Efficacy of a Limosilactobacillus reuteri DSM 17938 and BG-R46® Formulation in Predominantly Breastfed Infants with Infant Distress Syndrome: A Randomized Double-Blind Placebo-Controlled Trial

Background: Infant distress syndrome, previously termed Infantile colic, is a common disorder of gut–brain interaction characterized by excessive crying and impaired behavioral regulation. Although Limosilactobacillus reuteri DSM 17938 has shown efficacy in predominantly breastfed infants, treatment responses remain variable, highlighting the need to investigate alternative probiotic formulations. BG-R46™, a strain derived from DSM 17938, exhibits distinct properties in preclinical models, providing a rationale for evaluating the combined formulation. This study investigated the efficacy and tolerability of DSM 17938 plus BG-R46™ compared with placebo in infants with infantile colic. Methods: In this randomized, double-blind, placebo-controlled trial, 50 infants were randomized to receive either the probiotic formulation or placebo for 21 days. Forty-eight infants (24 per group) were included in the intention-to-treat and per-protocol analyses. The primary endpoint was the change from baseline to Day 7 in total infant distress time, defined as the sum of awake fussing, crying, and inconsolable crying recorded using the Baby’s Day Diary®. Secondary outcomes included crying time, infant behavioral regulation (sleep duration, awake and content behavior, awake fussing, and inconsolable crying), maternal emotional well-being assessed using the Edinburgh Postnatal Depression Scale (EPDS), and safety. Results: Baseline infant distress time was comparable between groups. At Day 7, infant distress time decreased by 43% in the probiotic group versus 13% in the placebo group (−236.0 ± 111.5 vs. −66.7 ± 100.1 min/day; p < 0.001). At Day 21, reductions reached 62% and 26%, respectively. The probiotic formulation was well tolerated throughout the study. Conclusions: Supplementation with L. reuteri DSM 17938 plus L. reuteri BG-R46™ significantly reduced infant distress compared with placebo.