Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis

Abstract

Introduction: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx^®, Visbiome^®, DeSimone Formulation^®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo.

Methods: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426).

Results: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported.

Conclusions: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.

Keywords: infantile colic; metabolomics; microbiota; probiotics.

Figure 1

Study flow.

Figure 2

Lactobacilli concentration in feces of placebo (pbo)- and probiotics (prob)-supplemented infants.

Figure 3

rPCA model built on the space, constituted by the concentration of the molecules listed in Table 4. In the scoreplot (A), samples from people treated with the placebo and the probiotics are represented with squares and circles respectively. The wide, empty circles represent the median of the samples at the various time-points. Samples at T0 from the two groups are superimposed. In the barplot (B), describing the correlation between the concentration of each molecule and its importance over PC 2, gray bars highlight statistically significant correlations (p < 0.05).