A diabetes és előállapota − a praediabetes − prevalenciája világszerte exponenciális mértékben emelkedik. Mind több adat támasztja alá a bélmikrobiomnak a kórforma kialakulásában játszott szerepét. Jól ismert, hogy a pre-, a pro- és az ezek kombinációjából álló szinbiotikumok befolyásolhatják a bélflóra összetételét, s így szerepük lehet a diabeteshez vezető patogenetikai folyamatok megváltoztatásában, lassításában. Azt is mind több megfigyelés támasztja alá, hogy különböző gyógyszerek − köztük kiemelkedő jelentőséggel az antidiabetikumok − módosíthatják a mikrobiom összetételét. Munkánk irodalmi adatok alapján áttekinti a pre-, pro- és szinbiotikumok szénhidrát- és lipidanyagcserét befolyásoló hatását, valamint az 1-es és a 2-es típusú diabetes patogenezisét potenciálisan befolyásoló szerepét, emellett röviden kitér az antidiabetikumok bélflórát befolyásoló természetére is. Orv Hetil. 2024; 165(21): 803–812.
The prevalence of diabetes and its precursor state – the prediabetes – is exponentially spreading worldwide. More and more data suggest the role of gut microbiome in the pathogenesis of the aforementioned conditions. It is well known that pre-, probiotics, and their combination called synbiotics may influence the composition of the gut microflora. Thus they may play a key role in the progression or retardation of the pathogenetic process of diabetes. It is also supported by more and more observations that different drugs – in particular the antidiabetic drugs − can modify the composition of the microbiome. Based on literary data, the authors review the influencing effects of pre-, pro-, and synbiotics on the carbohydrate and lipid metabolism, as well as their potential role in the pathogenesis of type 1 and type 2 diabetes, and summarize briefly the role of antidiabetic drugs on the gut microbiome composition. Orv Hetil. 2024; 165(21): 803–812.
Crudele L, Gadaleta RM, Cariello M, et al. Gut microbiota in the pathogenesis and therapeutic approaches of diabetes. Lancet eBioMedicine 2023; 97: 104821.
Manilla V, Santopaolo F, Gasbarrini A, et al. Type 2 diabetes mellitus and liver disease: across the gut–liver axis from fibrosis to cancer. Nutrients 2023; 15: 2521.
Tomasics Gy, Schandl L, Polyák A, et al. Diabetes mellitus and the intestinal microbiome. [A diabetes mellitus és a bélmikrobiom.] Orv Hetil. 2023; 164: 981–987. [Hungarian]
Iatcu CO, Steen A, Covasa M. Gut microbiota and complications of type-2 diabetes. Nutrients 2022; 14: 166.
Gomes AC, Bueno AA, de Souza RG, et al. Gut microbiota, probiotics and diabetes. Nutr J. 2014; 13: 60.
Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods 2019; 8: 92.
Shigwedha N, Hiwilepo-Van Haal P, Jia L, et al. Prebiotics: metabolism and symbiotic synergy with probiotics in promoting health. Chapter 3. In: Rao V, Rao LG. (eds.) Probiotics and prebiotics in human nutrition and health. IntechOpen, Rijeka, 2016; pp. 41–57.
Senés-Guerrero C, Gradilla-Hernández M, García-Gamboa R, et al. Dietary fiber and gut microbiota. In: Welti-Chanes J, Serna-Saldivar SO, Campanella S, et al. (eds.) Science and technology of fibers in food systems. Springer Nature, Cham, 2020; pp. 277–298. e-ISBN: 978-3-030-38654-2.
Turck D, Castenmiller J, De Henauw S, et al. Beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood-glucose rise after consumption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J 2021; 19: e06493.
Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017; 14: 491–502.
Vinderola G, Sanders MA, Salminen S, et al. Postbiotics: the comcept and their use in healthy populations. Front Nutr. 2022; 9: 10002213.
Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics – a review. J Food Sci Technol. 2015; 52: 7577–7587.
Mansuy-Aubert V, Ravussin Y. Short chain fatty acids: the messengers from down below. Front Neurosci. 2023; 17: 1197759.
Pintarič M, Langerholc T. Probiotic mechanisms affecting glucose homeostasis: a scoping review. Life 2022; 12: 1187.
Song X, Liu Y, Zhang X, et al. Role of intestinal probiotics in the modulation of lipid metabolism: implications for therapeutic treatments. Food Sci Human Wellness 2023; 12: 1439–1449.
