Udział mikroflory jelitowej w rozwoju cukrzycy
Streszczenie
Ludzka mikroflora jelitowa składa się z licznych mikroorganizmów, które wchodząc w interakcję między sobą przyczyniają się do zachowania homeostazy w organizmie człowieka. W ciągu ostatnich lat można zaobserwować wzrost badań na temat mikroflory jelitowej, w tym potencjalnych powiązań z rozwojem zaburzeń metabolizmu węglowodanów. Według aktualnych danych mikrobiom jelitowy odgrywa istotną rolę w chorobach autoimmunologicznych, takich jak cukrzyca typu 1 oraz metabolicznych, w tym cukrzycy typu 2. Analiza badań przeprowadzonych na zwierzętach oraz ludziach wykazała, że pacjenci chorujący na cukrzycę charakteryzują się zmniejszoną różnorodnością flory jelitowej, zaburzonym stosunkiem niektórych gatunków bakterii oraz mniejszą ilością bakterii produkujących maślan. Do potencjalnych mechanizmów tłumaczących wpływ mikroflory jelitowej na rozwój cukrzycy, zalicza się interakcję z wrodzonym układem odpornościowym, zwiększoną przepuszczalność jelit, infiltrację endotoksyn, a także udział krótkołańcuchowych kwasów tłuszczowych i kwasu żółciowego. Co więcej, najnowsze doniesienia sugerują, że elementy probiotykoterapii lub przeszczep mikroflory kałowej od zdrowego dawcy, mogą stanowić obiecującą formę terapii dla pacjentów chorujących na cukrzycę. Należy jednak prowadzić dalsze badania w celu zmniejszenia częstości występowania zaburzeń gospodarki węglowodanowej oraz poprawy jakości życia pacjentów.
Słowa kluczowe: mikroflora jelitowacukrzyca typu 1cukrzyca typu 2przeszczep mikroflory kałowej
Referencje
- NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016; 387(10027): 1513–1530.
- Norris JM, Johnson RK, Stene LC. Type 1 diabetes-early life origins and changing epidemiology. Lancet Diabetes Endocrinol. 2020; 8(3): 226–238.
- Beam A, Clinger E, Hao L. Effect of Diet and Dietary Components on the Composition of the Gut Microbiota. Nutrients. 2021; 13(8).
- Hills RD, Pontefract BA, Mishcon HR, et al. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019; 11(7).
- Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018; 1693(Pt B): 128–133.
- Vos Wde, Tilg H, Hul MV, et al. Gut microbiome and health: mechanistic insights. Gut. 2022; 71(5): 1020–1032.
- Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018; 555(7695): 210–215.
- Christovich A, Luo XM. Gut Microbiota, Leaky Gut, and Autoimmune Diseases. Front Immunol. 2022; 13: 946248.
- Visser J, Rozing J, Sapone A, et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009; 1165: 195–205.
- Han H, Li Y, Fang J, et al. Gut Microbiota and Type 1 Diabetes. Int J Mol Sci. 2018; 19(4).
- 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.
- Huang Y, Li SC, Hu Ji, et al. Gut microbiota profiling in Han Chinese with type 1 diabetes. Diabetes Res Clin Pract. 2018; 141: 256–263.
- Demirci M, Bahar Tokman H, Taner Z, et al. Bacteroidetes and Firmicutes levels in gut microbiota and effects of hosts TLR2/TLR4 gene expression levels in adult type 1 diabetes patients in Istanbul, Turkey. J Diabetes Complications. 2020; 34(2): 107449.
- Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011; 5(1): 82–91.
- Knip M, Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol. 2016; 12(3): 154–167.
- Fu X, Liu Z, Zhu C, et al. Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr. 2019; 59(sup1): S130–S152.
- Davis-Richardson AG, Ardissone AN, Dias R, et al. Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes. Front Microbiol. 2014; 5: 678.
- Zhou He, Sun L, Zhang S, et al. Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms. Front Endocrinol (Lausanne). 2020; 11: 125.
- Wen Li, Ley RE, Volchkov PYu, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008; 455(7216): 1109–1113.
- Pussinen PJ, Havulinna AS, Lehto M, et al. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011; 34(2): 392–397.
- Mohammad S, Thiemermann C. Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions. Front Immunol. 2020; 11: 594150.
- Pappo I, Becovier H, Berry EM, et al. Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat. J Surg Res. 1991; 51(2): 106–112.
