Tip 2 Diyabetin Mikrobiyal Yönü: Bağırsak Mikrobiyotasının Rolü ve Terapötik Potansiyeli
Year 2026,
Volume: 21 Issue: 1
,
219
-
233
,
30.03.2026
Aylin Çolak
,
Hüseyin Kahraman
,
Yusuf Ziya Çolak
Abstract
Diyabet ve obezite gibi metabolik hastalıklar, küresel ölçekte önemli halk sağlığı sorunları oluşturmaktadır. Bu rahatsızlıklar arasında diyabet, modern çağın en yaygın ve etkili hastalıklarından biri olarak öne çıkmaktadır. Giderek artan kanıtlar, diyabetin birçok yaşamı tehdit eden komplikasyonun gelişmesinde önemli bir etken olduğunu göstermektedir. Son zamanlarda, insan mikrobiyomu, Diyabet Mellitus'un patofizyolojisindeki rolü nedeniyle artan bir ilgi görmektedir. Yüksek verimli sekanslama teknolojilerindeki yenilikler, bağırsak mikrobiyotasının profillenmesini sağlayarak metabolik düzenlemedeki kritik rollerini ortaya koymuştur. Özellikle, bu mikrobiyal topluluklar glikoz ve lipid metabolizmasının yanı sıra yağ dokusu fonksiyonunu da modüle etmektedir. Birçok araştırma grubu, bağırsak mikrobiyotasını hedeflemenin diyabet yönetimi için yenilikçi tedavi yolları sağlayabileceğini öne sürmektedir. Bu derleme, bağırsak mikrobiyal bileşimi ile Tip 2 Diyabet Mellitus'un patogenezi arasındaki etkileşimi aydınlatmayı amaçlamaktadır.
References
-
Prawitt J. Caron S. Staels B. Bile acid metabolism and the pathogenesis of type 2 diabetes. Curr. Diabetes Rep. 2011; 11: 160- 166.
-
Maa Q. Lia Y. Lia P. Wang M. Wang J. Tang Z. Wang T. Luo L. et al. Research progress in the relationship between type 2 diabetes mellitus and intestinal flora Biomed. Pharmacother. 2019; 117: 109138.
-
Barrio C. Arias-Sánchez S. Martín-Monzón I. The gut microbiota-brain axis, psychobiotics, and impact on brain and behavior: a systematic review. Psychoneuroendocrinology 2022; 137: 105640.
-
Allin K.H. Nielsen T. Pedersen O. Gut microbiota in patients with type 2 diabetes mellitus. European Journal of Endocrinology 2015; 172: 167–177.
-
Tremaroli V. Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489(7415): 242-249.
-
Guarner F. Malagelada J.R. Gut flora in health and disease. Lancet 2003; 361(9356): 512-519.
-
Ley R.E. Turnbaugh P.J. Klein S. Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444(7122): 1022-1023.
-
Ley R.E. Beckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005; 102(31): 11070-11075.
-
Turnbaugh P.J. Ley R.E. Mahowald M.A. Magrini V. Mardis E.R. Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444(7122): 1027-1031.
-
Duncan S H. Lobley G.E. Holtrop G. Ince J. Johnstone A.M. Louis, P. Flint H.J. Human colonic microbiota associated with diet, obesity and weight loss. International Journal of Obesity 2008; 32(11): 1720-1724.
-
Leylabadlo H.E. Sanaieb S Heravie, F.S. Ahmadian Z. Ghotaslou R. From role of gut microbiota to microbial-based therapies in type 2-diabetes. Infect. Genet. Evol. 2020; 81: 104268.
-
Du L. Li Q. Yi H. Kuang T. Tang Y. Fan G. Gut microbiota-derived metabolites as key players in type 2 diabetes mellitus. Biomedicine & Pharmacotherapy 2022; 149: 112839.
-
Pan Y. Bu T. Deng X. Ji J. Yuan G. Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis. Endocrine 2024; 84: 1-15.
-
Torre L.E., Melián K. Moreno A. Alonso J. Sabatier C.A. Hernández M. Bermúdez L. Rodríguez B.L. Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World Journal of Gastroenterology 2009; 15(2): 204-210.
-
Harvey R.A. Ferrier D.R. Biochemistry. Lippincott Williams & Wilkins, Philadelphia. The United States of America, 2011.
-
Yousafzai M.U.R. Rehman M.U Dietary fibers and their effects on health. Res. Rev. Int. J. Multidiscip. 2021; 6: 35–42.
-
Zhao L. Zhang F. Ding X. Wu G. Lam Y.Y. Wang X. Fu H. Xue et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359(6380): 1151–1156.
-
Cai X. Yu H. Liu L. Lu T. Li J. Ji Y. Le Z. Bao et al. Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double Blind, Placebo-Controlled. Molecular Nutrition & Food Research 2018; 62: 1800865.
-
Partula V. Deschasaux M. Druesne-Pecollo N. Latino-Martel P. Desmetz E. Chazelas E. Kesse-Guyot E. Julia C. et al. Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective. Am. J. Clin. Nutr. 2020; 112: 195-207.
-
Kimura Y. Yoshida D. Hirakawa Y. Hat J. Honda T. Shibata M. Sakata S. Uchida K. et al. Dietary fiber intake and risk of type 2 diabetes in a general Japanese population: The Hisayama Study. Journal of Diabetes Investigation 2021; 12: 527-536.
-
Makki K. Deehan E. C. Walter J. Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 2018; 23: 705-715.
-
Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell 2016; 165: 1332-1345.
-
McCreight L.J. Bailey C.J. Pearson E.R. Metformin and the gastrointestinal tract. Diabetologia 2016; 59: 426-435.
-
Qin J. Li Y. Cai Z. Li S. Zhu J. Zhang F. Liang S. Zhang W. et al. A metagenomewide association study of gut microbiota in type 2 diabetes. Nature 2012; 490: 55.
-
Hamer H.M. Jonkers D. Venema K. Vanhoutvin S. Troost F.J. Brummer R.J. The role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics 2008; 27: 104-119.
-
Cao Y. Yao G. Sheng,Y. Yang L. Wang Z. Yang Z. Zhuang P. Zhang Y. JinQi Jiangtang tablet regulates gut microbiota and improve insulin sensitivity in type 2 diabetes mice. Journal of Diabetes Research 2019; 1872134.
-
Mandaliya D.K. Seshadri S. Short chain fatty acids, pancreatic dysfunction and type 2 diabetes. Pancreatology 2019; 19: 280-284.
-
Hirasawa A. Hara T. Katsuma S. Adachi T. Tsujimoto G. Free fatty acid receptors and drug discovery. Biological and Pharmaceutical Bulletin 2008; 31: 1847-1851.
-
Macia L. Thorburn A.N. Binge L.C. Marino E. Rogers K.E. Maslowski K.M. Vieira A.T. Kranich J. et al. Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol. Rev. 2012; 245: 164-176.
-
Liu L. Huh J.R. Shah K. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. EbioMedicine 2022; 77: 103908.
-
Hee B.V.D. Wells J.M. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol 2021; 29(8): 700-712.
-
Li X. Shimizu Y. Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci. Microbiota Food Health 2017; 36(4): 135-140.
-
Corrêa-Oliveira R. Fachi J.L. Vieira A. Sato F.T. Vinolo M.A.R. Regulation of immune cell function by short-chain fatty acids. Clinical & Translational Immunology 2016; 5(4): e73.
