Gut Microbiome and Diabetes: Emerging Perspectives in Metabolic Regulation

Navreet  Kaur; Navjot Kaur; Aanchal  Verma; Rahul Kumar Sharma

doi:10.5937/scriptamed57-61236

Navreet Kaur Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial college of pharmacy (An Autonomous College) BELA (Ropar) Punjab-140111
Navjot Kaur Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial college of pharmacy (An Autonomous College) BELA (Ropar) Punjab-140111
Aanchal Verma Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial college of pharmacy (An Autonomous College) BELA (Ropar) Punjab-140111
Rahul Kumar Sharma Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial COLLEGE OF PHARMACY (An Autonomous College) BELA (Ropar) Pb. 140 111

DOI: https://doi.org/10.5937/scriptamed57-61236

Sažetak

Diabetes mellitus Type 2 (T2DM) is one of the fastest-growing metabolic disorders in the world. It is marked by insulin resistance, high blood sugar and high cholesterol levels. Recently, its prevalence has increased significantly, making it a major health issue globally. New evidence shows that people with T2DM often have changes in their gut microbiota composition and suffer from problems in multiple organ systems. This review focused on the changes in gut microbiota related to T2DM and examines how microbial byproducts affect the disease's development. The potential for identifying at-risk individuals based on microbial patterns and the creation of specific treatments was also discussed. Lastly, it was looked into gut health strategies that aim to change the gut microbiota to prevent or slow the advancement of T2DM.

Reference

References

Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65. doi: 10.1038/NATURE08821.

Faith JJ, Colombel JF, Gordon JI. Identifying strains that contribute to complex diseases through the study of microbial inheritance. Proc Natl Acad Sci U S A. 2015;112:633-40. doi: 10.1073/PNAS.1418781112.

Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, et al. Human genetics shape the gut microbiome. Cell. 2014;159:789-99. doi: 10.1016/J.CELL.2014.09.053.

Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22:713-22. doi: 10.1038/NM.4142.

Beydag-Tasöz BS, Yennek S, Grapin-Botton A. Towards a better understanding of diabetes mellitus using organoid models. Nat Rev Endocrinol. 2023;19:232-48. doi: 10.1038/S41574-022-00797-X.

Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes. 2017;66:241-55. doi: 10.2337/DB16-0806.

Reynolds AN, Akerman AP, Mann J. Dietary fibre and whole grains in diabetes management: systematic review and meta-analyses. PLoS Med. 2020;17:e1003053. doi: 10.1371/JOURNAL.PMED.1003053.

Ojo O, Wang X, Ojo OO, Brooke J, Jiang Y, Dong Q, et al. The effect of prebiotics and oral anti-diabetic agents on gut microbiome in patients with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Nutrients. 2022;14. doi: 10.3390/NU14235139.

Gülden E, Wong FS, Wen L. The gut microbiota and type 1 diabetes. Clin Immunol. 2015;159:143-53. doi: 10.1016/J.CLIM.2015.05.013.

Craciun CI, Neag MA, Catinean A, Mitre AO, Rusu A, Bala C, et al. The relationships between gut microbiota and diabetes mellitus, and treatments for diabetes mellitus. Biomedicines. 2022;10:308. doi: 10.3390/BIOMEDICINES10020308.

Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23:469-80. doi: 10.1111/J.1464-5491.2006.01858.X.

Upadhyaya S, Banerjee G. Type 2 diabetes and gut microbiome: at the intersection of known and unknown. Gut Microbes. 2015;6:85-92. doi: 10.1080/19490976.2015.1024918.

Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54:2325-40. doi: 10.1194/JLR.R036012.

Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3. doi: 10.4161/GMIC.19897.

Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174-80. doi: 10.1038/NATURE09944.

Alam C, Bittoun E, Bhagwat D, Valkonen S, Saari A, Jaakkola U, et al. Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia. 2011;54:1398-406. doi: 10.1007/S00125-011-2097-5.