- Devaraj S, Dasu MR, Park SH, et al. Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes. Diabetologia. 2009; 52(8): 1665–1668.
- Velloso LA, Folli F, Saad MJ. TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation. Endocr Rev. 2015; 36(3): 245–271.
- Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007; 56(7): 1761–1772.
- Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007; 50(11): 2374–2383.
- Peng J, Narasimhan S, Marchesi JR, et al. Long term effect of gut microbiota transfer on diabetes development. J Autoimmun. 2014; 53: 85–94.
- Li Y, Liu Yu, Chu CQ. Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome. Mediators Inflamm. 2015; 2015: 638470.
- Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013; 64(2): 477–485.
- Jain R, Tartar DM, Gregg RK, et al. Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med. 2008; 205(1): 207–218.
- Kuriya G, Uchida T, Akazawa S, et al. Double deficiency in IL-17 and IFN-γ signalling significantly suppresses the development of diabetes in the NOD mouse. Diabetologia. 2013; 56(8): 1773–1780.
- Candon S, Perez-Arroyo A, Marquet C, et al. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes. PLoS One. 2015; 10(5): e0125448.
- Marwaha AK, Crome SQ, Panagiotopoulos C, et al. Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1 diabetes. J Immunol. 2010; 185(7): 3814–3818.
- Mu Q, Kirby J, Reilly CM, et al. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017; 8: 598.
- Damci T, Nuhoglu I, Devranoglu G, et al. Increased intestinal permeability as a cause of fluctuating postprandial blood glucose levels in Type 1 diabetic patients. Eur J Clin Invest. 2003; 33(5): 397–401.
- Meddings JB, Jarand J, Urbanski SJ, et al. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol. 1999; 276(4): G951–G957.
- El Asmar R, Panigrahi P, Bamford P, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002; 123(5): 1607–1615.
- Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020; 9.
- Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000; 355(9214): 1518–1519.
- Watts T, Berti I, Sapone A, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005; 102(8): 2916–2921.
- Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006; 55(5): 1443–1449.
- Yadav H, Jain S, Sinha PR. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition. 2007; 23(1): 62–68.
- Ahola A, Harjutsalo V, Forsblom C, et al. The Self-reported Use of Probiotics is Associated with Better Glycaemic Control and Lower Odds of Metabolic Syndrome and its Components in Type 1 Diabetes. Journal of Probiotics & Health. 2017; 05(04).
- Uusitalo U, Liu X, Yang J, et al. TEDDY Study Group. Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatr. 2016; 170(1): 20–28.
- Moravejolahkami AR, Shakibaei M, Fairley AM, et al. Probiotics, prebiotics, and synbiotics in type 1 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Diabetes Metab Res Rev. 2023 [Epub ahead of print]: e3655.
- Larsen N, Vogensen FK, van den Berg FWJ, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010; 5(2): e9085.
- Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012; 490(7418): 55–60.
- Wu X, Ma C, Han L, et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010; 61(1): 69–78.
- Lê KA, Li Y, Xu X, et al. Alterations in fecal Lactobacillus and Bifidobacterium species in type 2 diabetic patients in Southern China population. Front Physiol. 2012; 3: 496.
- Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005; 308(5728): 1635–1638.
- Chen PC, Chien YW, Yang SC. The alteration of gut microbiota in newly diagnosed type 2 diabetic patients. Nutrition. 2019; 63-64: 51–56.
- Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019; 76(3): 473–493.
- Ma Q, Li Y, Li P, et al. Research progress in the relationship between type 2 diabetes mellitus and intestinal flora. Biomed Pharmacother. 2019; 117: 109138.
- Karlsson FH, Tremaroli V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013; 498(7452): 99–103.
- Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001; 81(3): 1031–1064.
- Tan J, McKenzie C, Potamitis M, et al. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014; 121: 91–119.
- Wahlström A, Sayin SI, Marschall HU, et al. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016; 24(1): 41–50.
- Ridlon JM, Alves JM, Hylemon PB, et al. Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship. Gut Microbes. 2013; 4(5): 382–387.
- Zhao Y, Wu J, Li JV, et al. Gut microbiota composition modifies fecal metabolic profiles in mice. J Proteome Res. 2013; 12(6): 2987–2999.
- Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003; 361(9356): 512–519.
- Gomes JM, Costa Jd, Alfenas Rd. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism. 2017; 68: 133–144.
- Creely SJ, McTernan PG, Kusminski CM, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007; 292(3): E740–E747.
