
12. Ferreira RC, Simons HZ, Thompson WS, et al. IL-21 production by CD4⁺ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients. Diabetologia, 2015, 58(4): 781-790.
13. Murri M, Leiva I, Gomez-Zumaquero JM, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med, 2013, 11: 46.
14. Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J, 2011, 5(1): 82-91.
15. Shi H, Kokoeva MV, Inouye K, et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest, 2006, 116(11): 3015-3025.
16. de Kort S, Keszthelyi D, Masclee AA. Leaky gut and diabetes mellitus: what is the link?. Obes Rev, 2011, 12(6): 449-458.
17. Hu S, Kuwabara R, de Haan BJ, et al. Acetate and butyrate improve β-cell metabolism and mitochondrial respiration under oxidative stress. Int J Mol Sci, 2020, 21(4): 1542.
18. de Groot PF, Frissen MN, de Clercq NC, et al. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes, 2017, 8(3): 253-267.
19. Ianiro G, Bibbò S, Porcari S, et al. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center. Gut Microbes, 2021, 13(1): 1994834.
20. Le Roy T, Van der Smissen P, Paquot A, et al. Dysosmobacter welbionis gen. nov. , sp. nov. , isolated from human faeces and emended description of the genus Oscillibacter. Int J Syst Evol Microbiol, 2020, 70(9): 4851-4858.
21. Le Roy T, Moens de Hase E, Van Hul M, et al. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut, 2022, 71(3): 534-543.
22. Chambers ES, Byrne CS, Morrison DJ, et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut, 2019, 68(8): 1430-1438.
23. Wu Z, Zhang B, Chen F, et al. Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: a randomized, controlled, prospective study. Front Cell Infect Microbiol, 2023, 12: 1089991.
24. Paone P, Cani PD. Mucus barrier, mucins and gut microbiota: the expected slimy partners?. Gut, 2020, 69(12): 2232-2243.
25. Förster C. Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol, 2008, 130(1): 55-70.
26. Usuda H, Okamoto T, Wada K. Leaky gut: effect of dietary fiber and fats on microbiome and intestinal barrier. Int J Mol Sci, 2021, 22(14): 7613.
27. Vaarala O. Leaking gut in type 1 diabetes. Curr Opin Gastroenterol, 2008, 24(6): 701-706.
28. Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: a systematic review. Metabolism, 2017, 68: 133-144.
29. Macfarlane GT, Macfarlane S. Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol, 2011(Suppl 45): S120-S127.
30. Rastelli M, Knauf C, Cani PD. Gut microbes and health: a focus on the mechanisms linking microbes, obesity, and related disorders. Obesity (Silver Spring), 2018, 26(5): 792-800.
31. Muradi A, Jasirwan COM, Simanjuntak CD, et al. The correlation of short-chain fatty acids with peripheral arterial disease in diabetes mellitus patients. Life (Basel), 2022, 12(10): 1464.
32. Peng L, Li ZR, Green RS, et al. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr, 2009, 139(9): 1619-1625.
33. Dedrick S, Sundaresh B, Huang Q, et al. The role of gut microbiota and environmental factors in type 1 diabetes pathogenesis. Front Endocrinol (Lausanne), 2020, 11: 78.
34. Hand TW, Dos Santos LM, Bouladoux N, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science, 2012, 337(6101): 1553-1556.
35. Guo S, Nighot M, Al-Sadi R, et al. Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR4 signal transduction pathway activation of FAK and MyD88. J Immunol, 2015, 195(10): 4999-5010.
36. Nighot M, Al-Sadi R, Guo S, et al. Lipopolysaccharide-induced increase in intestinal epithelial tight permeability is mediated by toll-like receptor 4/myeloid differentiation primary response 88 (MyD88) activation of myosin light chain kinase expression. Am J Pathol, 2017, 187(12): 2698-2710.
37. 周迎, 李阳阳, 刘煜. 粪菌移植对非肥胖糖尿病小鼠发生 1 型糖尿病的影响及其机制探讨. 中华医学杂志, 2022, 102(16): 1224-1231.
38. Cook L, Stahl M, Han X, et al. Suppressive and gut-reparative functions of human type 1 T regulatory cells. Gastroenterology, 2019, 157(6): 1584-1598.
39. Scherm MG, Serr I, Zahm AM, et al. miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nat Commun, 2019, 10(1): 5697.
40. Serr I, Fürst RW, Achenbach P, et al. Type 1 diabetes vaccine candidates promote human Foxp3(⁺)Treg induction in humanized mice. Nat Commun, 2016, 7: 10991.
41. Steliou K, Boosalis MS, Perrine SP, et al. Butyrate histone deacetylase inhibitors. Biores Open Access, 2012, 1(4): 192-198.
42. Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 2013, 504(7480): 451-455.
43. Tanoue T, Atarashi K, Honda K. Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol, 2016, 16(5): 295-309.

West China Medical Journal

Application value of fecal microbiota transplantation for type 1 diabetes mellitus

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