Article

Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial

Department of Pediatrics, Regina Margherita Children Hospital, University of Turin, Piazza Polonia, 94 10126 Turin, Italy.
PEDIATRICS (Impact Factor: 5.3). 09/2010; 126(3):e526-33. DOI: 10.1542/peds.2010-0433
Source: PubMed

ABSTRACT To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota.
Fifty exclusively breastfed colicky infants, diagnosed according to modified Wessel's criteria, were randomly assigned to receive either L reuteri DSM 17 938 (10(8) colony-forming units) or placebo daily for 21 days. Parental questionnaires monitored daily crying time and adverse effects. Stool samples were collected for microbiologic analysis.
Forty-six infants (L reuteri group: 25; placebo group: 21) completed the trial. Daily crying times in minutes/day (median [interquartile range]) were 370 (120) vs 300 (150) (P=.127) on day 0 and 35.0 (85) vs 90.0 (148) (P=.022) on day 21, in the L reuteri and placebo groups, respectively. Responders (50% reduction in crying time from baseline) were significantly higher in the L reuteri group versus placebo group on days 7 (20 vs 8; P=.006), 14 (24 vs 13; P=.007), and 21 (24 vs 15; P=.036). During the study, there was a significant increase in fecal lactobacilli (P=.002) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only (P=.001). There were no differences in weight gain, stooling frequency, or incidence of constipation or regurgitation between groups, and no adverse events related to the supplementation were observed.
L. reuteri DSM 17 938 at a dose of 10(8) colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe. Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement.

Download full-text

Full-text

Available from: Roberto Calabrese, Aug 17, 2015
1 Follower
 · 
293 Views
  • Source
    • "Several clinical trials have shown diverse findings regarding DSM as an effective treatment to inhibit the symptoms of infantile colic (Savino et al., 2010; Szajewska et al., 2013; Sung et al., 2014). Since there is evidence that dichotomizing axons from T4-L1 DRG neurons innervate both the stomach and small intestine (Zhong et al., 2008) and because it is less invasive, we tested DSM's effects on the pseudoaffective responses to GDin vivo to supplement our ex vivo electrophysiological data (Results). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid (TRPV1) channel activity may mediate nociceptive signals we hypothesised that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin-evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglia neurons (DRG). Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin- and distension-evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin-evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited capsaicin-evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04). DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin-evoked excitability. The TRPV1 antagonist (6-iodonordihydrocapsaicin) or the use of TRPV1 knock-out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distention. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties.This article is protected by copyright. All rights reserved
    The Journal of Physiology 06/2015; DOI:10.1113/JP270229 · 4.54 Impact Factor
  • Source
    • "The microbiota of colicky infants also presents lower amounts of Bifidobacteria and Lactobacilli, which are known to be anti-inflammatory and to exert various healthy properties [19] [20] [21]. The intake of probiotic Lactobacilli during the first months of life can contribute to containing colic [22] [23]. On the contrary, in vivo studies utilizing probiotic Bifidobacteria for the treatment of colic are lacking. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Infant colic is a common gastrointestinal disorder of newborns, mostly related to imbalances in the composition of gut microbiota and particularly to the presence of gas-producing coliforms and to lower levels of Bifidobacteria and Lactobacilli. Probiotics could help to contain this disturbance, with formulations consisting of Lactobacillus strains being the most utilized. In this work, the probiotic strain Bifidobacterium breve B632 that was specifically selected for its ability to inhibit gas-producing coliforms, was challenged against the Enterobacteriaceae within continuous cultures of microbiota from a 2-month-old colicky infant. As confirmed by RAPD-PCR fingerprinting, B. breve B632 persisted in probiotic-supplemented microbiota cultures, accounting for the 64% of Bifidobacteria at the steady state. The probiotic succeeded in inhibiting coliforms, since FISH and qPCR revealed that the amount of Enterobacteriaceae after 18 h of cultivation was 0.42 and 0.44 magnitude orders lower in probiotic-supplemented microbiota cultures than in the control ones. These results support the possibility to move to another level of study, that is, the administration of B. breve B632 to a cohort of colicky newborns, in order to observe the behavior of this strain in vivo and to validate its effect in colic treatment.
    BioMed Research International 08/2014; 2014. DOI:10.1155/2014/301053 · 2.71 Impact Factor
  • Source
    • "Median daily crying time (min/d), by diary 1, 7, 14, 21, and 28 d (Primary) Savino et al, 31 2010 RCT, DB n = 46 "
    [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Excessive infant crying is common, distressing, but without proven effective prevention or management options. Probiotics may be a promising solution. OBJECTIVE To examine whether probiotics are effective in the prevention/management of crying ("colic") in infants 3 months or younger. DATA SOURCES A systematic search of MEDLINE, EMBASE, and the Cochrane Library, supplemented by the metaRegister of Controlled Trials. STUDY SELECTION Studies that randomized infants 3 months or younger to oral probiotics vs placebo or no or standard treatment with the outcome of infant crying, measured as the duration or number of episodes of infant crying/distress or diagnosis of "infant colic." Twelve of the 1180 initially identified studies were selected. DATA EXTRACTION AND SYNTHESIS This review/meta-analysis was conducted according to guidelines from the Cochrane Handbook for Systematic Reviews of Interventions, with reporting following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were independently extracted by 3 of us. MAIN OUTCOME(S) AND MEASURE(S) Infant crying, measured as the duration or number of episodes of infant crying/distress, or diagnosis of "infant colic." RESULTS Of the 12 trials (1825 infants) reviewed, 6 suggested probiotics reduced crying, and 6 did not. Three of the 5 management trials concluded probiotics effectively treat colic in breastfed babies; 1 suggested possible effectiveness in formula-fed babies with colic, and 1 suggested ineffectiveness in breastfed babies with colic. Meta-analysis of 3 small trials of breastfed infants with colic found that Lactobacillus reuteri markedly reduced crying time at 21 days (median difference, -65 minutes/d; 95% CI, -86 to -44). However, all trials had potential biases. Meanwhile, of 7 prevention trials, 2 suggested possible benefits. Considerable variability in the study populations, study type, delivery mode/dose of probiotic supplementation, and outcomes precluded meta-analysis. CONCLUSIONS AND RELEVANCE Although L reuteri may be effective as treatment for crying in exclusively breastfed infants with colic, there is still insufficient evidence to support probiotic use to manage colic, especially in formula-fed infants, or to prevent infant crying. Results from larger rigorously designed studies applicable to all crying infants will help draw more definitive conclusions.
    10/2013; 167(12). DOI:10.1001/jamapediatrics.2013.2572
Show more