Ruan Y, Sun J, He J, et al. Effects of probiotcs on glycemic control: a systematic review and meta-analysis of randomized, controlled trials. PLOS ONE 2015; 10: e0132121.
Barthow C, Hood F, Crane J, et al. A randomised controlled trial of a probiotic and a prebiotic examining metabolic and mental health outcomes in adults with pre-diabetes. BMJ Open 2022; 12: e055214.
Wickens KL, Barthow CA, Murphy R, et al. Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial. Br J Nutr. 2017; 117: 804–813.
Li Y, Wu Y, Wu L, et al. The effects of probiotic administration on patients with prediabetes: a meta-analysis and systematic review. J Transl Med. 2022; 20: 498.
Muccioli GG, Naslain D, Bäckhed F, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010, 6: 392.
Tiderencel KA, Hutcheon DA, Ziegler J. Probiotics for the treatment of type 2 diabetes: a review of randomized controlled trials. Diabetes Metab Res Rev. 2020; 36: e3213.
Rittiphairoj T, Pongpirul K, Janchot K, et al. Probiotics contribute to glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Adv Nutr. 2021; 12: 722–734.
Tolhurst G, Heffron H, Lam YS, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012; 61: 364–371.
Winkler G, Kis JT, Schandl L. The “other” incretin − the therapeutic rediscovery of the glucose-dependent insulinotropic polypeptide. [A „másik” inkretin – a glükózdependens insulinotrop polipeptid terápiás újrafelfedezése.] Orv Hetil. 2023; 164: 210–218. [Hungarian]
Amyot J, Semache M, Ferdaoussi M, et al. Lipopolysaccharides impair insulin gene expression in isolated islets of Langerhans via toll-like receptor-4 and NF-κB signalling. PloS ONE 2012; 7: e36200.
Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition 2012; 28: 539–543.
Mohamadshahi M, Veissi M, Haidari F, et al. Effects of probiotic yogurt consumption on inflammatory biomarkers in patients with type 2 diabetes. Bioimpacts 2014; 4: 83–88.
Mishra SP, Wang S, Nagpal R, et al. Probiotics and prebiotics for the amelioration of type 1 diabetes: present and future perspectives. Microorganisms 2019; 7: 67.
Han H, Li Y, Fang J, et al. Gut microbiota and type 1 diabetes. Int J Mol Sci. 2018, 19: 995.
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.
Xie Z, Huang G, Wang Z, et al. Epigenetic regulation of Toll-like receptors and its roles in type 1 diabetes. J Mol Med. 2018; 96: 741–751.
Scott NA, Andrusaite A, Andersen P, et al. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis. Sci Transl Med. 2018; 10: eaao4755.
Ang Z, Ding JL. GPR41 andR43 in obesity and inflammation – protective or causative? Front Immunol. 2016; 7: 28.
Abdelazez A, Abdelmotaal H, Evivie SE, et al. Screening potential probiotic characteristics of Lactobacillus brevis strains in vitro and intervention effect on type I diabetes in vivo. Biomed Res Int. 2018; 2018: 7356173.
Le TK, Hosaka T, Nguyen TT, et al. Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice. Biomed Res. 2015; 36: 63–70.
Van Syoc EP, Damani J, DiMattia Z, et al. The effects of Bifidobacterium probiotic supplementation on blood glucose: a systematic review and meta-analysis of animal models and clinical evidence. Adv Nutr. 2024; 15: 100137.
Groele L, Szajewska H, Szalecki M, et al. Lack of effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised-controlled trial. BMJ Open Diabetes Res Care 2021; 9: e001523.
Marcial GE, Ford AL, Haller MJ, et al. Lactobacillus johnsonii N6.2 modulates the host immune responses: a double-blind, randomized trial in healthy adults. Front Immunol. 2017; 8: 655.
Verduci E, Mameli C, Amatruda M, et al. Early nutrition and risk of type 1 diabetes: the role of gut microbiota. Front Nutr. 2020; 7: 612377.
Obuchowska A, Gorczyca K, Standyło A, et al. Effects of probiotic supplementation during pregnancy on the future maternal risk of metabolic syndrome. Int J Mol Sci 2022; 23: 8253.
Mu J, Guo X, Zhou Y, et al. The effects of probiotics/synbiotics on glucose and lipid metabolism in women with gestational diabetes mellitus: a meta-analysis of randomized controlled trials. Nutrients 2023; 15: 1375.
Łagowska K, Malinowsky AM, Zawieja B, et al. Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis. Sci Rep. 2020; 10: 17796.
