Synbiotic supplementation leads to gut microbiome communities with functional capacity linked to better brain white matter development in preterm infants

Preterm birth, a major cause of brain injury, is often linked to dysregulated gut microbiome development. This association underscores microbial metabolic function as a modifiable target to support neurodevelopment. In this secondary analysis of data derived from a randomized controlled trial (Trial Registration: ISRCTN96620855), we tested whether daily nutritional supplementation with Bifidobacterium breve M-16V, short- and long-chain oligosaccharides, and L-glutamine could steer the gut microbiome of very and extremely preterm infants toward communities that support brain maturation. The gut microbiome was profiled with longitudinal shotgun metagenomics at nine time points during the intervention, which started at 48–72 h after birth and continued until 36 weeks postmenstrual age. Additionally, MRI scans were conducted when infants reached term-equivalent age to evaluate brain maturation. Supplementation promoted the early establishment of Bifidobacterium-rich communities in the test group, with enhanced capacity for amino acid biosynthesis and pyruvate fermentation towards acetate and lactate production. Integration of microbiome data with brain developmental markers post hoc showed that the same functions were markedly reduced in infants with delayed white-matter myelination. By integrating microbiome functional capacity profiling and evaluation of brain maturation via MRI, this study demonstrated that early microbial modulation could influence brain development, positioning the preterm gut microbiome as a clinically actionable target.

Authors

Institutions

Publication Details

Journal
Gut Microbes
Published
2026-10-07
DOI
https://doi.org/10.1080/19490976.2026.2743949
Primary Topic
Infant Nutrition and Health
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Synbiotic supplementation leads to gut microbiome communities with functional capacity linked to better brain white matter development in preterm infants

Harm Wopereis, Monique van de Lagemaat, Marta Kozior, Clemens B. Meijssen et al.
Gut Microbes
Infant Nutrition and Health
article

Synbiotic supplementation leads to gut microbiome communities with functional capacity linked to better brain white matter development in preterm infants

Harm Wopereis, Monique van de Lagemaat, Marta Kozior, Clemens B. Meijssen, Károly Illy, Lisa M. Hortensius, Niek E. van der Aa, Clara Belzer, Lidewij Schipper, Jeroen Dudink, Sandra Drost‐Verhoef, Caroline G. M. de Theije, Jan Knol, Charlie C. Obihara, Inge P. de Boer, Annelies Hennink, Ivana Išgum, Els Janson, Johanna H. Oudshoorn, Anna Voulgari‐Kokota, Floris Groenendaal, Max A. Viergever, R Van Elburg, Sudarshan Shetty, Manon Benders, Nathalie Claessens, Frank van Bel, Carin M. Dassel, Ineke Heikamp de Jong, Jacqueline L. A. M. van Hillegersberg-Schilder, Annemieke Wildt-Grootendorst
article en

Abstract

Preterm birth, a major cause of brain injury, is often linked to dysregulated gut microbiome development. This association underscores microbial metabolic function as a modifiable target to support neurodevelopment. In this secondary analysis of data derived from a randomized controlled trial (Trial Registration: ISRCTN96620855), we tested whether daily nutritional supplementation with Bifidobacterium breve M-16V, short- and long-chain oligosaccharides, and L-glutamine could steer the gut microbiome of very and extremely preterm infants toward communities that support brain maturation. The gut microbiome was profiled with longitudinal shotgun metagenomics at nine time points during the intervention, which started at 48–72 h after birth and continued until 36 weeks postmenstrual age. Additionally, MRI scans were conducted when infants reached term-equivalent age to evaluate brain maturation. Supplementation promoted the early establishment of Bifidobacterium-rich communities in the test group, with enhanced capacity for amino acid biosynthesis and pyruvate fermentation towards acetate and lactate production. Integration of microbiome data with brain developmental markers post hoc showed that the same functions were markedly reduced in infants with delayed white-matter myelination. By integrating microbiome functional capacity profiling and evaluation of brain maturation via MRI, this study demonstrated that early microbial modulation could influence brain development, positioning the preterm gut microbiome as a clinically actionable target.

Gut MicrobesVol. 18(1)
Utrecht University (NL), Gelre Hospitals (NL), University Medical Center Utrecht (NL), Emma Kinderziekenhuis (NL), St. Antonius Ziekenhuis (NL), Diakonessenhuis hospital (NL), Ziekenhuis Rivierenland (NL), Elisabeth-TweeSteden Ziekenhuis (NL), Amsterdam University Medical Centers (NL), Deventer Ziekenhuis (NL), Meander Medisch Centrum (NL), Wilhelmina Children's Hospital (NL), University of Amsterdam (NL), Wageningen University & Research (NL)
Openalex Percentile: Top 12%
Infant Nutrition and Health
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.