-
McNelis J.C. Lee Y.S. Mayoral R. Kant R.V.D. Johnson A.M.F. Wollam J. Olefsky J.M. GPR43 Potentiates β-Cell Function in Obesity. Diabetes 2015; 64(9): 3203-3217.
-
Veprik A. Laufer D. Weiss S. Rubins N. Walker M.D. GPR41 modulates insulin secretion and gene expression in pancreatic β-cells and modifies metabolic homeostasis in fed and fasting states. FASEB Journal 2016; 30(11): 3860-3869.
-
Thangaraju M. Cresci G.A. Liu K. Ananth S. Gnanaprakasam J.P. Browning D.D. Mellinger J.D. Smith S.B. et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Research 2009; 69(7): 2826-2832.
-
Xiong R.G. Zhou D.D. Wu S.X. Huang S.Y. Saimaiti A. Yang Z.J. Shang A. Zhao C.N. et al. Health benefits and side effects of short-chain fatty acids. Foods 2022; 11(18): 2863.
-
Canfora E.E. Jocken J.W. Blaak E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews Endocrinology 2015; 11(10): 577–591.
-
Jiang L. Gulanski B.I. Feyter H.M.D. Weinzimer S.A. Pittman B. Guidone E. Koretski J. Harman S. Petrakis I.L. Krystal J.H. Mason G.F. Increased brain uptake and oxidation of acetate in heavy drinkers. The Journal of Clinical Investigation 2013; 123(4): 1605-1614.
-
Frost G. Sleeth M.L. Sahuri-Arisoylu M. Lizarbe B. Cerdan S. Brody L. Anastasovska J. Ghourab et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications 2014; 5: 3611.
-
Psichas A. Sleeth M.L. Murphy K.G. Brooks L. Bewick G.A. Hanyaloglu A.C. Ghatei M.A. Bloom S.R. et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 2015; 39(3): 424-429.
-
Louis P. Flint H.J. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol. Lett. 2009; 294: 1-8.
-
Alexander C. Swanson K.S. Fahey G.C. Garleb K.A. Perspective: Physiologic Importance of Short-Chain Fatty Acids from Nondigestible Carbohydrate Fermentation. Advances in Nutrition 2019; 10(4): 576–589.
-
Pedersen S.S. Prause M. Sørensen C. Størling J. Moritz T. Mariño E. Billestrup N. Targeted Delivery of Butyrate Improves Glucose Homeostasis, Reduces Hepatic Lipid Accumulation and Inflammation in db/db Mice. Int. J. Mol. Sci. 2023; 24(5): 4533.
-
Wu H. Tremaroli V. Schmidt C. Lundqvist A. Olsson L.M. Krämer M. Gummesson A. Perkins R. et al. The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study. Cell Metabolism 2020; 32(3): 379-390.e3.
-
Ray K. Microbial metabolites feed into the gut–brain–gut circuit during host metabolism. Nature Reviews Gastroenterology & Hepatology 2014; 11(2): 76.
-
Hartstra A.V. Bouter K.E. Bäckhed F. Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 2015; 38: 159-165.
-
Gao Z. Yin J. Ward R.E. Martin R.J. Lefevre M. Cefalu W.T. Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009; 58: 1509-1517.
-
Karlsson F.H. Tremaroli V. Nookaew I. Bergström G. Behre C.J. Fagerberg B. Nielsen J. Bäckhed F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013; 498: 99-103.
-
Sato J. Kanazawa A. Ikeda F. Yoshihara T. Goto H. Abe H. Komiya K. Kawaguchi et al. Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 2014; 37: 2343-2350.
-
Texiera F.S. Grzeskowiak L.M. Salminen S. Laitinen K. Bressan J. Peluzio M.D.C.G. Faecal levels of Bifidobacterium and Clostridium coccoides but not plasma lipopolysaccharide are inversely related to insulin and HOMA index in women. Clinical Nutrition 2013; 32: 1017-1022.
-
Claesson M.J. Jeffery L.B. Conde S. Power S.E. O'Connor E.M. Cusack S. Harris H.M.B. Coakley M. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488: 178-184.
-
Sheflin A.M. Borresen E.C. Kirkwood J.S. Boot C.M. Whitney A.K. Lu S. Brown R.J. Broeckling C.D. et al. Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors. Molecular Nutrition & Food Research 2017; 61: 1500905.
-
Kopf J.C. Suhr M.J. Clarke J. Eyun S.I. Riethoven J.J.M. Ramer-Tait A.E. Rose D.J. Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: A randomized controlled trial. Nutrition Journal 2018; 17: 72.
-
Jang S.E. Kim K.A. Han M.J. Kim D.H. Doenjang, a fermented Korean soybean paste, inhibits lipopolysaccharide production of gut microbiota in mice. Journal of Medicinal Food 2014; 17: 67-75.
-
Jiang F. Du C. Jiang W. Wang L. Du S.K. The preparation, formation, fermentability, and applications of resistant starch. International Journal of Biological Macromolecules 2020; 150: 1155-1161.
-
Kim K.N. Yao Y. Ju S.Y. Short chain fatty acids and fecal microbiota abundance in humans with obesity: A systematic review and meta-analysis. Nutrients 2019; 11: 2512.
-
McLoughlin R.F. Berthon B.S. Jensen M.E. Baines K.J. Wood L.G. Short-chain fatty acids, prebiotics, synbiotics and systemic inflammation: A systematic review and meta-analysis. Am. J. Clin. Nutr. 2017; 106: 930-945.
-
Metzler-Zebeli B. Canibe N. Montagne L. Freire J. Bosi P. Prates J.A.M. Tanghe S. Trevisi P. Resistant starch reduces large intestinal pH and promotes fecal lactobacilli and bifidobacteria in pigs. Animal 2019; 13: 64-73.
-
Reichardt N. Duncan S.H. Young P. Belenguer A. Leitch C.M. Scott K.P. Flint H.J. Louis P. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. The ISME Journal 2014; 8: 1323-1335.
-
Vital M. Howe A.C. Tiedje J.M. Revealing the bacterial butyrate synthesis pathways by analyzing (meta) genomic data. Mbio 2014; 5: e00889-14.
-
Serpa J. Caiado F. Carvalho T. Torre C. Gonçalves L.G. Casalou C. Lamosa P. Rodrigues M. et al. Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells. The Journal of Biological Chemistry 2010; 285: 39211-39223.
-
Muhammad M. Yong Z. Likang Q. The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids. Foods 2023; 12: 1023.
-
Robertson M.D. Prebiotics and type 2 diabetes: Targeting the gut microbiota for improved glycaemic control?. Practical Diabetes 2020; 37: 133-137.
-
Jia L. Li D. Feng N. Shamoon M. Sun Z. Ding L. Zhang H. Chen W. et al. Anti-diabetic effects of Clostridium butyricum CGMCC0313.1 through promoting the growth of gut butyrate-producing bacteria in type 2 diabetic mice. Scientific Reports 2017; 7: 7046.
-
Patel S. Mandaliya D. Seshadri S. Colonic Microsphere modulated microflora and liver immunological response to diet induced diabetes in mice. Indian J. Microbiol. 2019; 19: 349-357.
-
Jena P.K. Singh S. Prajapati B. Nareshkumar G. Mehta T. Seshadri S. Impact of targeted specific antibiotic delivery for gut microbiota modulation on high-fructose-fed rats. Applied Biochemistry and Biotechnology 2014; 172: 3810-3826 .
