Gut Microbiota and Short-Chain Fatty Acids in the Pathogenesis of Necrotizing Enterocolitis in Very Preterm Infants - Review

Sep 28, 2026

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The development of a symbiotic gut ecosystem is essential for postnatal adaptation, yet very preterm infants show an unstable microbiome with reduced diversity and a dominance of Gram-negative Proteobacteria, increasing necrotizing enterocolitis (NEC) risk. Short-chain fatty acids (SCFAs) act as key bacterial metabolites supporting intestinal homeostasis, immune development, barrier integrity, and reduced inflammation. This review analyzes microbiota and SCFAs in neonatal NEC, summarizing clinical and experimental evidence and outlining directions for diagnostics and therapeutic approaches.

LanguageEnglish

CategoryHealthcare

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Pages14

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Introduction

REVIEWS Gut Microbiota and Short-Chain Fatty Acids in the Pathogenesis of Necrotizing Enterocolitis in Very Preterm Infants E. N. Kukaev 1,2* , A. O. Tokareva 1 , O. A. Krogh-Jensen 1,3 , A. A. Lenyushkina 1 , N. L. Starodubtseva 1,4 1National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, 117997 Russia 2V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, 119991 Russia 3Federal 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), Moscow, 119048 Russia 4Moscow Institute of Physics and Technology, Dolgoprudny, Moscow region, 141701 Russia *E-mail: [e_kukaev@oparina4.ru](e_kukaev@oparina4.ru) Received January 29, 2025; in final form, June 25, 2025 DOI: 10.32607/actanaturae.27623 Copyright © 2025 National Research University Higher School of Economics. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT 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, anda 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 SCFAsin 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. KEYWORDS necrotizing enterocolitis, very premature infants, diagnostics, gas chromatography-mass spectrometry, short-chain fatty acids, gut microbiota. ABBREVIATIONS GC – gas-chromatography; LC – liquid-chromatography; SCFA – short-chain fatty acids; MS – mass-spectrometry; NEC – necrotizing enterocolitis; NICU – neonatal intensive care unit; PCR – polymerase chain reaction. INTRODUCTION Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects newborns. It is characterized by marked inflammation of the intestinal wall, followed by necrosis and potential perforation. NECis a significant gastrointestinal complication that primarily affects premature infants, with rare instances reported in infants born after 32 weeks gestation [1]. The primary factors that predispose to excessive gut inflammation include gastrointestinal immaturity, impaired bacterial colonization, and the lack of enteral feeding with breast milk [2] . The incidence of NEC is inversely proportional to gestational age, ranging from 2% to 10% in very preterm infants (28–32 weeks of gestation) and reaching 55% among extremely preterm newborns [3]. Notwithstanding the progress achieved in modern medicine, the incidence of NEC has not changed substantially over time in very low birth weight (VLBW) infants and constitutes a major cause of adverse outcomes in this cohort. The need for surgical int

FAQs

Why are very preterm infants at higher risk of necrotizing enterocolitis (NEC)?

They exhibit an overall unstable gut ecosystem with reduced microbial diversity and predominance of Gram-negative Proteobacteria, factors linked to increased NEC risk.

What roles do short-chain fatty acids (SCFAs) play in neonatal intestinal health?

SCFAs are essential for maintaining intestinal homeostasis, supporting immune development, enhancing intestinal barrier integrity, and reducing inflammation.

How might SCFAs contribute to NEC diagnostics and therapy?

Clinical studies show decreased total SCFA levels and individual bacterial metabolites in infants with NEC, and the review emphasizes assessing diagnostic utility and feasibility of pro- and postbiotic formulations using multi-center multi-omics research.

Sep 28, 2026

Uploaded by acoobca