Search

Background: Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo., Methods: This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed., Results: In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines., Conclusions: The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.

Recent metanalysis reported that certain probiotic strains, such as Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus (LGG), seem effective for treatment of infantile colic of exclusively breastfed infants; some reports have also linked probiotics to have an immunological effect, however further investigation are needed to fully understand the exact mechanism. The objective of this study was to assay white blood cells, tumour necrosis factor (TNF)-α and interleukin (IL)-6 values in peripheral blood in subjects treated in a randomised, double-blind, placebo-controlled trial for infantile colic with LGG. Fifty-eight infants were enrolled and followed for a study period of 28 days. Parent were asked to record daily crying time using a structured cry diary. Peripheral white blood cells was assessed and RNA (mRNA) expression of TNF-α and IL-6 was measured using TaqMan real-time PCR-maternal amplification. Infants with colic treated with LGG showed a reduction in daily crying duration after 28 days of treatment and a reduction in values of IL-6 ( P < 0.005) and TNF-α ( P < 0.05); we observe also a significantly decreasing of IL-6 in the placebo group while decrease of TNF-α was not significant in this group. A significant decreased values of monocytes ( P < 0.05) was observed in infants treated with LGG. Our data therefore showed, in addition to crying time reduction, a significant decrease of TNF-α and a significant reduction of monocytes cells in colicky infants treated with LGG, compared to placebo group. This observation supports the hypothesis that probiotics may have anti-inflammatory properties. Further studies are needed to better understand the influence of probiotic on immunity cells.

Background: The aim of this study was to investigate the efficacy of Lactobacillus rhamnosus ATCC 53103 together with the maternal diet avoidance of cow's milk in treating infantile colic., Methods: Forty-five colicky breastfed infants were consecutively randomized to receive L. rhamnosus for 28 days at a dosage of 5 × 10 9 cfu per day or placebo. Faecal samples were collected from each subject before starting supplementation and at the end of the study period and were immediately analysed. Faecal calprotectin was detected via a quantitative assay. The total bacterial load and selected bacterial species were evaluated using real-time TaqMan PCR., Results: After supplementation for 28 days with Lactobacillus rhamnosus ATCC 53103, median full-force daily crying was reduced (104 versus 242 min, p < 0.001) and the values of faecal calprotectin decreased significantly ( p = 0.026). Furthermore, the probiotic increased the abundance of Lactobacillus ( p = 0.048) and total bacteria ( p = 0.040); all these effects were not observed in the placebo group., Conclusion: Infants treated with Lactobacillus rhamnosus ATCC 53103 for 28 days, in association with the elimination of cow's milk from the maternal diet, presented some interesting features related to the effect of this probiotic treatment: reductions in crying time and faecal calprotectin, with increased total bacteria and Lactobacillus. To validate these results, a double-blind, placebo-controlled trial on a larger cohort is required., Competing Interests: The authors have no conflicts of interest to declare.

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 (1×10 8 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.