-
Morrison D.J. Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016; 7: 189-200.
-
Fleming S. Fitch M. DeVries S. Liu M.L. Kight, C. Nutrient utilization by cells isolated from rat jejunum, cecum and colon. The Journal of Nutrition 1991; 121: 869-878.
-
Brown A.J. Goldsworthy S.M. Barnes A.A. Eilert M.M. Tcheang L. Daniels D. Muir A.I. Wigglesworth et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. The Journal of Biological Chemistry 2003; 278: 11312–11319.
-
Itoh Y. Kawamata Y. Harada M. Kobayashi M. Fujii R. Fukusumi S. Ogi K. Hosoya M. et al. Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature 2003; 422: 173-176.
-
Kristinsson H. Bergsten P. Sargsyan E. Free fatty acid receptor 1 (FFAR1/GPR40) signaling affects insulin secretion by enhancing mitochondrial respiration during palmitate exposure. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2015; 1853: 3248-3257.
-
Hirasawa A. Tsumaya K. Awaji T. Katsuma S. Adachi T. Yamada M. Sugimoto Y. Miyazaki S. et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nature Medicine 2005; 11: 90-94.
-
Lin H.V. Frassetto A. Kowalik Jr E.J. Nawrocki A.R. Lu M.M. Kosinski J.R. Hubert J.A. Szeto D. et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012; 7: e35240.
-
Guo Y. Xiao Z. Wang Y. Yao W. Liao S. Yu B. Zhang J. Zhang Y. et al. Sodium butyrate ameliorates streptozotocin-induced type 1 diabetes in mice by inhibiting the HMGB1 expression. Frontiers in Endocrinology 2018; 9: 630.
-
Xu Y. Wang N. Tan H.Y. Li S. Zhang C. Feng Y. Function of Akkermansia muciniphila in obesity: Interactions with lipid metabolism, immune response and gut systems. Front. Microbiol. 2020; 11: 219.
-
Huang K. Wang M.M. Kulinich A. Yao H.L. Ma H.Y. Martínez J.E R. Duan X.C. Chen H. et al. Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila. Carbohydrate Research 2015; 415: 60-65.
-
Ottman N. Huuskonen L. Reunanen J. Boeren S. Klievink J. Smidt H. Belzer C. Vos, W.M.D. Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front. Microbiol. 2016; 7: 1157.
-
Mandaliya D.K. Seshadri S. Short Chain Fatty Acids, pancreatic dysfunction and type 2 diabetes. Pancreatology 2019; 19: 617-622.
-
Pingitore A. Chambers E.S. Hill T. Maldonado I.R. Liu B. Bewick G. Morrison D.J. Preston T. et al. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes. Metab. 2017; 19: 257-265.
-
Sanna S. Zuydam N.R.V. Mahajan A. Kurilshikov A. Vila A.V. Võsa U. Mujagic Z. Masclee A.A M. et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics 2019; 51: 600-605.
-
Doumatey A.P. Adeyemo A. Zhou J. Lei L. Adebamowo S.N. Adebamowo C. Rotimi C.N. Gut Microbiome Profiles Are Associated With Type 2 Diabetes in Urban Africans. Frontiers in Cellular and Infection Microbiology 2020; 10: 63.
-
Fassatoui M. Lopez-Siles M. Díaz-Rizzolo D.A. Jmel H. Naouali C. Abdessalem G. Chikhaoui A. Nadal B. et al. Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus. Bioscience Reports 2019; 39.
-
Zhao L. Lou H. Peng Y. Chen S. Fan L. Li X. Elevated levels of circulating short-chain fatty acids and bile acids in type 2 diabetes are linked to gut barrier disruption and disordered gut microbiota. Diabetes Res. Clin. Pract. 2020; 169: 108418.
-
Roager H.M. Licht T.R. Microbial tryptophan catabolites in health and disease. Nature Communications 2018; 9: 1-10.
-
Elsden S.R. Hilton M.G. Wallr J.M. The end products of the metabolism of aromatic amino acids by Clostridia. Archives of Microbiology 1976; 107: 283-288.
-
Young S.N. Anderson G.M. Gauthier S. Purdy W.C. The origin of indoleacetic acid and indolepropionic acid in rat and human cerebrospinal fluid. J. Neurochem. 1980; 34(4): 1087–1092.
-
Wahlström A. Sayin S.I. Marschall H.U. Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metabolism 2016; 24: 41-50.
-
Thomas C. Gioiello A. Noriega L. Strehle A. Oury J. Rizzo G. Macchiarulo A. Yamamoto H. et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metabolism 2009; 10: 167-177.
-
Li R. Andreu-Sánchez S. Kuipers F. Fu J. Gut microbiome and bile acids in obesity-related diseases. Best Pract. Res. Clin. Endocrinol. Metab. 2021; 35(3): 101493.
-
Trabelsi M.S. Daoudi M. Prawitt J. Ducastel S. Touche V. Sayin S.I. Perino A. Brighton C.A. et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nature Communications 2015; 6: 7629.
-
Watanabe M. Houten S.M. Mataki C. Christoffolete M.A. Kim B.W. Sato H. Messaddeq N. Harney J.W. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439(7075): 484-489.
-
Chiang J.Y.L. Ferrell J.M. Bile Acids as Metabolic Regulators and Nutrient Sensors. Annual Review of Nutrition 2019; 39: 175-200.
-
Ryan K.K. Kohli R. Gutierrez-Aguilar R. Gaitonde S.G. Woods S.C. Seeley R.J. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endokrinoloji 2013; 154(1): 9-15.
-
Martin C.R. Osadchiy V. Kalani A. Mayer E.A. The Brain-Gut-Microbiome Axis, Cell. Mol. Gastroenterol. Hepatol. 2018; 6(2): 133-148.
-
Marcelin G. Jo Y.H. Li X. Schwartz G.J. Zhang Y. Dun N.J. Lyu R.M. Blouet C. et al. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol. Metab. 2014; 3(1): 19-28.
-
Pathak P. Xie C. Nichols R.G. Ferrell J.M. Boehme S. Krausz K.W. Patterson A.D. Gonzalez F.J. et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology 2018; 68(4): 1574-1588.
-
Tang W.W. Wang Z. Li X.S. Fan Y. Li D.S. Wu Y. Hazen S.L. Increased trimethylamine N-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clinical Chemistry 2017; 63: 297-306.
-
Zhuang R. Ge X. Han L. Yu P. Gong X. Meng Q. Zhang Y. Fan H et al. Gut microbe–generated metabolite trimethylamine N-oxide and the risk of diabetes: A systematic review and dose-response meta-analysis. Obes. Rev. 2019; 20(6): 883–894.
-
Gancheva S. Jelenik T. Álvarez-Hernández E. Roden M. Interorgan metabolic crosstalk in human insulin resistance. Physiological Reviews 2018; 98: 1371-1415.
-
Lynch C.J. Adams S.H. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat. Rev. Endocrinol. 2014; 10: 723.
-
Felig P. Marliss E. Cahill Jr G.F. Plasma amino acid levels and insulin secretion in obesity. The New England Journal of Medicine 1969; 281: 811-816.
-
Cheng S. Wiklund P. Autio R. Borra R. Ojanen X. Xu L. Törmäkangas T. Alen M. Adipose tissue dysfunction and altered systemic amino acid metabolism are associated with non-alcoholic fatty liver disease. Public Library of Science One 2015; 10: e0138889.