Paun A, Yau C, Danska JS. The influence of the microbiome on type 1 diabetes. J Immunol. 2017;198:590-5. doi: 10.4049/JIMMUNOL.1601519.

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474:327-36. doi: 10.1038/NATURE10213.

Mason KL, Huffnagle GB, Noverr MC, Kao JY. Overview of gut immunology. Adv Exp Med Biol. 2008;635:1-14. doi: 10.1007/978-0-387-09550-9_1.

Wen L, Duffy A. Factors influencing the gut microbiota, inflammation, and type 2 diabetes. J Nutr. 2017;147:1468S-1475S. doi: 10.3945/JN.116.240754.

Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009;32 Suppl 2. doi: 10.2337/DC09-S301.

Jaacks LM, Vandevijvere S, Pan A, McGowan CJ, Wallace C, Imamura F, et al. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019;7:231-40. doi: 10.1016/S2213-8587(19)30026-9.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84. doi: 10.1002/HEP.28431.

Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375:2369-79. doi: 10.1056/NEJMRA1600266.

Olofsson LE, Bäckhed F. The metabolic role and therapeutic potential of the microbiome. Endocr Rev. 2022;43:907-26. doi: 10.1210/ENDREV/BNAC004.

Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355-9. doi: 10.1126/SCIENCE.1124234.

Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BAH, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535:376-81. doi: 10.1038/NATURE18646.

Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359:1151-6. doi: 10.1126/SCIENCE.AAO5774.

Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 2016;8. doi: 10.1186/S13073-016-0303-2.

Chobot A, Górowska-Kowolik K, Sokołowska M, Jarosz-Chobot P. Obesity and diabetes—not only a simple link between two epidemics. Diabetes Metab Res Rev. 2018;34. doi: 10.1002/DMRR.3042.

Peters BA, Shapiro JA, Church TR, Miller G, Trinh-Shevrin C, Yuen E, et al. A taxonomic signature of obesity in a large study of American adults. Sci Rep. 2018;8:1-13. doi: 10.1038/s41598-018-28126-1.

Cani PD. Human gut microbiome: hopes, threats and promises. Gut. 2018;67:1716-25. doi: 10.1136/GUTJNL-2018-316723.

Singer-Englar T, Barlow G, Mathur R. Obesity, diabetes, and the gut microbiome: an updated review. Expert Rev Gastroenterol Hepatol. 2019;13:3-15. doi: 10.1080/17474124.2019.1543023.

Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541-6. doi: 10.1038/NATURE12506.

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85-97. doi: 10.1038/NRI2921.

Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341. doi: 10.1126/SCIENCE.1241214.

Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498:99-103. doi: 10.1038/NATURE12198.

Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26:611-619.e6. doi: 10.1016/J.CMET.2017.09.008.

Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8. doi: 10.1371/JOURNAL.PONE.0071108.

Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213-23. doi: 10.1016/J.CHOM.2008.02.015.

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027-31. doi: 10.1038/NATURE05414.

Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022-3. doi: 10.1038/4441022A.

Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049-57. doi: 10.2337/DB10-0253.

Morotomi M, Nagai F, Watanabe Y. Description of Christensenella minuta gen. nov., sp. nov., isolated from human faeces, which forms a distinct branch in the order Clostridiales, and proposal of Christensenellaceae fam. nov. Int J Syst Evol Microbiol. 2011;62:144-9. doi: 10.1099/IJS.0.026989-0/CITE/REFWORKS.

Beaumont M, Goodrich JK, Jackson MA, Yet I, Davenport ER, Vieira-Silva S, et al. Heritable components of the human fecal microbiome are associated with visceral fat. Genome Biol. 2016;17. doi: 10.1186/S13059-016-1052-7.

Konikoff T, Gophna U. Oscillospira: a central, enigmatic component of the human gut microbiota. Trends Microbiol. 2016;24:523-4. doi: 10.1016/J.TIM.2016.02.015.

