Microbial Interactions with Protein Intake and Preterm Infant Body Composition: Secondary Analysis of a Randomized Trial.

Publication Title

The Journal of nutrition

Document Type

Article

Publication Date

9-1-2026

Keywords

Humans; Body Composition; Dietary Proteins; Infant, Newborn; Infant, Premature; Female; Male; Gastrointestinal Microbiome; Dietary Supplements; Enteral Nutrition; body composition; microbiome; nutrition; prematurity; protein.; washington; isb

Abstract

BACKGROUND: Enteral protein supplementation improves preterm infant growth and may impact body composition and the gut microbiota.

OBJECTIVES: This study aimed to identify the effects of additional enteral protein supplementation on the gut microbiota and microbial and clinical drivers of body composition.

METHODS: Secondary analysis of a masked randomized trial of additional enteral protein vs. standard fortification in preterm infants born at 25 to 28 weeks of gestation (NCT03586102) was conducted. Stool samples at weeks 4 and 8 underwent 16S rRNA sequencing; functional potential was predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2). Body composition was measured by air-displacement plethysmography at 36 wk postmenstrual age (PMA). Least absolute shrinkage and selection operator (LASSO) regression with multivariable linear regression identified body composition predictors.

RESULTS: Among 46 infants, gestational age (P = 0.16) and sex (P = 0.55) did not differ between groups. The protein group had higher week 4 Shannon diversity than standard fortification (median 1.2 vs. 0.87, P = 0.049). Week 4 Shannon diversity was positively correlated with fat-free mass z-score at 36 wk PMA (r

CONCLUSIONS: Additional protein supplementation is associated with fat-free mass z-score and alterations to the gut microbiota. Clinical variables and microbial variables are key predictors of body composition, suggesting that nutrition, clinical factors, and the gut microbiota jointly contribute to body composition in extremely preterm infants. This study was registered at clinicaltrials.gov as NCT03586102 https://clinicaltrials.gov/study/NCT03586102 (registered in March 2020).

Area of Special Interest

Women & Children

Area of Special Interest

Digestive Health

Specialty/Research Institute

Pediatrics

Specialty/Research Institute

Perinatology/Neonatology

Specialty/Research Institute

Gastroenterology

DOI

10.1016/j.tjnut.2026.101723

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