Longitudinal Fecal Short-Chain Fatty Acid Trajectories in Preterm Infants with Early-Onset Neonatal Sepsis: A Pilot Study

Evgenii Kukaev ^1,2,3, Olga Krogh-Jensen ^1,4, Natalia Starodubtseva ^1,3

⁰V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia.

Life (basel, Switzerland) +

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December 30, 2025

View abstract on PubMed

Summary

Early-onset neonatal sepsis (EONS) in preterm infants is linked to early gut metabolic changes. Fecal short-chain fatty acids (SCFAs) show reduced acetic acid and increased other acids, indicating gut involvement in infection.

Area Of Science

Neonatal Medicine
Microbiome Research
Metabolomics

Background

Early-onset neonatal sepsis (EONS) is a critical threat to preterm infants.
The gut microbiome's role in EONS is increasingly recognized.
Fecal short-chain fatty acids (SCFAs) offer a potential non-invasive marker for inflammatory vulnerability.

Purpose Of The Study

To characterize the temporal changes in fecal SCFAs during EONS in preterm infants.
To investigate the relationship between SCFA profiles and EONS development.
To explore SCFAs as potential biomarkers for early detection of EONS.

Main Methods

Pilot prospective longitudinal cohort study of 49 preterm infants at high risk for necrotizing enterocolitis (NEC).
Serial stool sample collection at multiple timepoints from birth up to 28 days of life.
Gas chromatography-mass spectrometry (GC-MS) analysis of 12 SCFAs, including branched-chain fatty acids (BCFAs) and medium-chain fatty acids (MCFAs).
Evaluation of absolute concentrations, relative fractions, and ratio-based metrics, with PLS-DA for group discrimination.

Main Results

Infants with EONS showed distinct early SCFA profile changes at ~3 days of life.
Significantly lower relative fraction of acetic acid and enrichment of non-acetate SCFAs (e.g., propionic, valeric, BCFAs) were observed in EONS.
Ratio-based metrics (e.g., acetic/propionic) were markedly reduced in EONS, indicating a shift from acetate dominance.
Partial separation between EONS and non-sepsis groups was achieved using PLS-DA at the earliest timepoint, driven by SCFA alterations.

Conclusions

EONS is associated with early, structured alterations in fecal SCFA profiles in preterm infants.
Dynamic, ratio-based SCFA assessment is more informative than absolute concentrations for detecting transient metabolic signatures of infection.
These findings highlight the gut's metabolic involvement in EONS and support further research for refining early risk stratification in high-risk neonates.

Keywords:

early-onset neonatal sepsis (EONS) ecrotizing enterocolitis (NEC) gas chromatography–mass spectrometry (GC–MS) gut microbial metabolism intestinal vulnerability longitudinal analysis neonatal biomarkers preterm infants short-chain fatty acids (SCFAs)

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