Роль короткоцепочечных жирных кислот в формировании метаболически ассоциированной жировой болезни печени у детей

1. Васюкова О.В. Ожирение у детей и подростков: критерии диагноза. Ожирение и метаболизм. 2019;16(1):70-3 [Vasyukova OV. Obesity in children and adolescents: diagnosis criteria. Obesity and Metabolism. 2019;16(1):70-3 (in Russian)]. DOI:10.14341/omet10170
2. Latest WHO data on child obesity shows that southern European countries have the highest rate of childhood obesity/доклад Dr Joao Breda 25 ЕСO. WHO/Europe | Nutrition – Latest data shows southern European countries have highest rate of childhood obesity. Available at: https://www.who.int/europe/news/item/24-05-2018-latest-data-shows-southern-european-countries-have-h.... Accessed: 2023.
3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-57. DOI:10.1002/hep.29367
4. Ribeiro A, Igual-Perez MJ, Santos Silva E, Sokal EM. Childhood Fructoholism and Fructoholic Liver Disease. Hepatol Commun. 2019;3(1):44-51. DOI:10.1002/hep4.1291
5. Xanthakos SA. Nonalcoholic Steatohepatitis in Children. Clin Liver Dis. 2022;26(3):439-60. DOI:10.1016/j.cld.2022.05.001
6. Soderborg TK, Clark SE, Mulligan CE, et al. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018;9(1):4462. DOI:10.1038/s41467-018-06929-0
7. Bugianesi E, Bizzarri C, Rosso C, et al. Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease. Am J Gastroenterol. 2017;112(8):1277-86. DOI:10.1038/ajg.2017.140
8. Moreno-Fernández S, Garcés-Rimón M, Vera G, et al. High Fat/High Glucose Diet Induces Metabolic Syndrome in an Experimental Rat Model. Nutrients. 2018;10(10). DOI:10.3390/nu10101502
9. Лазебник Л. Б., Голованова Е. В., Туркина С. В., и др. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021;185(1):4-52 [Lazebnik LB, Golovanova EV, Turkina SV, et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52 (in Russian)]. DOI:10.31146/1682-8658-ecg-185-1-4-52
10. Ардатская М.Д. Пробиотики, пребиотики и метабиотики в клинической практике: руководство для врачей. М.: ГЭОТАР-Медиа, 2024 [Ardatskaia MD. Probiotiki, prebiotiki, i metabiotiki v klinicheskoi praktike: rukovodstvo dlia vrachei. Moscow: GEOTAR-Media, 2024 (in Russian)].
11. Kirundi J, Moghadamrad S, Urbaniak C. Microbiome-liver crosstalk: A multihit therapeutic target for liver disease. World J Gastroenterol. 2023;29(11):1651-68. DOI:10.3748/wjg.v29.i11.1651
12. Ардатская М.Д., Бельмер С.В., Добрица В.П., и др. Дисбиоз (дисбактериоз) кишечника: современное состояние проблемы, комплексная диагностика и лечебная коррекция. Экспериментальная и клиническая гастроэнтерология. 2015;117(5):13-50 [Ardatskaya MD, Bel’mer SV, Dobritsa VP, et al. Сolon dysbacteriosis (dysbiosis): modern state of the problem, comprehensive diagnosis and treatment correction. Eksperimental’naya i Klinicheskaya Gastroenterologiya. 2015;117(5):13-50 (in Russian)].
13. Ардатская М.Д. Клиническое значение короткоцепочечных жирных кислот при патологии желудочно-кишечного тракта. Авторефер. дис... д-ра мед. наук. М. 2003 [Ardatskaia MD. Klinicheskoe znachenie korotkotsepochechnykh zhirnykh kislot pri patologii zheludochno-kishechnogo trakta. Avtorefer. dis. d-ra med. nauk. Moscow. 2003 (in Russian)].