Liu R, Hong J, Xu X, Feng Q, Zhang D, Gu Y, et al. Gut microbiome and serum metabolome alterations in obesity and after weight loss intervention. Nat Med. 2017;23:859-68. doi: 10.1038/nm.4358.

Daousi C, Casson IF, Gill GV, MacFarlane IA, Wilding JPH, Pinkney JH. Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors. Postgrad Med J. 2006;82:280-4. doi: 10.1136/PMJ.2005.039032.

Jia W, Xie G, Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018;15:111-28. doi: 10.1038/NRGASTRO.2017.119.

Chiang JYL, Ferrell JM. Bile acids as metabolic regulators and nutrient sensors. Annu Rev Nutr. 2019;39:175-200. doi: 10.1146/ANNUREV-NUTR-082018-124344.

Wahlström A, Sayin SI, Marschall HU, Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24:41-50. doi: 10.1016/J.CMET.2016.05.005.

Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 2015;22:971-82. doi: 10.1016/J.CMET.2015.10.001.

Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116:1102-9. doi: 10.1172/JCI25604.

Prawitt J, Abdelkarim M, Stroeve JHM, Popescu I, Duez H, Velagapudi VR, et al. Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes. 2011;60:1861-71. doi: 10.2337/DB11-0030.

Potthoff MJ, Kliewer SA, Mangelsdorf DJ. Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev. 2012;26:312-24. doi: 10.1101/GAD.184788.111.

Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell. 2000;6:507-15. doi: 10.1016/S1097-2765(00)00050-2.

Duran-Sandoval D, Mautino G, Martin G, Percevault F, Barbier O, Fruchart JC, et al. Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes. 2004;53:890-8. doi: 10.2337/DIABETES.53.4.890.

Caron S, Huaman Samanez C, Dehondt H, Ploton M, Briand O, Lien F, et al. Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol Cell Biol. 2013;33:2202-11. doi: 10.1128/MCB.01004-12.

Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun. 2015;6. doi: 10.1038/NCOMMS8629.

Popescu IR, Helleboid-Chapman A, Lucas A, Vandewalle B, Dumont J, Bouchaert E, et al. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS Lett. 2010;584:2845-51. doi: 10.1016/J.FEBSLET.2010.04.068.

Düfer M, Hörth K, Wagner R, Schittenhelm B, Prowald S, Wagner TFJ, et al. Bile acids acutely stimulate insulin secretion of mouse β cells via farnesoid X receptor activation and KATP channel inhibition. Diabetes. 2012;61:1479-89. doi: 10.2337/DB11-0815/-/DC1.

Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018;24:1919-29. doi: 10.1038/S41591-018-0222-4.

Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145. doi: 10.1053/J.GASTRO.2013.05.042.

Steiner C, Othman A, Saely CH, Rein P, Drexel H, von Eckardstein A, et al. Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus. PLoS One. 2011;6. doi: 10.1371/JOURNAL.PONE.0025006.

Parséus A, Sommer N, Sommer F, Caesar R, Molinaro A, Stahlman M, et al. Microbiota-induced obesity requires farnesoid X receptor. Gut. 2017;66:429-37. doi: 10.1136/GUTJNL-2015-310283.

Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189-200. doi: 10.1080/19490976.2015.1134082.

Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12:661-72. doi: 10.1038/NRMICRO3344.

Scott KP, Martin JC, Campbell G, Mayer CD, Flint HJ. Whole-genome transcription profiling reveals genes up-regulated by growth on fucose in the human gut bacterium “Roseburia inulinivorans.” J Bacteriol. 2006;188:4340-9. doi: 10.1128/JB.00137-06.

Rey FE, Faith JJ, Bain J, Muehlbauer MJ, Stevens RD, Newgard CB, et al. Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem. 2010;285:22082-90. doi: 10.1074/JBC.M110.117713.

Gaggini M, Carli F, Rosso C, Buzzigoli E, Marietti M, Della Latta V, et al. Altered amino acid concentrations in NAFLD: impact of obesity and insulin resistance. Hepatology. 2018;67:145-58. doi: 10.1002/HEP.29465.

Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311-26. doi: 10.1016/J.CMET.2009.02.002.

Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, et al. The adverse metabolic effects of branched chain amino acids are mediated by isoleucine and valine. Cell Metab. 2021;33:905-22.e6. doi: 10.1016/J.CMET.2021.03.025.

Würtz P, Tiainen M, Makinen VP, Kangas AJ, Soininen P, Saltevo J, et al. Circulating metabolite predictors of glycemia in middle aged men and women. Diabetes Care. 2012;35:1749-56. doi: 10.2337/DC11-1838.

Wurtz P, Soininen P, Kangas AJ, Rönnemaa T, Lehtimäki T, Kähönen M, et al. Branched chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care. 2013;36:648-55. doi: 10.2337/DC12-0895.

Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ, Higginbottom SK, et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature. 2017;551:648-52. doi: 10.1038/NATURE24661.

He K, Du S, Xun P, Sharma S, Wang H, Zhai F, et al. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS). Am J Clin Nutr. 2011;93:1328-36. doi: 10.3945/AJCN.110.008870.

Yoo W, Zieba JK, Foegeding NJ, Torres TP, Shelton CD, Shealy NG, et al. High fat diet induced colonocyte dysfunction escalates microbiota derived trimethylamine N oxide. Science. 2021;373:813-8. doi: 10.1126/SCIENCE.ABA3683.

Hoyles L, Jiménez Pranteda ML, Chilloux J, Brial F, Myridakis A, Aranias T, et al. Metabolic retroconversion of trimethylamine N oxide and the gut microbiota. Microbiome. 2018;6:73. doi: 10.1186/S40168-018-0461-0.

Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, et al. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology. Nat Commun. 2020;11. doi: 10.1038/S41467-020-19589-W.

De Mello VD, Paananen J, Lindström J, Lankinen MA, Shi L, Kuusisto J, et al. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci Rep. 2017;7. doi: 10.1038/SREP46337.

Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506-14. doi: 10.1038/NRGASTRO.2014.66.

Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol. 2019;16:605-16. doi: 10.1038/S41575-019-0173-3.

Won G, Choi SI, Kang CH, Kim GH. Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 ameliorates insulin resistance in palmitic acid induced HepG2 cells and high fat diet induced mice. Microorganisms. 2021;9. doi: 10.3390/MICROORGANISMS9061139.

Zhao S, Liu W, Wang J, Shi J, Sun Y, Wang W, et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet fed mice. J Mol Endocrinol. 2017;58:1-14. doi: 10.1530/JME-16-0054.

Zmora N, Zilberman Schapira G, Suez J, Mor U, Dori Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 2018;174:1388-1405.e21. doi: 10.1016/J.CELL.2018.08.041.

Suez J, Zmora N, Zilberman Schapira G, Mor U, Dori Bachash M, Bashiardes S, et al. Post antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174:1406-1423.e16. doi: 10.1016/J.CELL.2018.08.047.

Wang Y, Dilidaxi D, Wu Y, Sailike J, Sun X, Nabi XH. Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP 1 secretion in db/db mice. Biomed Pharmacother. 2020;125. doi: 10.1016/J.BIOPHA.2020.109914.

Tonucci LB, Olbrich dos Santos KM, Licursi de Oliveira L, Rocha Ribeiro SM, Duarte Martino HS. Clinical application of probiotics in type 2 diabetes mellitus: a randomized, double blind, placebo controlled study. Clin Nutr. 2017;36:85-92. doi: 10.1016/J.CLNU.2015.11.011.

Rittiphairoj T, Pongpirul K, Janchot K, Mueller NT, Li T. Probiotics contribute to glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta analysis. Adv Nutr. 2021;12:722-34. doi: 10.1093/ADVANCES/NMAA133.

