The purpose of the study was to analyze the sources of modern literature of domestic and foreign researchers on the role of intestinal microbiota in the pathogenesis of obesity. Results and discussion. The number of patients with obesity and associated cardio-metabolic disorders such as arterial hypertension, dyslipidemia, coronary heart disease, type 2 diabetes mellitus is constantly increasing. The increase in the prevalence of obesity and metabolic disorders cannot be attributed solely to changes in the human genome, dietary habits, or reduced levels of physical activity. In addition to the generally recognized reasons, one of the factors affecting the microorganism’s energy homeostasis is the intestinal microbiota. Intestinal microbiota is a collection of bacteria that inhabit the gastrointestinal tract. Intestinal microbiota and its active metabolites are involved in intestinal and hepatic gluconeogenesis, in fat homeostasis, in the synthesis of incretin hormones, and influence on the appetite regulation. Short-chain fatty acids are the most important metabolites of intestinal microbiota. Some bacteria of the Firmicutes, Eubacterium rectale/Roseburia phylum and Faecalibacterium prausnitzii and others produce short-chain fatty acids. Short-chain fatty acids perform a detoxifying function, maintain water and electrolyte balance, and participate in immune response processes by reducing the synthesis of pro-inflammatory interleukins. Intestinal microbiota is also considered as one of the potential sources of metabolic endotoxemia formation. The role of endotoxin in the human body is performed by one of the components of the outer membrane of gram-negative bacteria – lipopolysaccharide. It is constantly present in the blood, and at “physiological” concentrations it maintains the balance of the immune system, and “excessive” concentration of lipopolysaccharide in the blood leads to low-grade inflammation, endothelial dysfunction, and other inflammation-associated conditions. The degree of endotoxemia positively correlates with the severity of negative changes in lipid and carbohydrate metabolism. Also, intestinal microbiota can send signals to the central nervous system through the enteric nervous system or through the afferent fibers of the nervus vagus, both directly and through the release of neurotransmitters into the bloodstream. In turn, when transmitting signals from top to bottom, the autonomic nervous system and the hypothalamus-pituitary-adrenal axis affects intestinal microbiota, probably due to changes in the chemical composition of secretions. Conclusion. Members of intestinal microbiota can inhibit the activity of the enzyme adenosine monophosphate-activated protein kinase in muscle and liver, which entails a decrease in fatty acid oxidation and an increase in body fat. As it turned out, almost all known cardiovascular risk factors are to a greater or lesser extent interconnected with the state of the intestinal microbiota, so understanding its role and methods for correcting the composition of the intestinal microbiota can be of great importance in solving important issues in medicine

Keywords: intestinal microbiota, short-chain fatty acids, endotoxemia, appetite regulation, gluconeogenesis and lipogenesis

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1. Khan MJ, Gerasimidis K, Edwards CA, Shaikh MG. Role of Gut Microbiota in the Etiology of Obesity: Proposed Mechanisms and Review of the Literature. J Obes. 2016;2016:7353642. PMID: 27703805. PMCID: PMC5040794. https://doi.org/10.1155/2016/7353642
2. WHO. Obesity and overweight. 2017 Feb 14. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/