-
Bloomgarden Z. Diabetes and branched-chain amino acids: What is the link?. Journal of Diabetes 2018; 10: 350–352.
-
Collado M.C. Derrien M. Isolauri E. Vos W.M.D. Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Applied and Environmental Microbiology 2007; 73: 7767-7770.
-
Wang L. Christophersen C.T. Sorich M.J. Gerber J.P. Angley M.T. Conlon M.A. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Applied and Environmental Microbiology 2011; 77: 6718-6721.
-
Hansen C. Krych L. Nielsen D.S. Vogensen F.K. Hansen L.H. Sørensen S.J. Buschard K. Hansen A.K. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD Mouse. Diabetologia 2012; 55: 2285-2294.
-
Aron R.A.C. Abid A. Vesa C.M. Nechifor A.C. Behl T. Ghitea T.C. Munteanu M.A. Fratila O. et al. Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium. Microorganisms 2021; 9: 618.
-
Larsen N. Vogensen F.K. Berg F.W.J.V.D. Nielsen D.S. Andreasen A.S. Pedersen B.K. Al-Soud W.A. Sørensen S.J. et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. Public Library of Science One 2010; 5: e9085.
-
Vaarala O. Atkinson M.A. Neu J. The “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability and mucosal immunity. Diabetes 2008; 57: 2555-2562.
-
Membrez M. Blancher F. Jaquet M. Bibiloni R. Cani P.D. Burcelin R.G. Corthesy I. Macé K. et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 2008; 22: 2416-2426.
-
Diamant M. Blaak E. Vos W.D. Do nutrient–gut microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?. Obesity Reviews 2011; 12: 272-281.
-
Musso G. Gambino R. Cassader M. Obesity, diabetes and gut microbiota. Diabetes Care 2010; 33: 2277-2284.
-
Cani P.D. Bibiloni R. Knauf C. Waget A. Neyrinck A.M. Delzenne N.M. Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes 2008; 57(6): 1470–1481.
-
Cani P.D. Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Current Pharmaceutical Design 2009; 15(13): 1546–1558.
-
Smushkin G. Sathananthan M. Piccinini F. Man C.D. Law J.H. Cobelli C. Zinsmeister A.R. Rizza R.A. et al. The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes 2013; 62, 1094-1101.
-
Guo W. Zhang Z. Li L. Liang X. Wu Y. Wang X. Ma H. Cheng J. et al. Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes. Pharmacological Research 2022; 182: 106355.
-
Carrizales-Sánchez A.K. Tamez-Rivera O. Rodríguez-Gutiérrez N.A. Elizondo-Montemayor L. Gradilla-Hernández M.S. García-Rivas G. Pacheco A. Senés-Guerrero C. Characterization of gut microbiota associated with metabolic syndrome and type-2 diabetes mellitus in Mexican pediatric subjects. BMC Pediatrics 2023; 23: 210.
-
Cai L. Wu H. Li D. Zhou K. Zou F. Type 2 Diabetes Biomarkers of Human Gut Microbiota Selected via Iterative Sure Independent Screening Method. PLOS One 2015; 10(10): e0140827.
-
Du Y. Neng Q. Li Y. Kang Y. Guo L. Huang X. Chen M. Yang F. et al. Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus. Frontiers in Cellular and Infection Microbiology 2021; 11: 804733.
-
Esquivel-Hernández D.A. Martínez-López Y.E. Sánchez-Castañeda J.P. Neri-Rosario D. Padrón-Manrique C. Giron-Villalobos D. Mendoza-Ortíz C. Resendis-Antonio O. A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort. Frontiers in Endocrinology 2023; 14: 1128767.
-
Yatsunenko T. Rey F.E. Manary M.J. Trehan I. Dominguez-Bello M.G. Contreras M. Magris M. Hidalgo G. et al. Human gut microbiome viewed across age and geography. Nature 2012; 486(7402): 222–227.
-
Filippo C.D. Cavalieri D. Paola M.D. Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences 2010; 107(33): 14691-14696.
-
Ley R.E. Obesity and the human microbiome. Current Opinion in Gastroenterology 2010; 26(1): 5-11.
-
Rajilic-Stojanovic M. Biagi E. Heilig H.G.H.J. Kajander K. Kekkonen R.A. Tims S. Vos W.M.D. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141(5): 1792-1801.
-
Salamone D. Albarosa Rivellese A. Vetrani C. The relationship between gut microbiota, short chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre. Acta Diabetologica2021; 58: 1131-1138.
-
Liu S. Cao R. Liu L. Lv Y. Qi, X. Yuan Z. Fan X. Yu C. et al. Correlation Between Gut Microbiota and Testosterone in Male Patients With Type 2 Diabetes Mellitus. Front. Endocrinol. 2022; 13: 836485.
-
Slouha E. Rezazadah A. Farahbod K. Gerts A. Clunes L.A. Kollias T.F. Type-2 Diabetes Mellitus and the Gut Microbiota: Systematic Review. Cureus 2022; 15(11): e49740.
-
Zhang X. Shen D. Fang Z. Jie Z. Qiu X. Zhang C. Chen Y. Ji L. Human gut microbiota changes reveal the progression of glucose intolerance. PLOS ONE 2013; 8(8): e71108.
-
Qiu J. Zhou H. Jing Y. Dong C. Association between blood microbiome and type 2 diabetes mellitus: a nested case-control study. J. Clin. Lab. Anal. 2019; 33(4): e22842.
-
Wu X. Ma C. Han L. Nawaz M. Gao F. Zhang X. Xu P. Zhang J. et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Current Microbiology 2011; 62(2): 169-178.
-
Lê K.A. Li Y. Xu X. Yang W. Liu T. Zhao X. Tang Y.G. Cai D. et al. Alterations in fecal Lactobacillus and Bifidobacterium species in type 2 diabetic patients in Southern China population. Frontiers in Physiology 2012; 3: 496.
-
Wellen K.E. Hotamisligil G.S. Inflammation, stress, and diabetes. The Journal of Clinical Investigation 2005; 115: 1111-1119.
-
Everard A. Cani P.D. Diabetes, obesity and gut microbiota. Best Practice & Research Clinical Gastroenterology 2013; 27: 73-83.
-
Devaraj S. Hemarajata P. Versalovic J.The human gut microbiome and body metabolism: implications for obesity and diabetes. Clinical Chemistry 2013; 59: 617-628.
-
Gerritsen J. Smidt H. Rijkers G.T. Vos W.M.D. Intestinal microbiota in human health and disease: the impact of probiotics. Genes & Nutrition 2011; 6: 209-240.
-
Cani P. Rottier O. Goiot Y. Neyrinck A. Geurts L. Changes in Gut Microbiota Control Intestinal Permeability-induced Inflammation in Obese and Diabetic Mice through Unexpected Dependent Mechanisms. Diabetologia 2008; 57: 1470–1481.
-
Cani P.D. Possemiers S. Wiele T.V.D. Guiot Y. Everard A. Rottier O. Geurts L. Naslain D. et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58: 1091–1103.
-
Singh S. Sharma R.K. Malhotra S. Pothuraju R. Shandilya U.K. Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocin-treated rats. Beneficial Microbes 2017; 8(2): 243-255.
-
Zhao L. Lou H. Peng Y. Chen S. Zhang Y. Li X. Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications. Endocrine 2019; 66: 526–537.
-
Tuomainen M. Lindström J. Lehtonen M. Auriola S. Pihlajamäki J. Peltonen M. Tuomilehto J. Uusitupa M. et al. Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutrition & Diabetes 2018; 8: 35.