Tao YW, Gu YL, Mao XQ, Zhang L, Pei YF. Effects of probiotics on type II diabetes mellitus: a meta analysis. J Transl Med. 2020;18. doi: 10.1186/S12967-020-02213-2.

Kocsis T, Molnár B, Németh D, Hegyi P, Szakács Z, Bálint A, et al. Probiotics have beneficial metabolic effects in patients with type 2 diabetes mellitus: a meta analysis of randomized clinical trials. Sci Rep. 2020;10. doi: 10.1038/S41598-020-68440-1.

Waisundara VY, Siu SY, Hsu A, Huang D, Tan BKH. Baicalin upregulates the genetic expression of antioxidant enzymes in Type 2 diabetic Goto Kakizaki rats. Life Sci. 2011;88:1016-25. doi: 10.1016/J.LFS.2011.03.009.

Zhao L, Ma P, Peng Y, Wang M, Peng C, Zhang Y, et al. Amelioration of hyperglycaemia and hyperlipidaemia by adjusting the interplay between gut microbiota and bile acid metabolism: Radix Scutellariae as a case. Phytomedicine. 2021;83. doi: 10.1016/J.PHYMED.2021.153477.

Zhang Y, Xu Y, Zhang L, Chen Y, Wu T, Liu R, et al. Licorice extract ameliorates hyperglycemia through reshaping gut microbiota structure and inhibiting TLR4/NF κB signaling pathway in type 2 diabetic mice. Food Res Int. 2022;153:110945. doi: 10.1016/J.FOODRES.2022.110945.

Zhang C, Sheng J, Sarsaiya S, Shu F, Liu T, Tu X, et al. The anti diabetic activities, gut microbiota composition, the anti inflammatory effects of Scutellaria–coptis herb couple against insulin resistance model of diabetes involving the toll like receptor 4 signaling pathway. J Ethnopharmacol. 2019;237:202-14. doi: 10.1016/J.JEP.2019.02.040.

Li XW, Chen HP, He YY, Chen WL, Chen JW, Gao L, et al. Effects of rich polyphenols extract of Dendrobium loddigesii on anti diabetic, anti inflammatory, anti oxidant, and gut microbiota modulation in db/db mice. Molecules. 2018;23:3245. doi: 10.3390/MOLECULES23123245.

Xu X, Gao Z, Yang F, Yang Y, Chen L, Han L, et al. Antidiabetic effects of Gegen Qinlian Decoction via the gut microbiota are attributable to its key ingredient berberine. Genomics Proteomics Bioinformatics. 2020;18:721-36. doi: 10.1016/J.GPB.2019.09.007.

Habtemariam S. Berberine pharmacology and the gut microbiota: a hidden therapeutic link. Pharmacol Res. 2020;155. doi: 10.1016/J.PHRS.2020.104722.

Huang J, Guan B, Lin L, Wang Y. Improvement of intestinal barrier function, gut microbiota, and metabolic endotoxemia in type 2 diabetes rats by curcumin. Bioeng (Basel). 2021;12:11947-58. doi: 10.1080/21655979.2021.2009322.

Gao Y, Li J, Wang J, Li X, Li J, Chu S, et al. Ginsenoside Rg1 prevent and treat inflammatory diseases: a review. Int Immunopharmacol. 2020;87. doi: 10.1016/J.INTIMP.2020.106805.

Wei Y, Yang H, Zhu C, Deng J, Fan D. Hypoglycemic effect of ginsenoside Rg5 mediated partly by modulating gut microbiota dysbiosis in diabetic db/db mice. J Agric Food Chem. 2020;68:5107-17. doi: 10.1021/ACS.JAFC.0C00605.

Zeng SL, Li SZ, Xiao PT, Cai YY, Chu C, Chen BZ, et al. Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism. Sci Adv. 2020;6. doi: 10.1126/SCIADV.AAX6208.

