Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd2762310.32607/actanaturae.27623ReviewsОбзорыReview ArticleGut microbiota and short-chain fatty acids in the pathogenesis of necrotizing enterocolitis in very preterm infantsКишечная микробиота и короткоцепочечные жирные кислоты в патогенезе некротизирующего энтероколита у глубоко недоношенных новорожденныхhttps://orcid.org/0000-0002-8397-35746507367648C-9408-20143377-5462KukaevEvgenii N.КукаевЕвгений Николаевич
Russian Federation

V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences

Институт энергетических проблем химической физики им. В.Л. Тальрозе ФГБУН Федерального исследовательского центра химической физики имени Н.Н. Семёнова РАН

e_kukaev@oparina4.ru8552-7215TokarevaAlisa O.ТокареваАлиса Олеговна
Russian Federation
a_tokareva@oparina4.ruhttps://orcid.org/0000-0002-5178-5659572142204539546-0975Krogh-JensenOlga A.Крог-ЙенсенОльга Александровна
Russian Federation
o_krogh@oparina4.ruhttps://orcid.org/0000-0001-8929-299157202802436AAJ-6896-20215464-0656LenyushkinaAnna A.ЛёнюшкинаАнна Алексеевна
Russian Federation
a-lenushkina@yandex.ruhttps://orcid.org/0000-0001-6650-591550462424600Y-6378-20193673-7263StarodubtsevaNataliia L.СтародубцеваНаталия Леонидовна
Russian Federation
n_starodubtseva@oparina4.ruNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Министерства здравоохранения Российской ФедерацииN.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of SciencesФГБУН Федерального исследовательского центра химической физики имени Н.Н. Семёнова РАНFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет)Moscow Institute of Physics and TechnologyФедеральное государственное автономное образовательное учреждение высшего образования «Московский физико-технический институт (национальный исследовательский университет)»0412202517438512901202525062025Copyright ©; 2025, Kukaev E.N., Tokareva A.O., Krogh-Jensen O.A., Lenyushkina A.A., Starodubtseva N.L.Copyright ©; 2025, Кукаев Е.Н., Токарева А.О., Крог-Йенсен О.А., Лёнюшкина А.А., Стародубцева Н.Л.2025Kukaev E.N., Tokareva A.O., Krogh-Jensen O.A., Lenyushkina A.A., Starodubtseva N.L.Кукаев Е.Н., Токарева А.О., Крог-Йенсен О.А., Лёнюшкина А.А., Стародубцева Н.Л.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/27623

The development of a symbiotic gut ecosystem is a crucial step in postnatal adaptation. The gut microbiome of very preterm infants is characterized by an overall instability, reduced microbial diversity, and a predominance of Gram-negative Proteobacteria, all factors associated with an increased risk of necrotizing enterocolitis (NEC). Short-chain fatty acids (SCFAs) are the key bacterial metabolites that are essential for maintaining intestinal homeostasis, supporting immune development, enhancing intestinal barrier integrity, and reducing inflammation. This review examines the role of gut microbiota and SCFAs in neonatal NEC, with a focus on potential diagnostic and therapeutic strategies. Clinical studies have consistently demonstrated a significant decrease in total SCFA levels and individual bacterial metabolites in preterm infants with NEC. This finding has been corroborated by various experimental models. Clarification of the role of SCFAs in NEC pathogenesis, determination of their diagnostic utility, and assessment of the feasibility of developing comprehensive pro- and postbiotic formulations require multi-center, multi-omics investigations that include a large cohort of very preterm infants.

Формирование симбиотической кишечной экосистемы – необходимый этап адаптации новорожденного ребенка. Микробиом кишечника глубоко недоношенных новорожденных характеризуется нестабильностью, снижением микробного разнообразия с преобладанием грамотрицательных Proteobacteria, что сопряжено с одним из ключевых патогенетических механизмов развития некротизирующего энтероколита (НЭК). Короткоцепочечные жирные кислоты (КЦЖК) представляют собой основные бактериальные метаболиты, играющие важную роль в поддержании целостности кишечного барьера и регуляции иммунологической реактивности кишечника. В обзоре обсуждается роль кишечной микробиоты и КЦЖК при некротизирующем энтероколите у новорожденных в аспекте потенциальных диагностических и терапевтических возможностей. В клинических исследованиях содержания КЦЖК в кале недоношенных новорожденных с НЭК обнаружено выраженное снижение общего уровня КЦЖК и большинства бактериальных метаболитов в отдельности, что подтверждено в ряде модельных экспериментов. Для уточнения роли КЦЖК в развитии НЭК, определения их диагностического потенциала и возможностей создания комплексных про- и постбиотических формул необходимо проведение многоцентровых мультиомиксных исследований на большой выборке глубоко недоношенных новорожденных.