-
Vangipurapu J. Fernandes Silva L. Kuulasmaa T. Smith U. Laakso M. Microbiota-related metabolites and the risk of type 2 diabetes. Diabetes Care 2020; 43: 1319-1325.
The Microbial Face of Type 2 Diabetes: The Role of Gut Microbiota and Therapeutic Potential
Year 2026,
Volume: 21 Issue: 1
,
219
-
233
,
30.03.2026
Aylin Çolak
,
Hüseyin Kahraman
,
Yusuf Ziya Çolak
Abstract
Metabolic diseases, such as diabetes and obesity, constitute significant public health challenges on a global scale. Among these conditions, diabetes emerges as one of the most widespread and impactful diseases of the modern era. Accumulating evidence shows that diabetes is major contributing factor to the development of several life-threatening complications. Recently, the human microbiome has garnered increased attention for its role in the pathophysiology of Diabetes Mellitus. Innovations in high-throughput sequencing technologies have enabled profiling of the gut microbiota, revealing their critical roles in metabolic regulation. Specifically, these microbial communities are implicated in modulating glucose and lipid metabolism, as well as adipose tissue function. Many research groups suggest that targeting the gut microbiota may provide inovatife therapeutic avenues for diabetes management. This review aims to elucidate the interplay between gut microbial composition and the pathogenesis of Type 2 Diabetes Mellitus.
References
-
Prawitt J. Caron S. Staels B. Bile acid metabolism and the pathogenesis of type 2 diabetes. Curr. Diabetes Rep. 2011; 11: 160- 166.
-
Maa Q. Lia Y. Lia P. Wang M. Wang J. Tang Z. Wang T. Luo L. et al. Research progress in the relationship between type 2 diabetes mellitus and intestinal flora Biomed. Pharmacother. 2019; 117: 109138.
-
Barrio C. Arias-Sánchez S. Martín-Monzón I. The gut microbiota-brain axis, psychobiotics, and impact on brain and behavior: a systematic review. Psychoneuroendocrinology 2022; 137: 105640.
-
Allin K.H. Nielsen T. Pedersen O. Gut microbiota in patients with type 2 diabetes mellitus. European Journal of Endocrinology 2015; 172: 167–177.
-
Tremaroli V. Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489(7415): 242-249.
-
Guarner F. Malagelada J.R. Gut flora in health and disease. Lancet 2003; 361(9356): 512-519.
-
Ley R.E. Turnbaugh P.J. Klein S. Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444(7122): 1022-1023.
-
Ley R.E. Beckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005; 102(31): 11070-11075.
-
Turnbaugh P.J. Ley R.E. Mahowald M.A. Magrini V. Mardis E.R. Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444(7122): 1027-1031.
-
Duncan S H. Lobley G.E. Holtrop G. Ince J. Johnstone A.M. Louis, P. Flint H.J. Human colonic microbiota associated with diet, obesity and weight loss. International Journal of Obesity 2008; 32(11): 1720-1724.
-
Leylabadlo H.E. Sanaieb S Heravie, F.S. Ahmadian Z. Ghotaslou R. From role of gut microbiota to microbial-based therapies in type 2-diabetes. Infect. Genet. Evol. 2020; 81: 104268.
-
Du L. Li Q. Yi H. Kuang T. Tang Y. Fan G. Gut microbiota-derived metabolites as key players in type 2 diabetes mellitus. Biomedicine & Pharmacotherapy 2022; 149: 112839.
-
Pan Y. Bu T. Deng X. Ji J. Yuan G. Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis. Endocrine 2024; 84: 1-15.
-
Torre L.E., Melián K. Moreno A. Alonso J. Sabatier C.A. Hernández M. Bermúdez L. Rodríguez B.L. Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World Journal of Gastroenterology 2009; 15(2): 204-210.
-
Harvey R.A. Ferrier D.R. Biochemistry. Lippincott Williams & Wilkins, Philadelphia. The United States of America, 2011.
-
Yousafzai M.U.R. Rehman M.U Dietary fibers and their effects on health. Res. Rev. Int. J. Multidiscip. 2021; 6: 35–42.
-
Zhao L. Zhang F. Ding X. Wu G. Lam Y.Y. Wang X. Fu H. Xue et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359(6380): 1151–1156.
-
Cai X. Yu H. Liu L. Lu T. Li J. Ji Y. Le Z. Bao et al. Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double Blind, Placebo-Controlled. Molecular Nutrition & Food Research 2018; 62: 1800865.
-
Partula V. Deschasaux M. Druesne-Pecollo N. Latino-Martel P. Desmetz E. Chazelas E. Kesse-Guyot E. Julia C. et al. Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective. Am. J. Clin. Nutr. 2020; 112: 195-207.
-
Kimura Y. Yoshida D. Hirakawa Y. Hat J. Honda T. Shibata M. Sakata S. Uchida K. et al. Dietary fiber intake and risk of type 2 diabetes in a general Japanese population: The Hisayama Study. Journal of Diabetes Investigation 2021; 12: 527-536.
-
Makki K. Deehan E. C. Walter J. Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 2018; 23: 705-715.
-
Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell 2016; 165: 1332-1345.
-
McCreight L.J. Bailey C.J. Pearson E.R. Metformin and the gastrointestinal tract. Diabetologia 2016; 59: 426-435.
-
Qin J. Li Y. Cai Z. Li S. Zhu J. Zhang F. Liang S. Zhang W. et al. A metagenomewide association study of gut microbiota in type 2 diabetes. Nature 2012; 490: 55.
-
Hamer H.M. Jonkers D. Venema K. Vanhoutvin S. Troost F.J. Brummer R.J. The role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics 2008; 27: 104-119.
-
Cao Y. Yao G. Sheng,Y. Yang L. Wang Z. Yang Z. Zhuang P. Zhang Y. JinQi Jiangtang tablet regulates gut microbiota and improve insulin sensitivity in type 2 diabetes mice. Journal of Diabetes Research 2019; 1872134.
-
Mandaliya D.K. Seshadri S. Short chain fatty acids, pancreatic dysfunction and type 2 diabetes. Pancreatology 2019; 19: 280-284.
-
Hirasawa A. Hara T. Katsuma S. Adachi T. Tsujimoto G. Free fatty acid receptors and drug discovery. Biological and Pharmaceutical Bulletin 2008; 31: 1847-1851.
-
Macia L. Thorburn A.N. Binge L.C. Marino E. Rogers K.E. Maslowski K.M. Vieira A.T. Kranich J. et al. Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol. Rev. 2012; 245: 164-176.
-
Liu L. Huh J.R. Shah K. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. EbioMedicine 2022; 77: 103908.
-
Hee B.V.D. Wells J.M. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol 2021; 29(8): 700-712.
-
Li X. Shimizu Y. Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci. Microbiota Food Health 2017; 36(4): 135-140.
-
Corrêa-Oliveira R. Fachi J.L. Vieira A. Sato F.T. Vinolo M.A.R. Regulation of immune cell function by short-chain fatty acids. Clinical & Translational Immunology 2016; 5(4): e73.
-
McNelis J.C. Lee Y.S. Mayoral R. Kant R.V.D. Johnson A.M.F. Wollam J. Olefsky J.M. GPR43 Potentiates β-Cell Function in Obesity. Diabetes 2015; 64(9): 3203-3217.