14. Yan H, Ajuwon KM. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS One. 2017;12(6):e0179586. DOI:10.1371/journal.pone.0179586
15. Dupraz L, Magniez A, Rolhion N, et al. Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells. Cell Rep. 2021;36(1):109332. DOI:10.1016/j.celrep.2021.109332
16. Corrêa-Oliveira R, Fachi JL, Vieira A, et al. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology. 2016;5(4):e73. DOI:10.1038/cti.2016.17
17. Булатова Е.М., Богданова Н.М., Лобанова Е.А., Габрусская Т.В. Кишечная микробиота: современные представления. Педиатрия. Журнал им. Г.Н. Сперанского. 2009;87(3):104-9 [Bulatova EM, Bogdanova NM, Lobanova ЕA, Gabrusskaya TV. Intestinal microbiota: current views. Pediatriya. Zhurnal imeni G.N. Speranskogo. 2009;87(3):104-9 (in Russian)].
18. Saint-Georges-Chaumet Y, Edeas M. Microbiota-mitochondria inter-talk: consequence for microbiota-host interaction. Pathog Dis. 2016;74(1):ftv096. DOI:10.1093/femspd/ftv096
19. Bishehsari F, Engen PA, Preite NZ, et al. Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA Production, and Suppresses Colon Carcinogenesis. Genes (Basel). 2018;9(2). DOI:10.3390/genes9020102
20. Haghikia A, Zimmermann F, Schumann P, et al. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. Eur Heart J. 2022;43(6):518-33. DOI:10.1093/eurheartj/ehab644
21. Martins MJ, Ascensão A, Magalhães J, et al. Molecular Mechanisms of NAFLD in Metabolic Syndrome. Biomed Res Int. 2015;2015:621080. DOI:10.1155/2015/621080
22. Craven M, Egan CE, Dowd SE, et al. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn’s disease. PLoS One. 2012;7(7):e41594. DOI:10.1371/journal.pone.0041594
23. Fachi JL, Sécca C, Rodrigues PB, et al. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. J Exp Med. 2020;217(3). DOI:10.1084/jem.20190489
24. Ranjbar R, Vahdati SN, Tavakoli S, et al. Immunomodulatory roles of microbiota-derived short-chain fatty acids in bacterial infections. Biomed Pharmacother. 2021;141:111817. DOI:10.1016/j.biopha.2021.111817
25. Philips CA, Augustine P, Yerol PK, et al. Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease. J Clin Transl Hepatol.
2020;8(1):87-99. DOI:10.14218/JCTH.2019.00035
26. Ардатская М.Д., Гарушьян Г.В., Мойсак Р.П., Топчий Т.Б. Роль короткоцепочечных жирных кислот в оценке состояния микробиоценоза кишечника и  его коррекции у пациентов с НАЖБП различных стадий. Экспериментальная и клиническая гастроэнтерология. 2019;161(1):106-16 [Ardatskaya MD, Garushyan GV, Moysak RP, Topchiy TB. Role of short chain fatty acids in evaluation of gut microbiocenosis disorders and their correction in patients with NAFLD of different stages. Experimental and Clinical Gastroenterology. 2019;(1):106-16 (in Russian)]. DOI:10.31146/1682-8658-ecg-161-1-106-116
27. van der Hee B, Wells JM. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol. 2021;29(8):700-12. DOI:10.1016/j.tim.2021.02.001
28. Cuda S, O’Hara V, Censani M, et al. Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024. Obes Pillars. 2024;9:100096. DOI:10.1016/j.obpill.2023.100096
29. Manning P, Murphy P, Wang K, et al. Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study. J Magn Reson Imaging. 2017;46(4):1149-58. DOI:10.1002/jmri.25663
30. Śliżewska K, Włodarczyk M, Sobczak M, et al. Comparison of the Activity of Fecal Enzymes and Concentration of SCFA in Healthy and Overweight Children. Nutrients. 2023;15(4):987. DOI:10.3390/nu15040987
31. Galuppo B, Cline G, Van Name M, et al. Colonic Fermentation and Acetate Production in Youth with and without Obesity. J Nutr. 2021;151(11):3292-8. DOI:10.1093/jn/nxab277