necrotizing enterocolitisvery premature infantsdiagnosticsgas chromatography-mass spectrometryshort-chain fatty acidsgut microbiotaнекротизирующий энтероколитглубоко недоношенные новорожденныедиагностикагазовая хроматография с масс-спектрометриейкороткоцепочечные жирные кислотымикробиотаРоссийский научный фондRussian Science Foundation24-25-00068Neu J, Mshvildadze M, Mai V. A roadmap for understanding and preventing necrotizing enterocolitis. Curr Gastroenterol Rep. 2008;10(5):450–457. doi: 10.1007/s11894-008-0084-xNeu J, Mshvildadze M, Mai V. A roadmap for understanding and preventing necrotizing enterocolitis. Current Gastroenterology Reports. 2008;10(5):450-457. doi: 10.1007/s11894-008-0084-xAhearn-Ford S, Berrington JE, Stewart CJ. Development of the gut microbiome in early life. Exp Physiol. 2022;107(5):415–421. doi: 10.1113/EP089919Ahearn-Ford S, Berrington JE, Stewart CJ. Development of the gut microbiome in early life. Experimental Physiology. 2022;107(5):415-421. doi: 10.1113/EP089919Thänert R, Sawhney SS, Schwartz DJ, Dantas G. The resistance within: Antibiotic disruption of the gut microbiome and resistome dynamics in infancy. Cell Host Microbe. 2022;30(5):675–683. doi: 10.1016/j.chom.2022.03.013Thänert R, Sawhney SS, Schwartz DJ, Dantas G. The resistance within: Antibiotic disruption of the gut microbiome and resistome dynamics in infancy. Cell Host and Microbe. 2022;30(5):675-683. doi: 10.1016/j.chom.2022.03.013Reichardt N, Duncan SH, Young P, et al. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014;8(6):1323–1335. doi: 10.1038/ismej.2014.14Reichardt N, Duncan SH, Young P, et al. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME Journal. 2014;8(6):1323-1335. doi: 10.1038/ismej.2014.14Scheiman J, Luber JM, Chavkin TA, et al. Meta-omic analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med. 2019;25(7):1104–1109. doi: 10.1038/s41591-019-0485-4Scheiman J, Luber JM, Chavkin TA, et al. Meta’omic analysis of elite athletes identifies a performance- enhancing microbe that functions via lactate metabolism. Nature Medicine. 2019;25(7):1104-1109. doi: 10.1038/s41591-019-0485-4.MetaNikitina IV, Lenyushkina AA, Krogh-Jensen OA, et al. Recurrent necrotizing enterocolitis: predictors, biological markers, diagnostic signs, and therapeutic approaches – a year-long case study. Neonatology. 2024;12(3):66–77. doi: 10.33029/2308-2402-2024-12-3-66-77Nikitina IV, Lenyushkina AA, Krogh-Jensen OA, et al. Recurrent necrotizing enterocolitis: predictors, biological markers, diagnostic signs, and therapeutic approaches – a year-long case study. Neonatology: News, Opinions, Training. 2024;12(3):66-77. doi: 10.33029/2308–2402-2024-12-3-66-77Jones IH, Hall NJ. Contemporary Outcomes for Infants with Necrotizing Enterocolitis – A Systematic Review. J Pediatr. 2020;220:86–92.e3. doi: 10.1016/j.jpeds.2019.11.011Jones IH, Hall NJ. Contemporary Outcomes for Infants with Necrotizing Enterocolitis—A Systematic Review. Journal of Pediatrics. 2020;220:86-92.e3. doi: 10.1016/j.jpeds.2019.11.011Scheese DJ, Sodhi CP, Hackam DJ. New insights into the pathogenesis of necrotizing enterocolitis and the dawn of potential therapeutics. Semin Pediatr Surg. 2023;32(3):151309. doi: 10.1016/j.sempedsurg.2023.151309Scheese DJ, Sodhi CP, Hackam DJ. New insights into the pathogenesis of necrotizing enterocolitis and the dawn of potential therapeutics. Seminars in Pediatric Surgery. 2023;32(3):151309. doi: 10.1016/j.sempedsurg.2023.151309Zhou Q, Niño DF, Yamaguchi Y, et al. Necrotizing enterocolitis induces T lymphocyte–mediated injury in the developing mammalian brain. Sci Transl Med. 2021;13(575): eaay6621. doi: 10.1126/scitranslmed.aay6621Zhou Q, Niño DF, Yamaguchi Y, et al. Necrotizing enterocolitis induces T lymphocyte–mediated injury in the developing mammalian brain. Science Translational Medicine. 2021;13(575):1-30. doi: 10.1126/SCITRANSLMED.AAY6621Fullerton BS, Hong CR, Velazco CS, et al. Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study. J Pediatr Surg. 2018;53(1):101–107. doi: 10.1016/j.jpedsurg.2017.10.029Fullerton BS, Hong CR, Velazco CS, et al. Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study. Journal of Pediatric Surgery. 2018;53(1):101-107. doi: 10.1016/j.jpedsurg.2017.10.029Pupysheva AF, Savelyeva EI, Piskunova VV, et al. Fecal Calprotectin Levels Dynamics in Newborns with High-Risk of Necrotizing Enterocolitis. Pediatr Pharmacol. 2023;20(1):51–55. doi: 10.15690/pf.v20i1.2529Pupysheva AF, Savelyeva EI, Piskunova VV, et al. Fecal Calprotectin Levels Dynamics in Newborns with High-Risk of Necrotizing Enterocolitis. Pediatric Pharmacology. 2023;20(1):51-55. doi: 10.15690/pf.v20i1.2529Thakkar HS, Lakhoo K. Necrotizing enterocolitis. Surgery (Oxf). 2022;40(11):713–716. doi: 10.1016/j.mpsur.2022.09.007Thakkar HS, Lakhoo K. Necrotizing enterocolitis. Surgery (United Kingdom). 2022;40(11):713-716. doi: 10.1016/j.mpsur.2022.09.007Hsu CY, Khachatryan LG, Younis NK, et al. Microbiota-derived short chain fatty acids in pediatric health and diseases: from gut development to neuroprotection. Front Microbiol. 2024;15:1456793. doi: 10.3389/fmicb.2024.1456793Hsu CY, Khachatryan LG, Younis NK, et al. Microbiota-derived short chain fatty acids in pediatric health and diseases: from gut development to neuroprotection. Frontiers in Microbiology. 2024;15(October):1456793. doi: 10.3389/fmicb.2024.1456793Facchin S, Bertin L, Bonazzi E, et al. Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications. Life (Basel). 2024;14(5):559. doi: 10.3390/life14050559Facchin S, Bertin L, Bonazzi E, et al. Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications. Life. 2024;14(5):1-44. doi: 10.3390/life14050559He Y, Du W, Xiao S, et al. Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells. J Transl Med. 2021;19(1):510. doi: 10.1186/s12967-021-03109-5He Y, Du W, Xiao S, et al. Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells. Journal of Translational Medicine. 2021;19(1):510. doi: 10.1186/s12967-021-03109-5Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17(5):690–703. doi: 10.1016/j.chom.2015.04.004Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host and Microbe. 2015;17(5):690-703. doi: 10.1016/j.chom.2015.04.004Cuna A, Morowitz MJ, Ahmed I, Umar S, Sampath V. Dynamics of the preterm gut microbiome in health and disease. Am J Physiol Gastrointest Liver Physiol. 2021;320(4):G411–G419. doi: 10.1152/ajpgi.00399.2020Cuna A, Morowitz MJ, Ahmed I, Umar S, Sampath V. Dynamics of the preterm gut microbiome in health and disease. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2021;320(4):G411-G419. doi: 10.1152/AJPGI.00399.2020Yao Y, Cai X, Ye Y, Wang F, Chen F, Zheng C. The Role of Microbiota in Infant Health: From Early Life to Adulthood. Front Immunol. 2021;12:708472. doi: 10.3389/fimmu.2021.708472Yao Y, Cai X, Ye Y, Wang F, Chen F, Zheng C. The Role of Microbiota in Infant Health: From Early Life to Adulthood. Frontiers in Immunology. 2021;12(October):708472. doi: 10.3389/fimmu.2021.708472Olm MR, Brown CT, Brooks B, et al. Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes & exhibit different in situ growth rates. Genome Res. 2017;27(4):601–612. doi: 10.1101/gr.213256.116Olm MR, Brown CT, Brooks B, et al. Identical bacterial populations colonize premature infant gut, skin, & oral microbiomes & exhibit different in situ growth rates. Genome Research. 2017;27(4):601-612. doi: 10.1101/gr.213256.116Gibson MK, Wang B, Ahmadi S, et al. Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome. Nat Microbiol. 2016;1:16024. doi: 10.1038/nmicrobiol.2016.24Gibson MK, Wang B, Ahmadi S, et al. Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome. Nature Microbiology. 2016;1:16024. doi: 10.1038/nmicrobiol.2016.24.DevelopmentalGasparrini AJ, Wang B, Sun X, et al. Metagenomic signatures of early life hospitalization and antibiotic treatment in the infant gut microbiota and resistome persist long after discharge. Nat Microbiol. 2016;4(12):2285–2297. doi: 10.1038/s41564-019-0550-2Gasparrini AJ, Wang B, Sun X, et al. Metagenomic signatures of early life hospitalization and antibiotic treatment in the infant gut microbiota and resistome persist long after discharge. Nature Microbiology. 2016;4(12):2285-2297. doi: 10.1038/s41564-019-0550-2.MetagenomicWandro S, Osborne S, Enriquez C, Bixby C, Arrieta A, Whiteson K. The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis. mSphere. 2018;3(3):e00104–18. doi: 10.1128/msphere.00104-18Wandro S, Osborne S, Enriquez C, Bixby C, Arrieta A, Whiteson K. The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis. mSphere. 2018;3(3):e00104-18. doi: 10.1128/msphere.00104-18Young GR, van der Gast CJ, Smith DL, Berrington JE, Embleton ND, Lanyon C. Acquisition and Development of the Extremely Preterm Infant Microbiota Across Multiple Anatomical Sites. J Pediatr Gastroenterol Nutr. 2020;70(1):12–19. doi: 10.1097/MPG.0000000000002549Young GR, Van Der Gast CJ, Smith DL, Berrington JE, Embleton ND, Lanyon C. Acquisition and Development of the Extremely Preterm Infant Microbiota Across Multiple Anatomical Sites. Journal of Pediatric Gastroenterology and Nutrition. 2020;70(1):12-19. doi: 10.1097/MPG.0000000000002549Patel AL, Mutlu EA, Sun Y, et al. Longitudinal Survey of Microbiota in Hospitalized Preterm Very Low Birth Weight Infants. J Pediatr Gastroenterol Nutr. 2016;62(2):292–303. doi: 10.1097/MPG.0000000000000913Patel AL, Mutlu EA, Sun Y, et al. Longitudinal Survey of Microbiota in Hospitalized Preterm Very Low Birth Weight Infants. J Pediatr Gastroenterol Nutr. 2016;62(2):292-303. doi: 10.1097/MPG.0000000000000913.LongitudinalStewart CJ, Embleton ND, Marrs ECL, et al. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease. Microbiome. 2016;4(1):67. doi: 10.1186/s40168-016-0216-8Unger S, Stintzi A, Shah P, Mack D, O’Connor DL. Gut microbiota of the very-low-birth-weight infant. Pediatr Res. 2015;77(1–2):205–213. doi: 10.1038/pr.2014.162Unger S, Stintzi A, Shah P, Mack D, O’Connor DL. Gut microbiota of the very-low-birth-weight infant. Pediatric Research. 2015;77(1):205-213. doi: 10.1038/pr.2014.162Wang Y, Hoenig JD, Malin KJ, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J. 2009;3(8):944–954. doi: 10.1038/ismej.2009.37Wang Y, Hoenig JD, Malin KJ, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. Isme. 2009;3(8):944-954. doi: 10.1038/ismej.2009.37.16SLemme-Dumit JM, Song Y, Lwin HW, et al. Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut. Front Immunol. 2022;13:815046. doi: 10.3389/fimmu.2022.815046Lemme-Dumit JM, Song Y, Lwin HW, et al. Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut. Frontiers in Immunology. 2022;13(February):815046. doi: 10.3389/fimmu.2022.815046Torrazza RM, Ukhanova M, Wang X, et al. Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis. PLoS One. 2013;8(12):e83304. doi: 10.1371/journal.pone.0083304Liu XC, Du TT, Gao X, et al. Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study. Front Microbiol. 2022;13:969656. doi: 10.3389/fmicb.2022.969656Liu XC, Du TT, Gao X, et al. Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study. Frontiers in Microbiology. 2022;13(August):969656. doi: 10.3389/fmicb.2022.969656Warner PBB, Deych E, Zhou Y, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2017;387(10031):1928–1936. doi: 10.1016/S0140-6736(16)00081-7Warner PBB, Deych E, Zhou Y, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2017;387(10031):1928-1936. doi: 10.1016/S0140-6736(16)00081-7.GutMorrow AL, Lagomarcino AJ, Schibler KR, et al. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants. Microbiome. 2013;1(1):13. doi: 10.1186/2049-2618-1-13Olm MR, Bhattacharya N, Crits-Christoph A, et al. Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria. Sci Adv. 2019;5(12):eaax5727. doi: 10.1126/sciadv.aax5727Olm MR, Bhattacharya N, Crits-Christoph A, et al. Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria. Science Advances. 2019;5(12):eaax5727. doi: 10.1126/sciadv.aax5727Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol. 2007;19(2):70–83. doi: 10.1016/j.smim.2007.04.002Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Seminars in Immunology. 2007;19(2):70-83. doi: 10.1016/j.smim.2007.04.002Mih B, Good M. Impact of Toll-like receptor 4 signaling in necrotizing enterocolitis: The state of the science. Clin Perinatol. 2019;46(1):145–157. doi: 10.1016/j.clp.2018.09.007Mih B, Good M. Impact of Toll-like receptor 4 signaling in necrotizing enterocolitis: The state of the science. Clinics in Perinatology. 2019;46(1):145-157. doi: 10.1177/0022146515594631.MarriageHealy DB, Ryan CA, Ross RP, Stanton C, Dempsey EM. Clinical implications of preterm infant gut microbiome development. Nat Microbiol. 2022;7(1):22–33. doi: 10.1038/s41564-021-01025-4Healy DB, Ryan CA, Ross RP, Stanton C, Dempsey EM. Clinical implications of preterm infant gut microbiome development. Nature Microbiology. 2022;7(January):22-33. doi: 10.1038/s41564-021-01025-4 ClinicalNikitina IV, Donnikov AE, Krogh-Jensen OA, et al. Genetic predictors of necrotizing enterocolitis in neonates. Akush Ginekol (Russian Fed). 2020;(12):150–158. doi: 10.18565/aig.2020.12.150-158Nikitina IV, Donnikov AE, Krogh-Jensen OA, et al. Genetic predictors of necrotizing enterocolitis in neonates. Obstetrics and Gynecology. 2020;(12):150-158. doi: 10.18565/aig.2020.12.150-158Krogh-Jensen OA, Nikitina IV, Bragina ON, et al. Body surface cultures in preterm neonates on the first day of life: clinical usefulness. Akush Ginekol (Russian Fed). 2022;(8):108–123. doi: 10.18565/aig.2022.8.108-123Krogh-Jensen OA, Nikitina IV, Bragina ON, et al. Body surface cultures in preterm neonates on the first day of life: clinical usefulness. Obstetrics and Gynecology 2023;(8):108-123. doi: 10.18565/aig.2022.8.108-123Gupta S, Mortensen MS, Schjørring S, et al. Amplicon sequencing provides more accurate microbiome information in healthy children compared to culturing. Commun Biol. 2019;2:291. doi: 10.1038/s42003-019-0540-1Gupta S, Mortensen MS, Schjørring S, et al. Amplicon sequencing provides more accurate microbiome information in healthy children compared to culturing. Communications Biology. 2019;2:291. doi: 10.1038/s42003-019-0540-1Deurenberg RH, Bathoorn E, Chlebowicz MA, et al. Application of next generation sequencing in clinical microbiology and infection prevention. J Biotechnol. 2017;243:16–24. doi: 10.1016/j.jbiotec.2016.12.022Deurenberg RH, Bathoorn E, Chlebowicz MA, et al. Application of next generation sequencing in clinical microbiology and infection prevention. Journal of Biotechnology. 2017;243:16-24. doi: 10.1016/j.jbiotec.2016.12.022Woo PCY, Lau SKP, Teng JLL, Tse H, Yuen KY. Then and now: Use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clin Microbiol Infect. 2008;14(10):908–934. doi: 10.1111/j.1469-0691.2008.02070.xWoo PCY, Lau SKP, Teng JLL, Tse H, Yuen KY. Then and now: Use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clinical Microbiology and Infection. 2008;14(10):908-934. doi: 10.1111/j.1469-0691.2008.02070.xSher Y, Olm MR, Raveh-Sadka T, et al. Combined analysis of microbial metagenomic and metatranscriptomic sequencing data to assess in situ physiological conditions in the premature infant gut. PLoS One. 2020;15(3):e0229537. doi: 10.1371/journal.pone.0229537Wishart DS, Oler E, Peters H, et al. MiMeDB: the Human Microbial Metabolome Database. Nucleic Acid Res. 2023;51(D1):D611–D620. doi: 10.1093/nar/gkac868Wishart DS, Oler E, Peters H, et al. MiMeDB: the Human Microbial Metabolome Database. Nucleic Acids Research. 2023;51(1 D):D611-D620. doi: 10.1093/nar/gkac868Liu M, Lu Y, Xue G, et al. Role of short-chain fatty acids in host physiology. Animal Model Exp Med. 2024;7(5):641–652. doi: 10.1002/ame2.12464Liu M, Lu Y, Xue G, et al. Role of short-chain fatty acids in host physiology. Animal Models and Experimental Medicine. 2024;(June):641-652. doi: 10.1002/ame2.12464Takeuchi T, Nakanishi Y, Ohno H. Microbial Metabolites and Gut Immunology. Annu Rev Immunol. 2024;42(1):153–178. doi: 10.1146/annurev-immunol-090222-102035Takeuchi T, Nakanishi Y, Ohno H. Microbial Metabolites and Gut Immunology. Annual review of immunology. 2024;42(1):153-178. doi: 10.1146/annurev-immunol-090222-102035Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: Mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37–49. doi: 10.1017/S0029665120006916Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: Mechanisms and functional importance in the gut. Proceedings of the Nutrition Society. 2021;80(1):37-49. doi: 10.1017/S0029665120006916den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–2340. doi: 10.1194/jlr.R036012den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research. 2013;54(9):2325-2340. doi: 10.1194/jlr.R036012Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189–200. doi: 10.1080/19490976.2015.1134082Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189-200. doi: 10.1080/19490976.2015.1134082Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The Role of Short-Chain Fatty Acids in Health and Disease. Adv Immunol. 