-
Veprik A. Laufer D. Weiss S. Rubins N. Walker M.D. GPR41 modulates insulin secretion and gene expression in pancreatic β-cells and modifies metabolic homeostasis in fed and fasting states. FASEB Journal 2016; 30(11): 3860-3869.
-
Thangaraju M. Cresci G.A. Liu K. Ananth S. Gnanaprakasam J.P. Browning D.D. Mellinger J.D. Smith S.B. et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Research 2009; 69(7): 2826-2832.
-
Xiong R.G. Zhou D.D. Wu S.X. Huang S.Y. Saimaiti A. Yang Z.J. Shang A. Zhao C.N. et al. Health benefits and side effects of short-chain fatty acids. Foods 2022; 11(18): 2863.
-
Canfora E.E. Jocken J.W. Blaak E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews Endocrinology 2015; 11(10): 577–591.
-
Jiang L. Gulanski B.I. Feyter H.M.D. Weinzimer S.A. Pittman B. Guidone E. Koretski J. Harman S. Petrakis I.L. Krystal J.H. Mason G.F. Increased brain uptake and oxidation of acetate in heavy drinkers. The Journal of Clinical Investigation 2013; 123(4): 1605-1614.
-
Frost G. Sleeth M.L. Sahuri-Arisoylu M. Lizarbe B. Cerdan S. Brody L. Anastasovska J. Ghourab et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications 2014; 5: 3611.
-
Psichas A. Sleeth M.L. Murphy K.G. Brooks L. Bewick G.A. Hanyaloglu A.C. Ghatei M.A. Bloom S.R. et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 2015; 39(3): 424-429.
-
Louis P. Flint H.J. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol. Lett. 2009; 294: 1-8.
-
Alexander C. Swanson K.S. Fahey G.C. Garleb K.A. Perspective: Physiologic Importance of Short-Chain Fatty Acids from Nondigestible Carbohydrate Fermentation. Advances in Nutrition 2019; 10(4): 576–589.
-
Pedersen S.S. Prause M. Sørensen C. Størling J. Moritz T. Mariño E. Billestrup N. Targeted Delivery of Butyrate Improves Glucose Homeostasis, Reduces Hepatic Lipid Accumulation and Inflammation in db/db Mice. Int. J. Mol. Sci. 2023; 24(5): 4533.
-
Wu H. Tremaroli V. Schmidt C. Lundqvist A. Olsson L.M. Krämer M. Gummesson A. Perkins R. et al. The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study. Cell Metabolism 2020; 32(3): 379-390.e3.
-
Ray K. Microbial metabolites feed into the gut–brain–gut circuit during host metabolism. Nature Reviews Gastroenterology & Hepatology 2014; 11(2): 76.
-
Hartstra A.V. Bouter K.E. Bäckhed F. Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 2015; 38: 159-165.
-
Gao Z. Yin J. Ward R.E. Martin R.J. Lefevre M. Cefalu W.T. Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009; 58: 1509-1517.
-
Karlsson F.H. Tremaroli V. Nookaew I. Bergström G. Behre C.J. Fagerberg B. Nielsen J. Bäckhed F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013; 498: 99-103.
-
Sato J. Kanazawa A. Ikeda F. Yoshihara T. Goto H. Abe H. Komiya K. Kawaguchi et al. Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 2014; 37: 2343-2350.
-
Texiera F.S. Grzeskowiak L.M. Salminen S. Laitinen K. Bressan J. Peluzio M.D.C.G. Faecal levels of Bifidobacterium and Clostridium coccoides but not plasma lipopolysaccharide are inversely related to insulin and HOMA index in women. Clinical Nutrition 2013; 32: 1017-1022.
-
Claesson M.J. Jeffery L.B. Conde S. Power S.E. O'Connor E.M. Cusack S. Harris H.M.B. Coakley M. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488: 178-184.
-
Sheflin A.M. Borresen E.C. Kirkwood J.S. Boot C.M. Whitney A.K. Lu S. Brown R.J. Broeckling C.D. et al. Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors. Molecular Nutrition & Food Research 2017; 61: 1500905.
-
Kopf J.C. Suhr M.J. Clarke J. Eyun S.I. Riethoven J.J.M. Ramer-Tait A.E. Rose D.J. Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: A randomized controlled trial. Nutrition Journal 2018; 17: 72.
-
Jang S.E. Kim K.A. Han M.J. Kim D.H. Doenjang, a fermented Korean soybean paste, inhibits lipopolysaccharide production of gut microbiota in mice. Journal of Medicinal Food 2014; 17: 67-75.
-
Jiang F. Du C. Jiang W. Wang L. Du S.K. The preparation, formation, fermentability, and applications of resistant starch. International Journal of Biological Macromolecules 2020; 150: 1155-1161.
-
Kim K.N. Yao Y. Ju S.Y. Short chain fatty acids and fecal microbiota abundance in humans with obesity: A systematic review and meta-analysis. Nutrients 2019; 11: 2512.
-
McLoughlin R.F. Berthon B.S. Jensen M.E. Baines K.J. Wood L.G. Short-chain fatty acids, prebiotics, synbiotics and systemic inflammation: A systematic review and meta-analysis. Am. J. Clin. Nutr. 2017; 106: 930-945.
-
Metzler-Zebeli B. Canibe N. Montagne L. Freire J. Bosi P. Prates J.A.M. Tanghe S. Trevisi P. Resistant starch reduces large intestinal pH and promotes fecal lactobacilli and bifidobacteria in pigs. Animal 2019; 13: 64-73.
-
Reichardt N. Duncan S.H. Young P. Belenguer A. Leitch C.M. Scott K.P. Flint H.J. Louis P. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. The ISME Journal 2014; 8: 1323-1335.
-
Vital M. Howe A.C. Tiedje J.M. Revealing the bacterial butyrate synthesis pathways by analyzing (meta) genomic data. Mbio 2014; 5: e00889-14.
-
Serpa J. Caiado F. Carvalho T. Torre C. Gonçalves L.G. Casalou C. Lamosa P. Rodrigues M. et al. Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells. The Journal of Biological Chemistry 2010; 285: 39211-39223.
-
Muhammad M. Yong Z. Likang Q. The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids. Foods 2023; 12: 1023.
-
Robertson M.D. Prebiotics and type 2 diabetes: Targeting the gut microbiota for improved glycaemic control?. Practical Diabetes 2020; 37: 133-137.
-
Jia L. Li D. Feng N. Shamoon M. Sun Z. Ding L. Zhang H. Chen W. et al. Anti-diabetic effects of Clostridium butyricum CGMCC0313.1 through promoting the growth of gut butyrate-producing bacteria in type 2 diabetic mice. Scientific Reports 2017; 7: 7046.
-
Patel S. Mandaliya D. Seshadri S. Colonic Microsphere modulated microflora and liver immunological response to diet induced diabetes in mice. Indian J. Microbiol. 2019; 19: 349-357.
-
Jena P.K. Singh S. Prajapati B. Nareshkumar G. Mehta T. Seshadri S. Impact of targeted specific antibiotic delivery for gut microbiota modulation on high-fructose-fed rats. Applied Biochemistry and Biotechnology 2014; 172: 3810-3826 .
-
Morrison D.J. Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016; 7: 189-200.
-
Fleming S. Fitch M. DeVries S. Liu M.L. Kight, C. Nutrient utilization by cells isolated from rat jejunum, cecum and colon. The Journal of Nutrition 1991; 121: 869-878.
