Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial.

Francesco Savino, Maria Garro, Paola Montanari, Ilaria Galliano, Massimiliano Bergallo

Journal: The Journal of pediatrics 2017;192():171-177.e1

PMID: 28969887

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Plain Language Summary

The causes of infant colic are unknown, but growing evidence shows a possible link with the gut microbiome. Increased inflammation has also been found in infants with colic, and this could be linked to dysbiosis. This double-blind, placebo-controlled clinical trial investigated whether supplementation with the probiotic Lactobacillus reuteri (L reuteri) DSM 17938 could reduce the crying time and modify inflammation in a group of infants with colic. Infants enrolled in the trial were less than 12 weeks old, with a healthy birth weight and predominantly breastfed. Infants with colic were given either 5 million colony-forming units (CFU) of L reuteri DSM 17938 or a placebo daily for 1 month. Crying times were significantly shortened among infants with colic given the probiotic, whilst the concentration of transcription factors for cells that help to regulate the immune system increased significantly. Infants treated with the probiotic showed an increase in the percentage of Lactobacillus and a decrease in the inflammatory marker faecal calprotectin. The authors concluded that their findings support the hypothesis that dysbiosis and inflammation may contribute to the onset of infant colic.

Abstract

OBJECTIVES

To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic.

STUDY DESIGN

A double-blind, placebo-controlled randomized trial was conducted in primary care in Torino from August 1, 2015 to September 30, 2016. Patients suffering from infantile colic were randomly assigned to receive daily oral L reuteri (1 × 10 colony forming unit) or placebo for 1 month. Daily crying times were recorded in a structured diary. FOXP3 and RORγ messenger RNA in the peripheral blood was assessed with real-time TaqMan reverse transcription polymerase chain reaction. Gut microbiota and fecal calprotectin were evaluated.

RESULTS

After infants with colic were supplemented with L reuteri DSM 17938 for 30 days, crying times were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (74.67 ± 25.04 [IQR = 79] minutes /day vs 147.85 [IQR = 135] minutes /day [P = .001]). The FOXP3 concentration increased significantly (P = .009), resulting in decreased RORγ/FOXP3 ratios: 0.61 (IQR = 0.60) at day 0 and 0.48 (IQR = 0.28) at day 30 (P = .028). Furthermore, the probiotic increased the percentage of Lactobacillus (P = .049) and decreased fecal calprotectin (P = .0001).

CONCLUSIONS

Infants with colic treated with L reuteri for 30 days had a significantly decreased crying time and an increased FOXP3 concentration, resulting in a decreased RORγ/FOXP3 ratio. The treatment reduced fecal calprotectin.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT00893711.

Address: Department of Pediatrics, Universitary Hospital Città della Salute e della Scienza di Torino, Turin, Italy. Electronic address: [email protected].; Department of Pediatrics, Universitary Hospital Città della Salute e della Scienza di Torino, Turin, Italy.; Department of Public Health and Pediatric Sciences, University of Turin, School of Medicine, Turin, Italy.

DOI: 10.1016/j.jpeds.2017.08.062