- Salamon D, Sroka-Oleksiak A, Kapusta P, et al. Characteristics of gut microbiota in adult patients with type 1 and type 2 diabetes based on next‑generation sequencing of the 16S rRNA gene fragment. Pol Arch Intern Med. 2018; 128(6): 336–343.
- Cani PD, Osto M, Geurts L, et al. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012; 3(4): 279–288.
- Yang K, Niu J, Zuo T, et al. Alterations in the Gut Virome in Obesity and Type 2 Diabetes Mellitus. Gastroenterology. 2021; 161(4): 1257–1269.e13.
- Barrea L, Vetrani C, Verde L, et al. Comprehensive Approach to Medical Nutrition Therapy in Patients with Type 2 Diabetes Mellitus: From Diet to Bioactive Compounds. Antioxidants (Basel). 2023; 12(4).
- Asemi Z, Zare Z, Shakeri H, et al. Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann Nutr Metab. 2013; 63(1-2): 1–9.
- Matsuzaki T, Nagata Y, Kado S, et al. Effect of oral administration of Lactobacillus casei on alloxan-induced diabetes in mice. APMIS. 1997; 105(8): 637–642.
- Tabuchi M, Ozaki M, Tamura A, et al. Antidiabetic effect of Lactobacillus GG in streptozotocin-induced diabetic rats. Biosci Biotechnol Biochem. 2003; 67(6): 1421–1424.
- 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(1): 63–70.
- Moya-Pérez A, Neef A, Sanz Y. Bifidobacterium pseudocatenulatum CECT 7765 Reduces Obesity-Associated Inflammation by Restoring the Lymphocyte-Macrophage Balance and Gut Microbiota Structure in High-Fat Diet-Fed Mice. PLoS One. 2015; 10(7): e0126976.
- Kikuchi K, Ben Othman M, Sakamoto K. Sterilized bifidobacteria suppressed fat accumulation and blood glucose level. Biochem Biophys Res Commun. 2018; 501(4): 1041–1047.
- Yoshida N, Emoto T, Yamashita T, et al. Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis. Circulation. 2018; 138(22): 2486–2498.
- Ziegler MC, Garbim Junior EE, Jahnke VS, et al. Impact of probiotic supplementation in a patient with type 2 diabetes on glycemic and lipid profile. Clin Nutr ESPEN. 2022; 49: 264–269.
- Kocsis T, Molnár B, Németh D, 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(1): 11787.
- Razmpoosh E, Javadi A, Ejtahed HS, et al. The effect of probiotic supplementation on glycemic control and lipid profile in patients with type 2 diabetes: A randomized placebo controlled trial. Diabetes Metab Syndr. 2019; 13(1): 175–182.
- Cani PD, de Vos WM. Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Front Microbiol. 2017; 8: 1765.
- Hansen CHF, Krych L, Nielsen DS, et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia. 2012; 55(8): 2285–2294.
- Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013; 110(22): 9066–9071.
- Dagdeviren S, Jung DY, Friedline RH, et al. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. FASEB J. 2017; 31(2): 701–710.
- Chambers ES, Viardot A, Psichas A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015; 64(11): 1744–1754.
- Psichas A, Sleeth ML, Murphy KG, 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 (Lond). 2015; 39(3): 424–429.
- Li J, Lin S, Vanhoutte PM, et al. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice. Circulation. 2016; 133(24): 2434–2446.
- Zhao S, Liu W, Wang J, et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J Mol Endocrinol. 2017; 58(1): 1–14.
- Belvoncikova P, Maronek M, Gardlik R. Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases. Int J Mol Sci. 2022; 23(18).
- Mocanu V, Zhang Z, Deehan EC, et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med. 2021; 27(7): 1272–1279.
- de Groot PF, Nikolic T, Imangaliyev S, et al. Oral butyrate does not affect innate immunity and islet autoimmunity in individuals with longstanding type 1 diabetes: a randomised controlled trial. Diabetologia. 2020; 63(3): 597–610.
- de Groot P, Nikolic T, Pellegrini S, et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut. 2021; 70(1): 92–105.
- Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012; 143(4): 913–6.e7.
- Kootte R, Levin E, Salojärvi J, et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metabolism. 2017; 26(4): 611–619.e6.
- de Groot P, Scheithauer T, Bakker GJ, et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut. 2020; 69(3): 502–512.
- Wu Z, Zhang B, Chen F, et al. Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study. Front Cell Infect Microbiol. 2022; 12: 1089991.