-
Brown A.J. Goldsworthy S.M. Barnes A.A. Eilert M.M. Tcheang L. Daniels D. Muir A.I. Wigglesworth et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. The Journal of Biological Chemistry 2003; 278: 11312–11319.
-
Itoh Y. Kawamata Y. Harada M. Kobayashi M. Fujii R. Fukusumi S. Ogi K. Hosoya M. et al. Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature 2003; 422: 173-176.
-
Kristinsson H. Bergsten P. Sargsyan E. Free fatty acid receptor 1 (FFAR1/GPR40) signaling affects insulin secretion by enhancing mitochondrial respiration during palmitate exposure. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2015; 1853: 3248-3257.
-
Hirasawa A. Tsumaya K. Awaji T. Katsuma S. Adachi T. Yamada M. Sugimoto Y. Miyazaki S. et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nature Medicine 2005; 11: 90-94.
-
Lin H.V. Frassetto A. Kowalik Jr E.J. Nawrocki A.R. Lu M.M. Kosinski J.R. Hubert J.A. Szeto D. et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012; 7: e35240.
-
Guo Y. Xiao Z. Wang Y. Yao W. Liao S. Yu B. Zhang J. Zhang Y. et al. Sodium butyrate ameliorates streptozotocin-induced type 1 diabetes in mice by inhibiting the HMGB1 expression. Frontiers in Endocrinology 2018; 9: 630.
-
Xu Y. Wang N. Tan H.Y. Li S. Zhang C. Feng Y. Function of Akkermansia muciniphila in obesity: Interactions with lipid metabolism, immune response and gut systems. Front. Microbiol. 2020; 11: 219.
-
Huang K. Wang M.M. Kulinich A. Yao H.L. Ma H.Y. Martínez J.E R. Duan X.C. Chen H. et al. Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila. Carbohydrate Research 2015; 415: 60-65.
-
Ottman N. Huuskonen L. Reunanen J. Boeren S. Klievink J. Smidt H. Belzer C. Vos, W.M.D. Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front. Microbiol. 2016; 7: 1157.
-
Mandaliya D.K. Seshadri S. Short Chain Fatty Acids, pancreatic dysfunction and type 2 diabetes. Pancreatology 2019; 19: 617-622.
-
Pingitore A. Chambers E.S. Hill T. Maldonado I.R. Liu B. Bewick G. Morrison D.J. Preston T. et al. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes. Metab. 2017; 19: 257-265.
-
Sanna S. Zuydam N.R.V. Mahajan A. Kurilshikov A. Vila A.V. Võsa U. Mujagic Z. Masclee A.A M. et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics 2019; 51: 600-605.
-
Doumatey A.P. Adeyemo A. Zhou J. Lei L. Adebamowo S.N. Adebamowo C. Rotimi C.N. Gut Microbiome Profiles Are Associated With Type 2 Diabetes in Urban Africans. Frontiers in Cellular and Infection Microbiology 2020; 10: 63.
-
Fassatoui M. Lopez-Siles M. Díaz-Rizzolo D.A. Jmel H. Naouali C. Abdessalem G. Chikhaoui A. Nadal B. et al. Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus. Bioscience Reports 2019; 39.
-
Zhao L. Lou H. Peng Y. Chen S. Fan L. Li X. Elevated levels of circulating short-chain fatty acids and bile acids in type 2 diabetes are linked to gut barrier disruption and disordered gut microbiota. Diabetes Res. Clin. Pract. 2020; 169: 108418.
-
Roager H.M. Licht T.R. Microbial tryptophan catabolites in health and disease. Nature Communications 2018; 9: 1-10.
-
Elsden S.R. Hilton M.G. Wallr J.M. The end products of the metabolism of aromatic amino acids by Clostridia. Archives of Microbiology 1976; 107: 283-288.
-
Young S.N. Anderson G.M. Gauthier S. Purdy W.C. The origin of indoleacetic acid and indolepropionic acid in rat and human cerebrospinal fluid. J. Neurochem. 1980; 34(4): 1087–1092.
-
Wahlström A. Sayin S.I. Marschall H.U. Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metabolism 2016; 24: 41-50.
-
Thomas C. Gioiello A. Noriega L. Strehle A. Oury J. Rizzo G. Macchiarulo A. Yamamoto H. et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metabolism 2009; 10: 167-177.
-
Li R. Andreu-Sánchez S. Kuipers F. Fu J. Gut microbiome and bile acids in obesity-related diseases. Best Pract. Res. Clin. Endocrinol. Metab. 2021; 35(3): 101493.
-
Trabelsi M.S. Daoudi M. Prawitt J. Ducastel S. Touche V. Sayin S.I. Perino A. Brighton C.A. et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nature Communications 2015; 6: 7629.
-
Watanabe M. Houten S.M. Mataki C. Christoffolete M.A. Kim B.W. Sato H. Messaddeq N. Harney J.W. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439(7075): 484-489.
-
Chiang J.Y.L. Ferrell J.M. Bile Acids as Metabolic Regulators and Nutrient Sensors. Annual Review of Nutrition 2019; 39: 175-200.
-
Ryan K.K. Kohli R. Gutierrez-Aguilar R. Gaitonde S.G. Woods S.C. Seeley R.J. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endokrinoloji 2013; 154(1): 9-15.
-
Martin C.R. Osadchiy V. Kalani A. Mayer E.A. The Brain-Gut-Microbiome Axis, Cell. Mol. Gastroenterol. Hepatol. 2018; 6(2): 133-148.
-
Marcelin G. Jo Y.H. Li X. Schwartz G.J. Zhang Y. Dun N.J. Lyu R.M. Blouet C. et al. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol. Metab. 2014; 3(1): 19-28.
-
Pathak P. Xie C. Nichols R.G. Ferrell J.M. Boehme S. Krausz K.W. Patterson A.D. Gonzalez F.J. et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology 2018; 68(4): 1574-1588.
-
Tang W.W. Wang Z. Li X.S. Fan Y. Li D.S. Wu Y. Hazen S.L. Increased trimethylamine N-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clinical Chemistry 2017; 63: 297-306.
-
Zhuang R. Ge X. Han L. Yu P. Gong X. Meng Q. Zhang Y. Fan H et al. Gut microbe–generated metabolite trimethylamine N-oxide and the risk of diabetes: A systematic review and dose-response meta-analysis. Obes. Rev. 2019; 20(6): 883–894.
-
Gancheva S. Jelenik T. Álvarez-Hernández E. Roden M. Interorgan metabolic crosstalk in human insulin resistance. Physiological Reviews 2018; 98: 1371-1415.
-
Lynch C.J. Adams S.H. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat. Rev. Endocrinol. 2014; 10: 723.
-
Felig P. Marliss E. Cahill Jr G.F. Plasma amino acid levels and insulin secretion in obesity. The New England Journal of Medicine 1969; 281: 811-816.
-
Cheng S. Wiklund P. Autio R. Borra R. Ojanen X. Xu L. Törmäkangas T. Alen M. Adipose tissue dysfunction and altered systemic amino acid metabolism are associated with non-alcoholic fatty liver disease. Public Library of Science One 2015; 10: e0138889.
-
Bloomgarden Z. Diabetes and branched-chain amino acids: What is the link?. Journal of Diabetes 2018; 10: 350–352.
-
Collado M.C. Derrien M. Isolauri E. Vos W.M.D. Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Applied and Environmental Microbiology 2007; 73: 7767-7770.
