Metabolic cooperation and proteolytic activity of the gut microbiome in children with congenital heart disease
Abstract
Introduction. Children with congenital heart disease exhibit alterations in the gut microbiome accompanied by changes in its metabolic activity. Short-chain fatty acids (SCFAs) are considered the most informative functional biomarkers of these metabolic changes. Objective. To investigate age-related characteristics of short-chain fatty acid production and the functional state of the gut microbiome in young children with congenital heart disease. Materials and Methods. The profile of short-chain fatty acids was analyzed in fecal samples obtained from young children with congenital heart disease and age-matched healthy controls. Concentrations of acetate, propionate, butyrate, total branched-chain fatty acids, the IsoCn/Cn ratio, and the anaerobic index were determined by gas–liquid chromatography according to the method developed by M.D. Ardatskaya. Participants were stratified into three age groups: 0–6 months, 6–12 months, and 1–3 years. Results and Discussion. Children with congenital heart disease demonstrated impaired metabolic activity of the gut microbiome across all age groups. The most pronounced finding was a reduction in butyrate production, reaching a 3.7-fold decrease in children aged 6–12 months compared with healthy controls. These changes were accompanied by reduced propionate levels, a lower anaerobic index, and an increased IsoCn/Cn ratio, indicating a predominance of proteolytic metabolism. The observed metabolic alterations suggest decreased activity of butyrate-producing obligate anaerobes, impaired saccharolytic fermentation, and the development of functional metabolic insufficiency of the gut microbiota. Conclusion. Young children with congenital heart disease exhibit age-dependent disturbances in short-chain fatty acid production, characterized by butyrate and propionate deficiency, enhanced proteolytic metabolism, and reduced functional activity of the obligate anaerobic gut microbiota.
Keywords
About the Authors
List of references
Агзамова Ш.А., Бабаджанова Ф.Р. Особенности кишечной микробиоты у детей с врожденными пороками сердца // Science and Innovation. – 2024. – Т. 3, специальный выпуск 44. – С. 18–25. Agzamova SA, Babadjanova FR. Osobennosti kishechnoy mikrobioty u detey s vrozhdennymi porokami serdtsa [Features of the gut microbiota in children with congenital heart defects]. Science and Innovation. 2024; 3 (Special Issue 44): 18–25.
Агзамова Ш.А., Бабаджанова Ф.Р. Роль короткоцепочечных жирных кислот в оценке состояния микробиоценоза кишечника и его диагностика у детей с врожденными пороками сердца // Международный журнал научной педиатрии. – 2025. – Т. 4, № 5. – С. 1067–1071. Agzamova SA, Babadjanova FR. Rol' korotkotsepochnykh zhirnykh kislot v otsenke sostoyaniya mikrobiotsenoza kishechnika i ego diagnostika u detey s vrozhdennymi porokami serdtsa [The role of short-chain fatty acids in the assessment and diagnosis of intestinal microbiocenosis in children with congenital heart defects]. Mezhdunarodnyy zhurnal nauchnoy pediatrii [International Journal of Scientific Pediatrics]. 2025; 4 (5): 1067–1071.DOI: 10.56121/2181-2926-2025-4-5-1067-1071.
Ардатская М.Д., Иконников Н.С., Минушкин О.Н. Способ разделения смеси жирных кислот фракции C2–C6 методом газожидкостной хроматографии: патент РФ № 2220755 C1. Заявка № 2002119447/15; опубликован 10.01.2004. Ardatskaya MD, Ikonnikov NS, Minushkin ON. Sposob razdeleniya smesi zhirnykh kislot fraktsii C2–C6 metodom gazozhidkostnoy khromatografii [Method for separating a mixture of C2–C6 fatty acids by gas–liquid chromatography]. Russian Federation Patent No. 2220755 C1. Application No. 2002119447/15; published 2004 Jan 10.