3. Smith KB, Smith MS. Obesity statistics. Prim Care. 2016;43:121-135. PMID: 26896205. https://doi.org/10.1016/j.pop.2015.10.001
4. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005 Jun 10;308(5728):1635-8. PMID: 15831718. PMCID: PMC1395357. https://doi.org/10.1126/science.1110591
5. Koval SM, Yushko KO, Snihurska IO. Kyshkova mikrobiota ta arterialna hipertenziia (ohliad literatury). Zaporizkyi Med Zh. 2020;22(4):561-567. https://doi.org/10.14739/2310-1210.2020.4.208409
6. Fadieienko HD, Bohun LV. Dysbyoz kyshechnyka v praktyke vracha-ynternysta [Intestinal dysbiosis in the practice of an internist]. Suchasna Gastroenterolohiia. 2013;1:89-96. [Russian]
7. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-36. PMID: 28512250. PMCID: PMC5433529. https://doi.org/10.1042/BCJ20160510
8. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018;57(1):1-24. PMID: 28393285. PMCID: PMC5847071. https://doi.org/10.1007/s00394-017-1445-8
9. Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol. 2016;5(4):e73. PMID: 27195116. PMCID: PMC4855267. https://doi.org/10.1038/cti.2016.17
10. Reichardt N, Duncan SH, Young P, Belenguer A, McWilliam Leitch C, Scott KP, et al. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014;8(6):1323-35. PMID: 24553467. PMCID: PMC4030238. https://doi.org/10.1038/ismej.2014.14
11. Pingitore A, Chambers ES, Hill T, Maldonado IR, Liu B, Bewick G. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimu-lates insulin secretion from human islets in vitro. Diabetes Obes Metab. 2017;19(2):257-65. PMID: 27761989. https://doi.org/10.1111/dom.12811
12. Shen X, Carlström M, Borniquel S, Jädert C, Kevil CG, Lundberg JO. Microbial Regulation of Host Hydrogen Sulfide Bioavailability and Metabolism. Free Radic Biol Med. 2013 Jul;60:195-200. PMID: 23466556. PMCID: PMC4077044. https://doi.org/10.1016/j.freeradbiomed.2013.02.024
13. Pichette J, Fynn-Sackey N, Gagnon J. Hydrogen Sulfide and Sulfate Prebiotic Stimulates the Secretion of GLP-1 and Improves Glycemia in Male Mice. Endocrinology. 2017;158(10):3416-25. PMID: 28977605. https://doi.org/10.1210/en.2017-00391
14. Salloum FN. Hydrogen sulfide and cardioprotection - Mechanistic insights and clinical translatability. Pharmacol Ther. 2015;152:11-7. PMID: 25913517. https://doi.org/10.1016/j.pharmthera.2015.04.004
15. Pichette J, Gagnon J. Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones. Oxid Med Cell Longev. 2016;2016:3285074. PMID: 27478532. PMCID: PMC4958482. https://doi.org/10.1155/2016/3285074
16. Gao J, Kang X, Liu H, Liu G, Bai M, Peng C, et al. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front Cell Infect Microbiol. 2018;8:13. PMID: 29468141. PMCID: PMC5808205. https://doi.org/10.3389/fcimb.2018.00013
17. Camilleri M. Serotonin in the Gastrointestinal Tract. Curr Opin Endocrinol Diabetes Obes. 2009;16(1):53-9. PMID: 19115522. PMCID: PMC2694720. https://doi.org/10.1097/MED.0b013e32831e9c8e
18. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes Metab Res. 2007;56:1761-1772. PMID: 17456850. https://doi.org/10.2337/db06-1491
19. Louis S, Tappu RM, Damms-Machado A, Damms-Machado A, Huson DH, Bischoff SC. Characterization of the gut microbial Community of Obese Patients Following a weight-loss intervention using whole Metagenome shotgun sequencing. PLoS One. 2016;11(2):e0149564. PMID: 26919743. PMCID: PMC4769288. https://doi.org/10.1371/journal.pone.0149564
20. Chevalier C, Stojanović O, Colin DJ, Suarez-Zamorano N, Tarallo V, Veyrat-Durebex C, et al. Gut Microbiota orchestrates energy homeostasis during cold. Cell. 2015;163(6):1360-1374. PMID: 26638070. https://doi.org/10.1016/j.cell.2015.11.004
21. Khan MY, Gupta P, Bihari B, Misra A, Pathak A, Vermaet VK. A review on obesity and its management. Int J Scientific Engineering Res. 2012;3(11).
