Publication Date

10-7-2022

Journal

BMC Pediatrics

DOI

10.1186/s12887-022-03647-x

PMID

36207675

PMCID

PMC9541012

PubMedCentral® Posted Date

10-7-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Cattle, Colic, Double-Blind Method, Female, Gastrointestinal Microbiome, Humans, Infant Formula, Infant, Newborn, Lacticaseibacillus rhamnosus, Leukocyte L1 Antigen Complex, Pilot Projects, Probiotics, Prospective Studies, RNA, Ribosomal, 16S, Brain-gut axis, Calprotectin, Colic, Infant, Infant formula, Lactocaseibacillus rhamnosus GG, Microbiome, Partially hydrolyzed protein, Probiotics

Abstract

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with added LGG (PHF-LGG, n = 36). Parent-reported infant behavior was recorded at three time points (Study Days 2-4, 10-12, and 18-20). Duration (hours/day) of crying/fussing (averaged over each three-day period) was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19-21) to determine stool LGG colonization (by qPCR) and microbial abundance (using 16S rRNA gene sequencing) and calprotectin (μg/g).

RESULTS: Duration of crying/fussing (mean ± SE) decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline.

CONCLUSIONS: In this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome.

TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT02340143. Registered 16/01/2015.

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