2014:121:91–119. doi: 10.1016/B978-0-12-800100-4.00003-9Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The Role of Short-Chain Fatty Acids in Health and Disease. In: Advances in Immunology. Vol 121. 1st ed. Elsevier Inc.; 2014:91-119. doi: 10.1016/B978-0-12-800100-4.00003-9Barcenilla A, Pryde SE, Martin JC, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66(4):1654–1661. doi: 10.1128/AEM.66.4.1654-1661.2000Barcenilla A, Pryde SE, Martin JC, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Applied and Environmental Microbiology. 2000;66(4):1654-1661. doi: 10.1128/AEM.66.4.1654-1661.2000Louis P, Young P, Holtrop G, Flint HJ. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol. 2010;12(2):304–314. doi: 10.1111/j.1462-2920.2009.02066.xLouis P, Young P, Holtrop G, Flint HJ. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environmental Microbiology. 2010;12(2):304-314. doi: 10.1111/j.1462-2920.2009.02066.xTurroni F, Milani C, Duranti S, Mahony J, van Sinderen D, Ventura M. Glycan Utilization and Cross-Feeding Activities by Bifidobacteria. Trends Microbiol. 2018;26(4):339–350. doi: 10.1016/j.tim.2017.10.001Turroni F, Milani C, Duranti S, Mahony J, van Sinderen D, Ventura M. Glycan Utilization and Cross-Feeding Activities by Bifidobacteria. Trends in Microbiology. 2018;26(4):339-350. doi: 10.1016/j.tim.2017.10.001Liu L, Fu C, Li F. Acetate affects the process of lipid metabolism in rabbit liver, skeletal muscle and adipose tissue. Animals (Basel). 2019;9(10):799. doi: 10.3390/ani9100799Liu L, Fu C, Li F. Acetate affects the process of lipid metabolism in rabbit liver, skeletal muscle and adipose tissue. Animals. 2019;9(10):799. doi: 10.3390/ani9100799Ma J, Liu Z, Gao X, et al. Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid. Pharmacol Res. 2023;189:106687. doi: 10.1016/j.phrs.2023.106687Ma J, Liu Z, Gao X, et al. Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid. Pharmacological Research. 2023;189(February):106687. doi: 10.1016/j.phrs.2023.106687Langfeld LQ, Du K, Bereswill S, Heimesaat MM. A review of the antimicrobial and immune-modulatory properties of the gut microbiota-derived short chain fatty acid propionate – What is new? Eur J Microbiol Immunol (Bp). 2021;11(2):50–56. doi: 10.1556/1886.2021.00005Langfeld LQ, Du K, Bereswill S, Heimesaat MM. A review of the antimicrobial and immune-modulatory properties of the gut microbiota-derived short chain fatty acid propionate - What is new? European Journal of Microbiology and Immunology. 2021;11(2):50-56. doi: 10.1556/1886.2021.00005Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut. Front Microbiol. 2016;7:979. doi: 10.3389/fmicb.2016.00979Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut. Frontiers in Microbiology. 2016;7(JUN):979. doi: 10.3389/fmicb.2016.00979Liu J, Zhu H, Li B, et al. Beneficial effects of butyrate in intestinal injury. J Pediatr Surg. 2020;55(6):1088–1093. doi: 10.1016/j.jpedsurg.2020.02.036Liu J, Zhu H, Li B, et al. Beneficial effects of butyrate in intestinal injury. Journal of Pediatric Surgery. 2020;55(6):1088-1093. doi: 10.1016/j.jpedsurg.2020.02.036Liu P, Wang Y, Yang G, et al. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol Res. 2021;165:105420. doi: 10.1016/j.phrs.2021.105420Liu P, Wang Y, Yang G, et al. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacological Research. 2021;165(September 2020):105420. doi: 10.1016/j.phrs.2021.105420Yao L, Davidson EA, Shaikh MW, Forsyth CB, Prenni JE, Broeckling CD. Quantitative analysis of short-chain fatty acids in human plasma and serum by GC-MS. Anal Bioanal Chem. 2022;414(15):4391–4399. doi: 10.1007/s00216-021-03785-8Yao L, Davidson EA, Shaikh MW, Forsyth CB, Prenni JE, Broeckling CD. Quantitative analysis of short-chain fatty acids in human plasma and serum by GC-MS. Analytical and Bioanalytical Chemistry. 2022;414(15):4391-4399. doi: 10.1007/s00216-021-03785-8Saha S, Day-Walsh P, Shehata E, Kroon PA. Development and validation of a lc-ms/ms technique for the analysis of short chain fatty acids in tissues and biological fluids without derivatisation using isotope labelled internal standards. Molecules. 2021;26(21):6444. doi: 10.3390/molecules26216444Garcia A, Olmo B, Lopez-Gonzalvez A, Cornejo L, Rupérez FJ, Barbas C. Capillary electrophoresis for short chain organic acids in faeces. Reference values in a Mediterranean elderly population. J Pharm Biomed Anal. 2008;46(2):356–361. doi: 10.1016/j.jpba.2007.10.026Garcia A, Olmo B, Lopez-Gonzalvez A, Cornejo L, Rupérez FJ, Barbas C. Capillary electrophoresis for short chain organic acids in faeces. Reference values in a Mediterranean elderly population. Journal of Pharmaceutical and Biomedical Analysis. 2008;46(2):356-361. doi: 10.1016/j.jpba.2007.10.026Cai J, Zhang J, Tian Y, et al. Orthogonal Comparison of GC−MS and 1 H NMR Spectroscopy for Short Chain Fatty Acid Quantitation. Anal Chem. 2017;89(15):7900–7906. doi: 10.1021/acs.analchem.7b00848Cai J, Zhang J, Tian Y, et al. Orthogonal Comparison of GC−MS and 1 H NMR Spectroscopy for Short Chain Fatty Acid Quantitation. Analitycal Chemistry. 2017;89(15):7900-7906. doi: 10.1002/hep.30150.DuctularZheng J, Zheng SJ, Cai WJ, Yu L, Yuan BF, Feng YQ. Stable isotope labeling combined with liquid chromatography-tandem mass spectrometry for comprehensive analysis of short-chain fatty acids. Anal Chim Acta. 2019;1070:51–59. doi: 10.1016/j.aca.2019.04.021Zheng J, Zheng SJ, Cai WJ, Yu L, Yuan BF, Feng YQ. Stable isotope labeling combined with liquid chromatography-tandem mass spectrometry for comprehensive analysis of short-chain fatty acids. Analytica Chimica Acta. 2019;1070:51-59. doi: 10.1016/j.aca.2019.04.021Hoving LR, Heijink M, van Harmelen V, van Dijk KW, Giera M. GC-MS analysis of short-chain fatty acids in feces, cecum content, and blood samples. Methods Mol Biol. 2018;1730:247–256. doi: 10.1007/978-1-4939-7592-1_17Hoving LR, Heijink M, van Harmelen V, van Dijk KW, Giera M. GC-MS analysis of short-chain fatty acids in feces, cecum content, and blood samples. Methods in Molecular Biology. 