Regulatory T cells and Toll-like receptor 2 and 4 mRNA expression in infants with colic treated with Lactobacillus reuteri DSM17938

Abstract

Regulatory T cells induce immune homeostasis and the expression of Toll like receptors (TLRs); subsequent inflammatory cytokine release may be involved. Recent studies have shown a microbial imbalance in the gut of colicky infants (with a prevalence of gram-negative bacteria, such as Escherichia coli), and accumulating evidence has shown the efficacy of a probiotic (Lactobacillus reuteri) in breastfed subjects, but the underlying mechanism remains undefined. The study enrolled 59 infants younger than 60 days, of whom 34 subjects had colic and 25 were healthy controls. With a double-blind, placebo-controlled randomised study performed in our unit from October 2016 to July 2017, infants with colic were randomly assigned to receive oral daily L. reuteri DSM17938 (1×108 cfu) or placebo for 28 days. Peripheral blood was collected to assess the expression of FoxP3, TLR2 and TLR4 mRNA using real-time TaqMan RT-PCR at baseline and after the study period. Our findings showed increased mRNA expression of the transcription factor forkhead box P3 (FoxP3) in infants treated with L. reuteri DSM 17938 for 28 days (P<0.009) and increased TLR2 and TLR4 mRNA expression in both treated and placebo subjects. After L. reuteri administration for 28 days in infants with colic, we observed a significant decrease in daily crying time (302.3±19.86 min/day on day 0 vs 76.75±22.15 min/day on day 28, P=0.001). This study provides evidence that the observed increase in FoxP3 expression and reduction in crying time might be responses to probiotic treatment, while the increase in TLR2 and TLR4 mRNA expression might be related to age. Exploiting these new findings may lead to an unprecedented level of therapeutic control over immune tolerance using probiotics.

The Effect of Probiotics on Symptoms, Gut Microbiota and Inflammatory Markers in Infantile Colic: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials

“…Ultimately 16 studies were included [19,[33][34][35][45][46][47][48][49][50][51][52][53][54][55][56], the majority of which (n = 7) were conducted in Italy [19,33,45,46,49,50,54]. Intervention sponsorship was not specified for seven studies [19,45,47,48,50,51,53] and two trials [46,52] were financed by governmental institutions.…”

“…Ultimately 16 studies were included [19,[33][34][35][45][46][47][48][49][50][51][52][53][54][55][56], the majority of which (n = 7) were conducted in Italy [19,33,45,46,49,50,54]. Intervention sponsorship was not specified for seven studies [19,45,47,48,50,51,53] and two trials [46,52] were financed by governmental institutions. There were 14 double-blinded studies [19,34,35,[45][46][47][48][49][50][51][52][54][55][56], one single-blinded [53] and in one review, the blinding was not specified [33].…”

“…Intervention sponsorship was not specified for seven studies [19,45,47,48,50,51,53] and two trials [46,52] were financed by governmental institutions. There were 14 double-blinded studies [19,34,35,[45][46][47][48][49][50][51][52][54][55][56], one single-blinded [53] and in one review, the blinding was not specified [33]. The duration of probiotic therapy was: median = 28 days, interquartile range (IQR) = 8 days, range = 14 to 90 days.…”

“…The duration of probiotic therapy was: median = 28 days, interquartile range (IQR) = 8 days, range = 14 to 90 days. The primary probiotic strain utilized in the included studies was Lactobacillus reuteri Deutsche Sammlung von Mikroorganismen (German Collection of Microorganisms; DSM) strain 17938 (n = 9) [19,[33][34][35]47,49,50,52,53,56]. Other probiotic strains were: Bifidobacterium breve BR03 (DSM16604) and B632 (DSM24706) (…”

“…The numbers of males and females were similar (males = 52.73%). In a majority of studies (n = 13) [19,[33][34][35][46][47][48][49][50][51]53,55,56], infantile colic was diagnosed based on Wessel's or modified-Wessel's criteria. In one study, the Rome IV criteria were utilized [45], in one trial Rome III criteria [54] were used, and in one trial parental diaries were used for colic diagnoses [52].…”