Background: Infantile colic is typically defined as full-force crying for at least three hours per day, on at least three days per week, for at least three weeks. This condition appears to be more frequent in the first six weeks of life (prevalence range of 17% to 25%), depending on the specific location reported and definitions used, and it usually resolves by three months of age. The aetiopathogenesis of infantile colic is unclear but most likely multifactorial. A number of psychological, behavioural and biological components (food hypersensitivity, allergy or both; gut microflora and dysmotility) are thought to contribute to its manifestation. The role of diet as a component in infantile colic remains controversial., Objectives: To assess the effects of dietary modifications for reducing colic in infants less than four months of age., Search Methods: In July 2018 we searched CENTRAL, MEDLINE, Embase , 17 other databases and 2 trials registers. We also searched Google, checked and handsearched references and contacted study authors., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of dietary modifications, alone or in combination, for colicky infants younger than four months of age versus another intervention or placebo. We used specific definitions for colic, age of onset and the methods for performing the intervention. We defined 'modified diet' as any diet altered to include or exclude certain components., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary outcome was duration of crying, and secondary outcomes were response to intervention, frequency of crying episodes, parental/family quality of life, infant sleep duration, parental satisfaction and adverse effects., Main Results: We included 15 RCTs involving 1121 infants (balanced numbers of boys and girls) aged 2 to 16 weeks. All studies were small and at high risk of bias across multiple design factors (e.g. selection, attrition). The studies covered a wide range of dietary interventions, and there was limited scope for meta-analysis. Using the GRADE approach, we assessed the quality of the evidence as very low.Low-allergen maternal diet versus a diet containing known potential allergens: one study (90 infants) found that 35/47 (74%) of infants responded to a low-allergen maternal diet, compared with 16/43 (37%) of infants on a diet containing known potential allergens.Low-allergen diet or soy milk formula versus dicyclomine hydrochloride: one study (120 infants) found that 10/15 (66.6%) breastfed babies responded to dicyclomine hydrochloride, compared with 24/45 (53.3%) formula-fed babies. There was little difference in response between breastfed babies whose mother changed their diet (10/16; 62.5%) and babies who received soy milk formula (29/44; 65.9%).Hydrolysed formula versus standard formula: two studies (64 infants) found no difference in duration of crying, reported as a dichotomous outcome: risk ratio 2.03, 95% confidence interval (CI) 0.81 to 5.10; very low-quality evidence. The author of one study confirmed there were no adverse effects. One study (43 infants) reported a greater reduction in crying time postintervention with hydrolysed formula (104 min/d, 95% CI 55 to 155) than with standard formula (3 min/d, 95% CI -63 to 67).Hydrolysed formula versus another hydrolysed formula: one study (22 infants) found that two types of hydrolysed formula were equally effective in resolving symptoms for babies who commenced with standard formula (Alimentum reduced crying to 2.21 h/d (standard deviation (SD) 0.40) and Nutramigen to 2.93 h/d (SD 0.70)).Hydrolysed formula or dairy- and soy-free maternal diet versus addition of parental education or counselling: one study (21 infants) found that crying time decreased to 2.03 h/d (SD 1.03) in the hydrolysed or dairy- and soy-free group compared with 1.08 h/d (SD 0.7) in the parent education or counselling group, nine days into the intervention.Partially hydrolysed, lower lactose, whey-based formulae containing oligosaccharide versus standard formula with simethicone: one study (267 infants) found that both groups experienced a decrease in colic episodes (secondary outcome) after seven days (partially hydrolysed formula: from 5.99 episodes (SD 1.84) to 2.47 episodes (SD 1.94); standard formula: from 5.41 episodes (SD 1.88) to 3.72 episodes (SD 1.98)). After two weeks the difference between the two groups was significant (partially hydrolysed: 1.76 episodes (SD 1.60); standard formula: 3.32 episodes (SD 2.06)). The study author confirmed there were no adverse effects.Lactase enzyme supplementation versus placebo: three studies (138 infants) assessed this comparison, but none reported data amenable to analysis for any outcome. There were no adverse effects in any of the studies.Extract of Foeniculum vulgare, Matricariae recutita, and Melissa officinalis versus placebo: one study (93 infants) found that average daily crying time was lower for infants given the extract (76.9 min/d (SD 23.5), than infants given placebo (169.9 min/d (SD 23.1), at the end of the one-week study. There were no adverse effects.Soy protein-based formula versus standard cows' milk protein-based formula: one study (19 infants) reported a mean crying time of 12.7 h/week (SD 16.4) in the soy formula group versus 17.3 h/week (SD 6.9) in the standard cows' milk group, and that 5/10 (50%) responded in the soy formula group versus 0/9 (0%) in the standard cows' milk group.Soy protein formula with polysaccharide versus standard soy protein formula: one study (27 infants) assessed this comparison but did not provide disaggregated data for the number of responders in each group after treatment.No study reported on our secondary outcomes of parental or family quality of life, infant sleep duration per 24 h, or parental satisfaction., Authors' Conclusions: Currently, evidence of the effectiveness of dietary modifications for the treatment of infantile colic is sparse and at significant risk of bias. The few available studies had small sample sizes, and most had serious limitations. There were insufficient studies, thus limiting the use of meta-analysis. Benefits reported for hydrolysed formulas were inconsistent.Based on available evidence, we are unable to recommend any intervention. Future studies of single interventions, using clinically significant outcome measures, and appropriate design and power are needed.