2018;1730:247-256. doi: 10.1007/978-1-4939-7592-1_17Dei Cas M, Paroni R, Saccardo A, et al. A straightforward LC-MS/MS analysis to study serum profile of short and medium chain fatty acids. J Chromatogr B Analyt Technol Biomed Life Sci. 2020;1154:121982. doi: 10.1016/j.jchromb.2020.121982Dei Cas M, Paroni R, Saccardo A, et al. A straightforward LC-MS/MS analysis to study serum profile of short and medium chain fatty acids. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2020;1154:1-12. doi: 10.1016/j.jchromb.2020.121982Trivedi N, Erickson HE, Bala V, Chhonker YS, Murry D. A Concise Review of Liquid Chromatography-Mass Spectrometry-Based Quantification Methods for Short Chain Fatty Acids as Endogenous Biomarkers. Int J Mol Sci. 2022;23(21):13486. doi: 10.3390/ijms232113486Trivedi N, Erickson HE, Bala V, Chhonker YS, Murry DJ. A Concise Review of Liquid Chromatography-Mass Spectrometry-Based Quantification Methods for Short Chain Fatty Acids as Endogenous Biomarkers. International Journal of Molecular Sciences. 2022;23(21):13486. doi: 10.3390/ijms232113486Primec M, Mičetić-Turk D, Langerholc T. Analysis of short-chain fatty acids in human feces: A scoping review. Anal Biochem. 2017;526:9–21. doi: 10.1016/j.ab.2017.03.007Primec M, Mičetić-Turk D, Langerholc T. Analysis of short-chain fatty acids in human feces: A scoping review. Analytical Biochemistry. 2017;526:9-21. doi: 10.1016/j.ab.2017.03.007Tumanov S, Bulusu V, Gottlieb E, Kamphorst JJ. A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis. Cancer Metab. 2016;4(1):17. doi: 10.1186/s40170-016-0157-5Tumanov S, Bulusu V, Gottlieb E, Kamphorst JJ. A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis. Cancer & Metabolism. 2016;4(1):17. doi: 10.1186/s40170-016-0157-5Kim KS, Lee Y, Chae W, Cho JY. An Improved Method to Quantify Short-Chain Fatty Acids in Biological Samples Using Gas Chromatography–Mass Spectrometry. Metabolites. 2022;12(6):525. doi: 10.3390/metabo12060525Kim KS, Lee Y, Chae W, Cho JY. An Improved Method to Quantify Short-Chain Fatty Acids in Biological Samples Using Gas Chromatography–Mass Spectrometry. Metabolites. 2022;12(6):4-15. doi: 10.3390/metabo12060525Zhang C, Tang P, Xu H, Weng Y, Tang Q, Zhao H. Analysis of Short-Chain Fatty Acids in Fecal Samples by Headspace-Gas Chromatography. Chromatographia. 2018;81:1317–1323. doi: 10.1007/s10337-018-3572-7Zhang C, Tang P, Xu H, Weng Y, Tang Q, Zhao H. Analysis of Short-Chain Fatty Acids in Fecal Samples by Headspace-Gas Chromatography. Chromatographia. 2018;81(9):1317-1323. doi: 10.1007/s10337-018-3572-7Kukaev E, Kirillova E, Tokareva A, et al. Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy. Int J Mol Sci. 2024;25(19):10636. doi: 10.3390/ijms251910636Kukaev E, Kirillova E, Tokareva A, et al. Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy. International Journal of Molecular Sciences. 2024;25(19):10636. doi: 10.3390/ijms251910636Luu M, Visekruna A. Short-chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells. Eur J Immunol. 2019;49(6):842–848. doi: 10.1002/eji.201848009Luu M, Visekruna A. Short-chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells. European Journal of Immunology. 2019;49(6):842-848. doi: 10.1002/eji.201848009Moffett JR, Puthillathu N, Vengilote R, Jaworski DM, Namboodiri AM. Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics and Oncogenesis – Part 1: Acetyl-CoA, Acetogenesis and Acyl-CoA Short-Chain Synthetases. Front Physiol. 2020;11:580167. doi: 10.3389/fphys.2020.580167Moffett JR, Puthillathu N, Vengilote R, Jaworski DM, Namboodiri AM. Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics and Oncogenesis—Part 1: Acetyl-CoA, Acetogenesis and Acyl-CoA Short-Chain Synthetases. Frontiers in Physiology. 2020;11(November):580167. doi: 10.3389/fphys.2020.580167Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation. Mol Cell. 2012;48(4):611–626. doi: 10.1016/j.molcel.2012.08.033Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation. Molecular Cell. 2012;48(4):611-626. doi: 10.1016/j.molcel.2012.08.033.TheBaldassarre ME, Di Mauro A, Capozza M, et al. Dysbiosis and prematurity: Is there a role for probiotics? Nutrients. 2019;11(6):1273. doi: 10.3390/nu11061273Zhao J, Hu J, Ma X. Sodium caprylate improves intestinal mucosal barrier function and antioxidant capacity by altering gut microbial metabolism. Food Funct. 2021;12(20):9750–9762. doi: 10.1039/d1fo01975aZhao J, Hu J, Ma X. Sodium caprylate improves intestinal mucosal barrier function and antioxidant capacity by altering gut microbial metabolism. Food and Function. 2021;12(20):9750-9762. doi: 10.1039/d1fo01975aLevy M, Thaiss CA, Zeevi D, et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell. 2015;163(6):1428–1443. doi: 10.1016/j.cell.2015.10.048Levy M, Thaiss CA, Zeevi D, et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell. 2015;163(6):1428-1443. doi: 10.1002/hep.30150.DuctularTian P, Yang W, Guo X, et al. Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis. Nat Commun. 2023;14(1):1710. doi: 10.1038/s41467-023-37419-7Tian P, Yang W, Guo X, et al. Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis. Nature Communications. 2023;14(1):1710. doi: 10.1038/s41467-023-37419-7Beisner J, Filipe Rosa L, Kaden-Volynets V, Stolzer I, Günther C, Bischoff SC. Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides. Front Immunol. 2021;12:678360. doi: 10.3389/fimmu.2021.678360Beisner J, Filipe Rosa L, Kaden-Volynets V, Stolzer I, Günther C, Bischoff SC. Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides. Frontiers in Immunology. 2021;12(June):678360. doi: 10.3389/fimmu.2021.678360van der Hee B, Wells JM. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol. 2021;29(8):700–712. doi: 10.1016/j.tim.2021.02.001van der Hee B, Wells JM. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends in Microbiology. 2021;29(8):700-712. doi: 10.1016/j.tim.2021.02.001Schulthess J, Pandey S, Capitani M, et al. The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity. 2019;50(2):432–445.e7. doi: 10.1016/j.immuni.2018.12.018Schulthess J, Pandey S, Capitani M, et al. The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity. 2019;50(2):432-445.e7. doi: 10.1016/j.immuni.2018.12.018Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282–1286. doi: 10.1038/nature08530Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282-1286. doi: 10.1038/nature08530Thomas SP, Denu JM. Short-chain fatty acids activate acetyltransferase p300. Elife. 2021;10:e72171. doi: 10.7554/eLife.72171Thomas SP, Denu JM. Short-chain fatty acids activate acetyltransferase p300. eLife. 2021;10:e72171. doi: 10.7554/eLife.72171Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–450. doi: 10.1038/nature12721Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446-450. doi: 10.1038/nature12721Sun M, Wu W, Chen L, et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9(1):3555. doi: 10.1038/s41467-018-05901-2Sun M, Wu W, Chen L, et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nature Communications. 2018;9(1):3555. doi: 10.1038/s41467-018-05901-2Kim M, Qie Y, Park J, Kim CH. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host Microbe. 2016;20(2):202–214. doi: 10.1016/j.chom.2016.07.001Kim M, Qie Y, Park J, Kim CH. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host and Microbe. 2016;20(2):202-214. doi: 10.1016/j.chom.2016.07.001Kumar M, Singh P, Murugesan S, et al. Microbiome as an Immunological Modifier. Methods Mol Biol. 2020;2055:595–638. doi: 10.1007/978-1-4939-9773-2_27Kumar M, Singh P, Murugesan S, et al. Microbiome as an Immunological Modifier. Methods in Molecular Biology. 2020;2055(1):595-638. doi: 10.1007/978-1-4939-9773-2Sorbara MT, Dubin K, Littmann ER, et al. Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification. J Exp Med. 2019;216(1):84–98. doi: 10.1084/jem.20181639Sorbara MT, Dubin K, Littmann ER, et al. Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification. Journal of Experimental Medicine. 2019;216(1):84-98. doi: 10.1084/jem.20181639Byndloss MX, Olsan EE, Rivera-Chávez F, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science. 2017;357(6351):570–575. doi: 10.1126/science.aam9949Byndloss MX, Olsan EE, Rivera-Chávez F, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science. 2017;357(6351):570-575. doi: 10.1126/science.aam9949Fundora JB, Guha P, Shores DR, Pammi M, Maheshwari A. Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria. Pediatr Res. 2020;87(2):235–248. doi: 10.1038/s41390-019-0482-9Fundora JB, Guha P, Shores DR, Pammi M, Maheshwari A. Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria. Pediatric Research. 2020;87(2):235-248. doi: 10.1038/s41390-019-0482-9Jilling T, Simon D, Lu J, et al. The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis. J Immunol. 2006;177(5):3273–3282. doi: 10.4049/jimmunol.177.5.3273Jilling T, Simon D, Lu J, et al. The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis. Journal of Immunology. 2006;177(5):3273-3282. doi: 10.4049/jimmunol.177.5.3273Waligora-Dupriet AJ, Dugay A, Auzeil N, Huerre M, Butel MJ. Evidence for clostridial implication in necrotizing enterocolitis through bacterial fermentation in a gnotobiotic quail model. Pediatr Res. 2005;58(4):629–635. doi: 10.1203/01.PDR.0000180538.13142.84Waligora-Dupriet AJ, Dugay A, Auzeil N, Huerre M, Butel MJ. Evidence for clostridial implication in necrotizing enterocolitis through bacterial fermentation in a gnotobiotic quail model. Pediatric Research. 2005;58(4):629-635. doi: 10.1203/01.PDR.0000180538.13142.84Alsharairi NA. Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis. Life (Basel). 2023;13(2):561. doi: 10.3390/life13020561Alsharairi NA. Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis. Life. 2023;13(2):561. doi: 10.3390/life13020561Athalye-Jape G, Esvaran M, Patole S, et al. Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial. BMJ Open Gastroenterol. 2022;9(1):e000811. doi: 10.1136/bmjgast-2021-000811Athalye-Jape G, Esvaran M, Patole S, et al. Effect of single versus multistrain probiotic in extremely preterm infants: A randomised trial. BMJ Open Gastroenterology. 2022;9(1):e000811. doi: 10.1136/bmjgast-2021-000811Neumann CJ, Mahnert A, Kumpitsch C, et al. Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine. Nat Commun. 2023;14(1):1349. doi: 10.1038/s41467-023-36825-1Neumann CJ, Mahnert A, Kumpitsch C, et al. Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine. Nature Communications. 2023;14(1):1349. doi: 10.1038/s41467-023-36825-1Frau A, Lett L, Slater R, et al. The stool volatile metabolome of pre-term babies. Molecules. 2021;26(11):3341. doi: 10.3390/molecules26113341Wang C, Shoji H, Sato H, et al. Effects of oral administration of Bifidobacterium breve on fecal lactic acid and short-chain fatty acids in low birth weight infants. J Pediatr Gastroenterol Nutr. 2007;44(2):252–257. doi: 10.1097/01.mpg.0000252184.89922.5fWang C, Shoji H, Sato H, et al. Effects of oral administration of Bifidobacterium breve on fecal lactic acid and short-chain fatty acids in low birth weight infants. Journal of Pediatric Gastroenterology and Nutrition. 