32. Mueller NT, Differding MK, Zhang M, et al. Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial. Diabetes Care. 2021;44(7):1462-71. DOI:10.2337/dc20-2257
33. Zhou P, Li R, Liu K. The Neighborhood Food Environment and the Onset of Child-Hood Obesity: A Retrospective Time-Trend Study in a Mid-sized City in China. Front Public Health. 2021;9:688767. DOI:10.3389/fpubh.2021.688767
34. Goffredo M, Mass K, Parks EJ, et al. Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth. J Clin Endocrinol Metab. 2016;101(11):4367-76. DOI:10.1210/jc.2016-1797
35. Orsso CE, Peng Y, Deehan EC, et al. Composition and Functions of the Gut Microbiome in Pediatric Obesity: Relationships with Markers of Insulin Resistance. Microorganisms. 2021;9(7):1490. DOI:10.3390/microorganisms9071490
36. de la Cuesta-Zuluaga J, Mueller NT, Álvarez-Quintero R, et al. Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. Nutrients. 2018;11(1):51.DOI:10.3390/nu11010051
37. Wong RJ, Ahmed A. Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian populations. World J Hepatol. 2014;6(5):263-73. DOI:10.4254/wjh.v6.i5.263
38. Liu W, Luo X, Tang J, et al. A bridge for short-chain fatty acids to affect inflammatory bowel disease, type 1 diabetes, and non-alcoholic fatty liver disease positively: by changing gut barrier. Eur J Nutr. 2021;60(5):2317-30. DOI:10.1007/s00394-020-02431-w
39. Жирков И.И., Гордиенко А.В., Сердюков Д.Ю., Дорохов Г.Ю. Ключевые моменты этиопатогенеза неалкогольной жировой болезни печени. Вестник Российской военно-медицинской академии. 2019;21(2):219-22 [Zhirkov II, Gordienko AV, Serdyukov DYu, Dorokhov GYu. Key points of etiopathogenesis of non-alcoholic fatty liver disease. Bulletin of the Russian Military Medical Academy. 2019;21(2):219-22 (in Russian)].

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1. Vasyukova OV. Obesity in children and adolescents: diagnosis criteria. Obesity and Metabolism. 2019;16(1):70-3 (in Russian). DOI:10.14341/omet10170
2. Latest WHO data on child obesity shows that southern European countries have the highest rate of childhood obesity/доклад Dr Joao Breda 25 ЕСO. WHO/Europe | Nutrition – Latest data shows southern European countries have highest rate of childhood obesity. Available at: https://www.who.int/europe/news/item/24-05-2018-latest-data-shows-southern-european-countries-have-h.... Accessed: 2023.
3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-57. DOI:10.1002/hep.29367
4. Ribeiro A, Igual-Perez MJ, Santos Silva E, Sokal EM. Childhood Fructoholism and Fructoholic Liver Disease. Hepatol Commun. 2019;3(1):44-51. DOI:10.1002/hep4.1291
5. Xanthakos SA. Nonalcoholic Steatohepatitis in Children. Clin Liver Dis. 2022;26(3):439-60. DOI:10.1016/j.cld.2022.05.001
6. Soderborg TK, Clark SE, Mulligan CE, et al. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018;9(1):4462. DOI:10.1038/s41467-018-06929-0
7. Bugianesi E, Bizzarri C, Rosso C, et al. Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease. Am J Gastroenterol. 2017;112(8):1277-86. DOI:10.1038/ajg.2017.140
8. Moreno-Fernández S, Garcés-Rimón M, Vera G, et al. High Fat/High Glucose Diet Induces Metabolic Syndrome in an Experimental Rat Model. Nutrients. 2018;10(10). DOI:10.3390/nu10101502
9. Lazebnik LB, Golovanova EV, Turkina SV, et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52 (in Russian). DOI:10.31146/1682-8658-ecg-185-1-4-52
10. Ardatskaia MD. Probiotiki, prebiotiki, i metabiotiki v klinicheskoi praktike: rukovodstvo dlia vrachei. Moscow: GEOTAR-Media, 2024 (in Russian).