22. Maenhaut N, Van de Voorde J. Regulation of vascular tone by adipocytes. BMC Medicine. 2011;9: 25. PMID: 21410966. PMCID: PMC3069942. https://doi.org/10.1186/1741-7015-9-259
23. Dahiya DK, Puniya M, Shandilya UK, Dhewa T, Kumar N, Kumar S. Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol. 2017;8:563. PMID: 28421057. PMCID: PMC5378938. https://doi.org/10.3389/fmicb.2017.00563
24. De Silva A, Bloom SR. Gut hormones and appetite control: a focus on PYY and GLP-1 as therapeutic targets in obesity. Gut Liver. 2012;6:10-20. PMID: 22375166. PMCID: PMC3286726. https://doi.org/10.5009/gnl.2012.6.1.10
25. Steinert R, Beglinger C, Langhans W. Intestinal GLP-1 and satiation: from man to rodents and back. Int J Obes. 2016;40:198-205. PMID: 26315842. https://doi.org/10.1038/ijo.2015.172
26. Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611. PMID: 24781306. PMCID: PMC4015327. https://doi.org/10.1038/ncomms4611
27. Royalty JE, Konradsen G, Eskerod O, Wulff BS, Hansen BS. Investigation of safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a long-acting α-MSH analogue in healthy overweight and obese subjects. J Clin Pharmacol. 2014;54(4):394-404. PMID: 24166760. PMCID: PMC4263154. https://doi.org/10.1002/jcph.211
28. Bäckberg M, Madjid N, Ogren SO, Meister B. Downregulated expression of agouti-related protein (AGRP) mRNA in the hypothalamic arcuate nucleus of hyperphagic and obese tub/tub mice. Brain Res Mol Brain Res. 2004;125(1-2):129-39. PMID: 15193430. https://doi.org/10.1016/j.molbrainres.2004.03.012
29. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 2016;20:8(1):42. PMID: 27098727. PMCID: PMC4839080. https://doi.org/10.1186/s13073-016-0303-2
30. Koval SM, Snihurska IO, Yushko KO, Mysnychenko OV, Halchynska VYu. Osoblyvosti skladu mikrobioty kyshechnyka u khvorykh na arterialnu hipertenziiu z abdominalnym ozhyrinniam [Features of the composition of the intestinal microbiota in patients with arterial hypertension with abdominal obesity]. Pathologia. 2021;18(3):303-310. [Ukrainian]. https://doi.org/10.14739/2310-1237.2021.3.236979
31. Aron-Wisnewsky J, Gaborit B, Dutour A, Clement K. Gut microbiota and non-alcoholic fatty liver disease: new insights. Clin Microbiol Infect. 2013;19(4):338-348. PMID: 23452163. https://doi.org/10.1111/1469-0691.12140
32. Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, et al. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes. 2012;36(6):817-825. PMID: 21829158. PMCID: PMC3374072. https://doi.org/10.1038/ijo.2011.153
33. Million M, Lagier JC, Yahav D, Paul M. Gut bacterial microbiota and obesity. Clin Microbiol Infect. 2013;19(4):305-313. PMID: 23452229. https://doi.org/10.1111/1469-0691.12172
34. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos N, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195. PMID: 19498350. https://doi.org/10.1038/oby.2009.167
35. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484. PMID: 19043404. PMCID: PMC2677729. https://doi.org/10.1038/nature07540
36. Miloslavsky D, Mysnychenko O, Penkova M, Schenyavska E, Koval S. Abdominal obesity and gut microbiota: review. Georgian Medical News. 2021;316-317:142-146.
37. Million M, Angelakis E, Maraninchi M, Henry M, Giorgi R, Valero R, et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacte rium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes (Lond). 2013;37(11):1460-1466. PMID: 23459324. PMCID: PMC3826031. https://doi.org/10.1038/ijo.2013.20
38. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos N, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195. PMID: 19498350. https://doi.org/10.1038/oby.2009.167
39. Zuo HJ, Xie ZM, Zhang WW, Li YR, Wang W, Ding XB, et al. Gut bacteria alteration in obese people and its relationship with gene polymorphism. World J Gastroenterol. 2011;17(8):1076-1081. PMID: 21448362. PMCID: PMC3057153. https://doi.org/10.3748/wjg.v17.i8.1076
40. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, et al. Human genetics shape the gut microbiome. Cell. 2014;159(4):789-799. PMID: 25417156. PMCID: PMC4255478. https://doi.org/10.1016/j.cell.2014.09.053
41. Rial SA, Karelis AD, Bergeron KF, Mounier C. Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals. Nutrients. 2016;8(5):281. PMID: 27187452. PMCID: PMC4882694. https://doi.org/10.3390/nu8050281
42. Serino M, Luche E, Gres S, Baylac A, Bergé M, Cenac C, et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2012;61(4):543-553. PMID: 22110050. PMCID: PMC3292714. https://doi.org/10.1136/gutjnl-2011-301012