2007;44(2):252-257. doi: 10.1097/01.mpg.0000252184.89922.5fXiong J, Liao XS, Yin T, Liu XC, Bao L, Li LQ. Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study. Front Cell Infection Microbiol. 2022;12:1030588. doi: 10.3389/fcimb.2022.1030588Xiong J, Liao XS, Yin T, Liu XC, Bao L, Li LQ. Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study. Frontiers in Cellular and Infection Microbiology. 2022;12(November):1030588. doi: 10.3389/fcimb.2022.1030588Huang H, Peng Q, Zhang Y, et al. Abnormalities in microbial composition and function in infants with necrotizing enterocolitis: A single-center observational study. Front Pediatr. 2022;10:963345. doi: 10.3389/fped.2022.963345Huang H, Peng Q, Zhang Y, et al. Abnormalities in microbial composition and function in infants with necrotizing enterocolitis: A single-center observational study. Frontiers in Pediatrics. 2022;10(October):963345. doi: 10.3389/fped.2022.963345Casaburi G, Wei J, Kazi S, et al. Metabolic model of necrotizing enterocolitis in the premature newborn gut resulting from enteric dysbiosis. Front Pediatr. 2022;10:893059. doi: 10.3389/fped.2022.893059Casaburi G, Wei J, Kazi S, et al. Metabolic model of necrotizing enterocolitis in the premature newborn gut resulting from enteric dysbiosis. Frontiers in Pediatrics. 2022;10(August):893059. doi: 10.3389/fped.2022.893059Pourcyrous M, Nolan VG, Goodwin A, Davis SL, Buddington RK. Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula. J Pediatr Gastroenterol Nutr. 2014;59(6):725–731. doi: 10.1097/MPG.0000000000000515Pourcyrous M, Nolan VG, Goodwin A, Davis SL, Buddington RK. Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula. Journal of Pediatric Gastroenterology and Nutrition. 2014;59(6):725-731. doi: 10.1097/MPG.0000000000000515Cifuentes MP, Chapman JA, Stewart CJ. Gut microbiome derived short chain fatty acids: Promising strategies in necrotising enterocolitis. Curr Res Microb Sci. 2024;6:100219. doi: 10.1016/j.crmicr.2024.100219Cifuentes MP, Chapman JA, Stewart CJ. Gut microbiome derived short chain fatty acids: Promising strategies in necrotising enterocolitis. Current Research in Microbial Sciences. 2024;6(January):100219. doi: 10.1016/j.crmicr.2024.100219Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace N. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–13785. doi: 10.1073/pnas.0706625104Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(34):13780-13785. doi: 10.1073/pnas.0706625104Sokol H, Seksik P, Furet JP, et al. Low counts of faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15(8):1183–1189. doi: 10.1002/ibd.20903Sokol H, Seksik P, Furet JP, et al. Low counts of faecalibacterium prausnitzii in colitis microbiota. Inflammatory Bowel Diseases. 2009;15(8):1183-1189. doi: 10.1002/ibd.20903Waligora-Dupriet AJ, Dugay A, Auzeil N, et al. Short-chain fatty acids and polyamines in the pathogenesis of necrotizing enterocolitis: Kinetics aspects in gnotobiotic quails. Anaerobe. 2009;15(4):138–144. doi: 10.1016/j.anaerobe.2009.02.001Waligora-Dupriet AJ, Dugay A, Auzeil N, et al. Short-chain fatty acids and polyamines in the pathogenesis of necrotizing enterocolitis: Kinetics aspects in gnotobiotic quails. Anaerobe. 2009;15(4):138-144. doi: 10.1016/j.anaerobe.2009.02.001Lin J, Nafday SM, Chauvin SN, et al. Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats. J Pediatr Gastroenterol Nutr. 2002;35(4):545–550. doi: 10.1097/00005176-200210000-00016Lin J, Nafday SM, Chauvin SN, et al. Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats. Journal of Pediatric Gastroenterology and Nutrition. 2002;35(4):545-550. doi: 10.1097/00005176-200210000-00016Nafday SM, Chen W, Peng L, Babyatsky MW, Holzman IR, Lin J. Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages. Pediatr Res. 2005;57(2):201–204. doi: 10.1203/01.PDR.0000150721.83224.89Nafday SM, Chen W, Peng L, Babyatsky MW, Holzman IR, Lin J. Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages. Pediatric Research. 2005;57(2):201-204. doi: 10.1203/01.PDR.0000150721.83224.89Thymann T, Møller HK, Stoll B, et al. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs. Am J Physiol Gastrointest Liver Physiol. 2009;297(6):G1115–G1125. doi: 10.1152/ajpgi.00261.2009Thymann T, Møller HK, Stoll B, et al. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2009;297(6):1115-1125. doi: 10.1152/ajpgi.00261.2009Kien CL. Digestion, absorption, and fermentation of carbohydrates in the newborn. Clin Perinatol. 1996;23(2):211–228. doi: 10.1016/s0095-5108(18)30239-2Kien CL. Digestion, absorption, and fermentation of carbohydrates in the newborn. Clinics in Perinatology. 1996;23(2):211-228. doi: 10.1016/s0095-5108(18)30239-2Peng L, He Z, Chen W, Holzman IR, Lin J. Effects of butyrate on intestinal barrier function in a caco-2 cell monolayer model of intestinal barrier. Pediatr Res. 2007;61(1):37–41. doi: 10.1203/01.pdr.0000250014.92242.f3Peng L, He Z, Chen W, Holzman IR, Lin J. Effects of butyrate on intestinal barrier function in a caco-2 cell monolayer model of intestinal barrier. Pediatric Research. 2007;61(1):37-41. doi: 10.1203/01.pdr.0000250014.92242.f3Vieira ELM, Leonel AJ, Sad AP, et al. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J Nutr Biochem. 2012;23(5):430–436. doi: 10.1016/j.jnutbio.2011.01.007Vieira ELM, Leonel AJ, Sad AP, et al. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. Journal of Nutritional Biochemistry. 2012;23(5):430-436. doi: 10.1016/j.jnutbio.2011.01.007