11. Kirundi J, Moghadamrad S, Urbaniak C. Microbiome-liver crosstalk: A multihit therapeutic target for liver disease. World J Gastroenterol. 2023;29(11):1651-68. DOI:10.3748/wjg.v29.i11.1651
12. Ardatskaya MD, Bel’mer SV, Dobritsa VP, et al. Сolon dysbacteriosis (dysbiosis): modern state of the problem, comprehensive diagnosis and treatment correction. Eksperimental’naya i Klinicheskaya Gastroenterologiya. 2015;117(5):13-50 (in Russian).
13. Ardatskaia MD. Klinicheskoe znachenie korotkotsepochechnykh zhirnykh kislot pri patologii zheludochno-kishechnogo trakta. Avtorefer. dis. d-ra med. nauk. Moscow. 2003 (in Russian).
14. Yan H, Ajuwon KM. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS One. 2017;12(6):e0179586. DOI:10.1371/journal.pone.0179586
15. Dupraz L, Magniez A, Rolhion N, et al. Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells. Cell Rep. 2021;36(1):109332. DOI:10.1016/j.celrep.2021.109332
16. Corrêa-Oliveira R, Fachi JL, Vieira A, et al. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology. 2016;5(4):e73. DOI:10.1038/cti.2016.17
17. Bulatova EM, Bogdanova NM, Lobanova ЕA, Gabrusskaya TV. Intestinal microbiota: current views. Pediatriya. Zhurnal imeni G.N. Speranskogo. 2009;87(3):104-9 (in Russian).
18. Saint-Georges-Chaumet Y, Edeas M. Microbiota-mitochondria inter-talk: consequence for microbiota-host interaction. Pathog Dis. 2016;74(1):ftv096. DOI:10.1093/femspd/ftv096
19. Bishehsari F, Engen PA, Preite NZ, et al. Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA Production, and Suppresses Colon Carcinogenesis. Genes (Basel). 2018;9(2). DOI:10.3390/genes9020102
20. Haghikia A, Zimmermann F, Schumann P, et al. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. Eur Heart J. 2022;43(6):518-33. DOI:10.1093/eurheartj/ehab644
21. Martins MJ, Ascensão A, Magalhães J, et al. Molecular Mechanisms of NAFLD in Metabolic Syndrome. Biomed Res Int. 2015;2015:621080. DOI:10.1155/2015/621080
22. Craven M, Egan CE, Dowd SE, et al. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn’s disease. PLoS One. 2012;7(7):e41594. DOI:10.1371/journal.pone.0041594
23. Fachi JL, Sécca C, Rodrigues PB, et al. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. J Exp Med. 2020;217(3). DOI:10.1084/jem.20190489
24. Ranjbar R, Vahdati SN, Tavakoli S, et al. Immunomodulatory roles of microbiota-derived short-chain fatty acids in bacterial infections. Biomed Pharmacother. 2021;141:111817. DOI:10.1016/j.biopha.2021.111817
25. Philips CA, Augustine P, Yerol PK, et al. Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease. J Clin Transl Hepatol.