Yang X, Dong B, An L, Zhang Q, Chen Y, Wang H, et al. Ginsenoside Rb1 ameliorates glycemic disorder in mice with high fat diet induced obesity via regulating gut microbiota and amino acid metabolism. Front Pharmacol. 2021;12. doi: 10.3389/FPHAR.2021.756491.

Magkos F, Hjorth MF, Astrup A. Diet and exercise in the prevention and treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16:545-55. doi: 10.1038/S41574-020-0381-5.

O'Keefe SJ. The association between dietary fibre deficiency and high income lifestyle associated diseases: Burkitt’s hypothesis revisited. Lancet Gastroenterol Hepatol. 2019;4:984-96. doi: 10.1016/S2468-1253(19)30257-2.

David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559-63. doi: 10.1038/NATURE12820.

O'Grady J, O'Connor EM, Shanahan F. Review article: dietary fibre in the era of microbiome science. Aliment Pharmacol Ther. 2019;49:506-15. doi: 10.1111/APT.15129.

Ojo O, Feng QQ, Ojo OO, Wang XH. The role of dietary fibre in modulating gut microbiota dysbiosis in patients with type 2 diabetes: a systematic review and meta analysis of randomised controlled trials. Nutrients. 2020;12:1-21. doi: 10.3390/NU12113239.

Ojo O, Wang XH, Ojo OO, Adegboye ARA. The effects of almonds on gut microbiota, glycometabolism, and inflammatory markers in patients with type 2 diabetes: a systematic review and meta analysis of randomised controlled trials. Nutrients. 2021;13. doi: 10.3390/NU13103377.

Rinott E, Meir AY, Tsaban G, Zelicha H, Kaplan A, Knights D, et al. The effects of the green Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. Genome Med. 2022;14. doi: 10.1186/S13073-022-01015-Z.

Zaharieva DP, McGaugh S, Davis EA, Riddell MC. Advances in exercise, physical activity, and diabetes. Diabetes Technol Ther. 2020;22:S109-18. doi: 10.1089/DIA.2020.2508.

Clarke SF, Murphy EF, O’Sullivan O, Lucey AJ, Humphreys M, Hogan A, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63:1913-20. doi: 10.1136/GUTJNL-2013-306541.

Yang L, Lin H, Lin W, Xu X. Exercise ameliorates insulin resistance of type 2 diabetes through motivating short chain fatty acid mediated skeletal muscle cell autophagy. Biology (Basel). 2020;9. doi: 10.3390/BIOLOGY9080203.

Valder S, Brinkmann C. Exercise for the diabetic gut—potential health effects and underlying mechanisms. Nutrients. 2022;14. doi: 10.3390/NU14040813.

Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018;50:747-57. doi: 10.1249/MSS.0000000000001495.

O’Sullivan O, Cronin O, Clarke SF, Murphy EF, Molloy MG, Shanahan F, et al. Exercise and the microbiota. Gut Microbes. 2015;6:131-6. doi: 10.1080/19490976.2015.1011875.

Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242-9. doi: 10.1038/NATURE11552.

Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med. 2011;62:361-80. doi: 10.1146/ANNUREV-MED-012510-175505.

De Groot PF, Belzer C, Aydin Ö, Levin E, Levels JH, Aalvink S, et al. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PLoS One. 2017;12. doi: 10.1371/JOURNAL.PONE.0188475.

De Vadder F, Kovatcheva Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, et al. Microbiota generated metabolites promote metabolic benefits via gut brain neural circuits. Cell. 2014;156:84-96. doi: 10.1016/J.CELL.2013.12.016.

Völzke H, Alte D, Schmidt CO, Radke D, Lorbeer R, Friedrich N, et al. Cohort profile: the Study of Health in Pomerania. Int J Epidemiol. 2011;40:294-307. doi: 10.1093/IJE/DYP394.

Liu L, Zhang J, Cheng Y, Zhu M, Xiao Z, Ruan G, et al. Gut microbiota: a new target for T2DM prevention and treatment. Front Endocrinol (Lausanne). 2022;13. doi: 10.3389/FENDO.2022.958218.