-
Wang L. Christophersen C.T. Sorich M.J. Gerber J.P. Angley M.T. Conlon M.A. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Applied and Environmental Microbiology 2011; 77: 6718-6721.
-
Hansen C. Krych L. Nielsen D.S. Vogensen F.K. Hansen L.H. Sørensen S.J. Buschard K. Hansen A.K. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD Mouse. Diabetologia 2012; 55: 2285-2294.
-
Aron R.A.C. Abid A. Vesa C.M. Nechifor A.C. Behl T. Ghitea T.C. Munteanu M.A. Fratila O. et al. Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium. Microorganisms 2021; 9: 618.
-
Larsen N. Vogensen F.K. Berg F.W.J.V.D. Nielsen D.S. Andreasen A.S. Pedersen B.K. Al-Soud W.A. Sørensen S.J. et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. Public Library of Science One 2010; 5: e9085.
-
Vaarala O. Atkinson M.A. Neu J. The “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability and mucosal immunity. Diabetes 2008; 57: 2555-2562.
-
Membrez M. Blancher F. Jaquet M. Bibiloni R. Cani P.D. Burcelin R.G. Corthesy I. Macé K. et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 2008; 22: 2416-2426.
-
Diamant M. Blaak E. Vos W.D. Do nutrient–gut microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?. Obesity Reviews 2011; 12: 272-281.
-
Musso G. Gambino R. Cassader M. Obesity, diabetes and gut microbiota. Diabetes Care 2010; 33: 2277-2284.
-
Cani P.D. Bibiloni R. Knauf C. Waget A. Neyrinck A.M. Delzenne N.M. Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes 2008; 57(6): 1470–1481.
-
Cani P.D. Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Current Pharmaceutical Design 2009; 15(13): 1546–1558.
-
Smushkin G. Sathananthan M. Piccinini F. Man C.D. Law J.H. Cobelli C. Zinsmeister A.R. Rizza R.A. et al. The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes 2013; 62, 1094-1101.
-
Guo W. Zhang Z. Li L. Liang X. Wu Y. Wang X. Ma H. Cheng J. et al. Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes. Pharmacological Research 2022; 182: 106355.
-
Carrizales-Sánchez A.K. Tamez-Rivera O. Rodríguez-Gutiérrez N.A. Elizondo-Montemayor L. Gradilla-Hernández M.S. García-Rivas G. Pacheco A. Senés-Guerrero C. Characterization of gut microbiota associated with metabolic syndrome and type-2 diabetes mellitus in Mexican pediatric subjects. BMC Pediatrics 2023; 23: 210.
-
Cai L. Wu H. Li D. Zhou K. Zou F. Type 2 Diabetes Biomarkers of Human Gut Microbiota Selected via Iterative Sure Independent Screening Method. PLOS One 2015; 10(10): e0140827.
-
Du Y. Neng Q. Li Y. Kang Y. Guo L. Huang X. Chen M. Yang F. et al. Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus. Frontiers in Cellular and Infection Microbiology 2021; 11: 804733.
-
Esquivel-Hernández D.A. Martínez-López Y.E. Sánchez-Castañeda J.P. Neri-Rosario D. Padrón-Manrique C. Giron-Villalobos D. Mendoza-Ortíz C. Resendis-Antonio O. A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort. Frontiers in Endocrinology 2023; 14: 1128767.
-
Yatsunenko T. Rey F.E. Manary M.J. Trehan I. Dominguez-Bello M.G. Contreras M. Magris M. Hidalgo G. et al. Human gut microbiome viewed across age and geography. Nature 2012; 486(7402): 222–227.
-
Filippo C.D. Cavalieri D. Paola M.D. Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences 2010; 107(33): 14691-14696.
-
Ley R.E. Obesity and the human microbiome. Current Opinion in Gastroenterology 2010; 26(1): 5-11.
-
Rajilic-Stojanovic M. Biagi E. Heilig H.G.H.J. Kajander K. Kekkonen R.A. Tims S. Vos W.M.D. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141(5): 1792-1801.
-
Salamone D. Albarosa Rivellese A. Vetrani C. The relationship between gut microbiota, short chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre. Acta Diabetologica2021; 58: 1131-1138.
-
Liu S. Cao R. Liu L. Lv Y. Qi, X. Yuan Z. Fan X. Yu C. et al. Correlation Between Gut Microbiota and Testosterone in Male Patients With Type 2 Diabetes Mellitus. Front. Endocrinol. 2022; 13: 836485.
-
Slouha E. Rezazadah A. Farahbod K. Gerts A. Clunes L.A. Kollias T.F. Type-2 Diabetes Mellitus and the Gut Microbiota: Systematic Review. Cureus 2022; 15(11): e49740.
-
Zhang X. Shen D. Fang Z. Jie Z. Qiu X. Zhang C. Chen Y. Ji L. Human gut microbiota changes reveal the progression of glucose intolerance. PLOS ONE 2013; 8(8): e71108.
-
Qiu J. Zhou H. Jing Y. Dong C. Association between blood microbiome and type 2 diabetes mellitus: a nested case-control study. J. Clin. Lab. Anal. 2019; 33(4): e22842.
-
Wu X. Ma C. Han L. Nawaz M. Gao F. Zhang X. Xu P. Zhang J. et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Current Microbiology 2011; 62(2): 169-178.
-
Lê K.A. Li Y. Xu X. Yang W. Liu T. Zhao X. Tang Y.G. Cai D. et al. Alterations in fecal Lactobacillus and Bifidobacterium species in type 2 diabetic patients in Southern China population. Frontiers in Physiology 2012; 3: 496.
-
Wellen K.E. Hotamisligil G.S. Inflammation, stress, and diabetes. The Journal of Clinical Investigation 2005; 115: 1111-1119.
-
Everard A. Cani P.D. Diabetes, obesity and gut microbiota. Best Practice & Research Clinical Gastroenterology 2013; 27: 73-83.
-
Devaraj S. Hemarajata P. Versalovic J.The human gut microbiome and body metabolism: implications for obesity and diabetes. Clinical Chemistry 2013; 59: 617-628.
-
Gerritsen J. Smidt H. Rijkers G.T. Vos W.M.D. Intestinal microbiota in human health and disease: the impact of probiotics. Genes & Nutrition 2011; 6: 209-240.
-
Cani P. Rottier O. Goiot Y. Neyrinck A. Geurts L. Changes in Gut Microbiota Control Intestinal Permeability-induced Inflammation in Obese and Diabetic Mice through Unexpected Dependent Mechanisms. Diabetologia 2008; 57: 1470–1481.
-
Cani P.D. Possemiers S. Wiele T.V.D. Guiot Y. Everard A. Rottier O. Geurts L. Naslain D. et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58: 1091–1103.
-
Singh S. Sharma R.K. Malhotra S. Pothuraju R. Shandilya U.K. Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocin-treated rats. Beneficial Microbes 2017; 8(2): 243-255.
-
Zhao L. Lou H. Peng Y. Chen S. Zhang Y. Li X. Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications. Endocrine 2019; 66: 526–537.
-
Tuomainen M. Lindström J. Lehtonen M. Auriola S. Pihlajamäki J. Peltonen M. Tuomilehto J. Uusitupa M. et al. Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutrition & Diabetes 2018; 8: 35.
-
Vangipurapu J. Fernandes Silva L. Kuulasmaa T. Smith U. Laakso M. Microbiota-related metabolites and the risk of type 2 diabetes. Diabetes Care 2020; 43: 1319-1325.