2020;8(1):87-99. DOI:10.14218/JCTH.2019.00035
26. Ardatskaya MD, Garushyan GV, Moysak RP, Topchiy TB. Role of short chain fatty acids in evaluation of gut microbiocenosis disorders and their correction in patients with NAFLD of different stages. Experimental and Clinical Gastroenterology. 2019;(1):106-16 (in Russian). DOI:10.31146/1682-8658-ecg-161-1-106-116
27. van der Hee B, Wells JM. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol. 2021;29(8):700-12. DOI:10.1016/j.tim.2021.02.001
28. Cuda S, O’Hara V, Censani M, et al. Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024. Obes Pillars. 2024;9:100096. DOI:10.1016/j.obpill.2023.100096
29. Manning P, Murphy P, Wang K, et al. Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study. J Magn Reson Imaging. 2017;46(4):1149-58. DOI:10.1002/jmri.25663
30. Śliżewska K, Włodarczyk M, Sobczak M, et al. Comparison of the Activity of Fecal Enzymes and Concentration of SCFA in Healthy and Overweight Children. Nutrients. 2023;15(4):987. DOI:10.3390/nu15040987
31. Galuppo B, Cline G, Van Name M, et al. Colonic Fermentation and Acetate Production in Youth with and without Obesity. J Nutr. 2021;151(11):3292-8. DOI:10.1093/jn/nxab277
32. Mueller NT, Differding MK, Zhang M, et al. Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial. Diabetes Care. 2021;44(7):1462-71. DOI:10.2337/dc20-2257
33. Zhou P, Li R, Liu K. The Neighborhood Food Environment and the Onset of Child-Hood Obesity: A Retrospective Time-Trend Study in a Mid-sized City in China. Front Public Health. 2021;9:688767. DOI:10.3389/fpubh.2021.688767
34. Goffredo M, Mass K, Parks EJ, et al. Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth. J Clin Endocrinol Metab. 2016;101(11):4367-76. DOI:10.1210/jc.2016-1797
35. Orsso CE, Peng Y, Deehan EC, et al. Composition and Functions of the Gut Microbiome in Pediatric Obesity: Relationships with Markers of Insulin Resistance. Microorganisms. 2021;9(7):1490. DOI:10.3390/microorganisms9071490
36. de la Cuesta-Zuluaga J, Mueller NT, Álvarez-Quintero R, et al. Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. Nutrients. 2018;11(1):51.DOI:10.3390/nu11010051
37. Wong RJ, Ahmed A. Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian populations. World J Hepatol. 2014;6(5):263-73. DOI:10.4254/wjh.v6.i5.263
38. Liu W, Luo X, Tang J, et al. A bridge for short-chain fatty acids to affect inflammatory bowel disease, type 1 diabetes, and non-alcoholic fatty liver disease positively: by changing gut barrier. Eur J Nutr. 2021;60(5):2317-30. DOI:10.1007/s00394-020-02431-w
39. Zhirkov II, Gordienko AV, Serdyukov DYu, Dorokhov GYu. Key points of etiopathogenesis of non-alcoholic fatty liver disease. Bulletin of the Russian Military Medical Academy. 2019;21(2):219-22 (in Russian).

О.В. Первишко*¹, М.Д. Ардатская², И.Н. Захарова³, Н.Г. Соболева⁴, У.А. Стинская¹, И.В. Бережная³, С.Н. Борзакова³, Д.К. Дмитриева<sup>3

1</sup>ФГБОУ ВО «Кубанский государственный медицинский университет» Минздрава России, Краснодар, Россия;
²ФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента РФ, Москва, Россия;
³ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
⁴Клиника «G8 Center», Краснодар, Россия
*ole-pervishko@yandex.ru

________________________________________________

Olesya V. Pervishko*¹, Maria D. Ardatskaya², Irina N. Zakharova³, Natalia G. Soboleva⁴, Ulyana A. Stinskaya¹, Irina V. Berezhnaya³, Svetlana N. Borzakova³, Diana K. Dmitrieva<sup>3

1</sup>Kuban State Medical University, Krasnodar, Russia;
²Central State Medical Academy of the President of the Russian Federation, Moscow, Russia;
³Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
⁴Clinic “G8 Center”, Krasnodar, Russia
*ole-pervishko@yandex.ru