EFSA Panel on Diabetic Products, Nutrition and Allergics (NDA): Scientific opinion on the substantiation of health claims related to beta-glucans from oats and barley and maintenance of normal blood LDL-cholesterol concentrations (ID 1236, 1299), increase in satiety leading to a reduction in energy intake (ID 851, 852), reduction of post-prandial glycaemic responses (ID 821, 824), and “digestive function” (ID 850) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 2011; 9: 2207.
Ma T, Shen X, Shi X, et al. Targeting gut microbiota and metabolism as the major probiotic mechanism – an evidence-based review. Trends Food Sci Technol. 2023; 138: 178–198.
Wu T, Wang G, Xiong Z, et al. Probiotics interact with lipids metabolism and affect gut health. Front Nutr. 2022. 9: 917043.
Guo L, Wang L, Liu F, et al. Effect of bile salt hydrolase-active Lactobacillus plantarum KLDS 1.0344 on cholesterol metabolism in rats fed a high-cholesterol diet. J Funct Foods 2019; 61: 103497.
Falcinelli S, Rodiles A, Hatef A, et al. Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish. Sci Rep. 2017; 7: 5512.
Bagarolli RA, Tobar N, Oliveira AG, et al. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice. J Nutr Biochem. 2017; 50: 16–25.
Hirokane H, Nakahara M, Tachibana S, et al. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J Biol Chem. 2004; 279: 45685–45692.
Murakami M, Une N, Nishizawa M, et al. Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects. Springerplus 2013; 2: 20.
Winkler G, Wittmann I. Fat tissue as the primary target organ of insulin resistance in diabetes mellitus. From antidiabetics to „adipeuticums”. [A zsírszövet mint a 2-es típusú diabetest kísérő inzulinrezisztencia egyik célszerve. Az antidiabetikumoktól a fejlesztés alatt álló „adipeutikumokig”.] Orv Hetil. 2023; 164: 3–10. [Hungarian]
Bedros JR, Jermendy Gy, Gaál Zs, et al. Professional guidelines of the Ministry of the Interior on the diagnosis of diabetes mellitus, the antihyperglycaemic treatment and care of diabetics in adulthood (ed. Gy. Jermendy). [A Belügyminisztérium egészségügyi szakmai irányelve a diabetes mellitus kórismézéséről, a cukorbetegek antihyperglykaemiás kezeléséről és gondozásáról felnőttkorban. Klinikai szakmai irányelv 002243 (szerk. Jermendy Gy.).] Diabetol Hung. 2023; 31: 323–444. [Hungarian]
Bonora E, Cigolini M, Bosello O, et al. Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects. Curr Med Res Opin 1984; 9: 47–51.
Foretz M, Guigas B, Viollet B. Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023; 19: 460–476.
Zhang X, Zhao Y, Xu J, et al. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015; 5: 14405.
Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2014; 63: 727–735.
Napolitano A, Miller S, Nicholls AW, et al. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS ONE 2014; 9: e100778. Erratum: PLoS ONE 2014; 9: e106594.
Liu W, Luo Z, Zhou J, et al. Gut microbiota and antidiabetic drugs: perspectives of personalized treatment in type 2 diabetes mellitus. Front Cell Infect Microbiol. 2022; 12: 853771.
Montandon SA, Jornayvaz FR. Effects of antidiabetic drugs on gut microbiota composition. Genes (Basel) 2017; 8: 250.
Zhang L, Song P, Zhang X, et al. Alpha-glucosidase inhibitors alter gut microbiota and ameliorate collagen-induced arthritis. Front Pharmacol. 2019; 10: 1684.
Yan X, Feng B, Li P, et al. Microflora disturbance during progression of glucose intolerance and effect of sitagliptin: an animal study. J Diabetes Res. 2016; 2016: 2093171.
Kato S, Sato T, Fujita H, et al. Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms. Scientific Rep. 2021; 11: 9167.
Wang L, Li P, Tang Z, et al. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci Rep. 2016; 6: 33251.
Kusunoki M, Hisano F, Matsuda SI, et al. Effects of SGLT2 inhibitors on the intestinal bacterial flora in Japanese patients with type 2 diabetes mellitus. Drug Res. 2023; 73: 412–416.
Wu J, Chen Y, Yang H, et al. Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associated with increasing effect on the gut microbiota in db/db mice. Front Endocrinol. 2023; 14: 1026040.
Ojo O, Wang X, Ojo OO, 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: 5139.