Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Abstract

Objective: To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables.

Study design: We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony-forming units daily) or placebo for 42 days and followed for 134 days.

Results: Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm3), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms.

Conclusions: Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks.

Trial registration: ClinicalTrials.gov: NCT01849991.

Keywords: Barr diary; crying; immunology; infant; microbiome; neutropenia; regulatory T cells.

Copyright © 2017 Elsevier Inc. All rights reserved.

Figures

Figure 1:

Participant Consort Diagram

Figure 2:

Absolute neutrophil count (ANC) from baseline to 42 days in the participants receiving LR or placebo (P). Dotted line indicates ANC = 1,500, traditionally representing higher risk of infection in pediatric patients.

Figure 3:

Changes in relative abundance of prominent genera over time in infants treated (blue) and infants give a placebo (orange). Each thin line represents a single infant. The mean for treated and placebo infants is represented by bold lines of the corresponding color. Only infants that had baseline (BL) and 4th visit (V4) specimens are represented in the graph.