Арзикулов А.Ш., Абдумухтарова М.З. Современные представления о короткоцепочечных жирных кислотах и их роли в становлении желудочно-кишечного тракта // Новый день в медицине. – 2021. – № 2 (34). – С. 506–511. Arzikulov ASh, Abdumukhtarova MZ. Sovremennye predstavleniya o korotkotsepochnykh zhirnykh kislotakh i ikh roli v stanovlenii zheludochno-kishechnogo trakta [Current concepts of short-chain fatty acids and their role in the development of the gastrointestinal tract]. Novyy den' v meditsine [New Day in Medicine]. 2021; 2 (34): 506–511.
Бабаджанова Ф.Р., Давлатжонова Н. Роль биоимпедансометрии в изучении особенностей состава тела у детей с врождёнными пороками сердца // South Aral Region Medical Journal. – 2025. – Т. 1, № 3. – С. 243–253. Babadjanova FR, Davlatjonova N. Rol' bioimpedansometrii v izuchenii osobennostey sostava tela u detey s vrozhdennymi porokami serdtsa [The role of bioimpedance analysis in studying body composition in children with congenital heart defects]. South Aral Region Medical Journal. 2025; 1 (3): 243–253.
Всемирная организация здравоохранения. Врожденные аномалии [Электронный ресурс]. – Женева: ВОЗ, 2023. – URL: https://www.who.int/ru/news-room/fact-sheets/detail/birth-defect. World Health Organization. Congenital anomalies [Internet]. Geneva: WHO; 2023. Available from: https://www.who.int/ru/news-room/fact-sheets/detail/birth-defect
Agzamova SA, Babadjanova FR. Gut microbiome and short-chain fatty acid alterations after cardiopulmonary bypass are associated with nutritional and functional impairment in young children with congenital heart defects. Clin Exp Gastroenterol. 2026. DOI: 10.2147/CEG.S600414.
Feng D, Christensen JT, Yetman AT, et al. The microbiome’s relationship with congenital heart disease: more than a gut feeling. J Congenit Cardiol. 2021; 5. DOI: 10.1186/s40949-021-00060-4.
Fundora MP, Calamaro CJ, Wu Y, et al. Microbiome and growth in infants with congenital heart disease. J Pediatr. 2024; 274: 114169. DOI: 10.1016/j.jpeds.2024.114169.
Guo J, Han X, Huang W, et al. Gut dysbiosis during early life: causes, health outcomes, and amelioration via dietary intervention. Crit Rev Food Sci Nutr. 2022; 62: 7199–7221. DOI: 10.1080/10408398.2021.1912706.
Huang Y, Lu W, Zeng M, et al. Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health. Microbiome. 2022; 10: 245. DOI: 10.1186/s40168-022-01437-2.
Koc F, Magner C, Murphy K, et al. Gut microbiome in children with congenital heart disease after cardiopulmonary bypass surgery (GuMiBear Study). Pediatr Cardiol. 2025; 46 (7): 1868–1878. DOI: 10.1007/s00246-024-03634-2.
Lu Y, Zhang Y, Zhao X, et al. Microbiota-derived short-chain fatty acids: implications for cardiovascular and metabolic disease. Front Cardiovasc Med. 2022; 9: 900381. DOI: 10.3389/fcvm.2022.900381.
Luca A-C, Mindru D-E, Rosu S-T, et al. The gut microbiome in congenital heart disease: dysbiosis, intestinal barrier injury, and translational opportunities across the childhood—a narrative review. Children (Basel). 2026; 13 (5): 668. DOI: 10.3390/children13050668.
Shi B, Li H, He X. Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation. Gut Microbes. 2024; 16 (1): 2323237. DOI: 10.1080/19490976.2024.2323237.
Yang W, Yu T, Huang X, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun. 2020; 11: 4457. DOI: 10.1038/s41467-020-18262-6.
Zhao P, Zhao S, Tian J, Liu X. Significance of gut microbiota and short-chain fatty acids in heart failure. Nutrients. 2022; 14 (18): 3758. DOI: 10.3390/nu14183758.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.