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 8  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., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: Lactobacillus reuteri DSM17938 has shown promise in managing colic, but conflicting study results have prevented a consensus on whether it is truly effective., Objective: Through an individual participant data meta-analysis, we sought to definitively determine if L reuteri DSM17938 effectively reduces crying and/or fussing time in infants with colic and whether effects vary by feeding type., Data Sources: We searched online databases (PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, the Database of Abstracts of Reviews of Effects, and Cochrane), e-abstracts, and clinical trial registries., Study Selection: These were double-blind randomized controlled trials (published by June 2017) of L reuteri DSM17398 versus a placebo, delivered orally to infants with colic, with outcomes of infant crying and/or fussing duration and treatment success at 21 days., Data Extraction: We collected individual participant raw data from included studies modeled simultaneously in multilevel generalized linear mixed-effects regression models., Results: Four double-blind trials involving 345 infants with colic (174 probiotic and 171 placebo) were included. The probiotic group averaged less crying and/or fussing time than the placebo group at all time points (day 21 adjusted mean difference in change from baseline [minutes] -25.4 [95% confidence interval (CI): -47.3 to -3.5]). The probiotic group was almost twice as likely as the placebo group to experience treatment success at all time points (day 21 adjusted incidence ratio 1.7 [95% CI: 1.4 to 2.2]). Intervention effects were dramatic in breastfed infants (number needed to treat for day 21 success 2.6 [95% CI: 2.0 to 3.6]) but were insignificant in formula-fed infants., Limitations: There were insufficient data to make conclusions for formula-fed infants with colic., Conclusions: L reuteri DSM17938 is effective and can be recommended for breastfed infants with colic. Its role in formula-fed infants with colic needs further research., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Sung reports personal fees from Mead Johnson Nutrition outside the submitted work; Dr Tancredi reports personal fees from Pfizer Consumer Healthcare outside the submitted work; Dr Cabana reports personal fees from BioGaia outside the submitted work; Dr Szajewska reports personal fees from BioGaia outside the submitted work; and Dr Dupont reports on the following outside the submitted work: Nutricia Research’s Scientific Advisory Board, Nestle Health Science Scientific Advisory Board, Sodilac Consulting, and Novalac clinical trials. Dr Savino reports the following outside the submitted work: received fees for scientific consultancy from Nestlé Italia (Assago, Milan), HiPP GmbH & Company Vertrieb KG (Germany), and Danone Trading BV (Amsterdam); he receives royalties from Springer for the book Nutrizione Parenterale in Pediatria and declares that the book does not cover any interventions investigated in the article and is outside the submitted work; he has received travel grants, accommodations, and meeting expenses from Cana Pharmaceutical Laboratories (Iraklio, Attica), Radiotelevisione Italiana (Rome), Nestlé Italy, and Nestlé France; he has received personal fees from Mead Johnson Nutrition Italy, Cana Laboratories (Thessaloniki, Greece), Nutricia (part of Groupe Danone; Dubai, United Arab Emirates, and Kuwait); HiPP GmbH & Company Vertrieb KG (Germany), and Menarini Farmaceutica Internazionale (Firenze); and he declares that none of these companies had any input or involvement in any aspect of the manuscript conducted by him or have a real or vested interest in the findings of the article. Dr Indrio reports, outside of the submitted work, being a consultant for BioGaia for an educational program for its Web site and being a speaker for the bureaus for the Nestle Nutrition Institute, Abbot Danone, and BioGaia at scientific events and lectures; and the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Aim: This study compared the faecal microbial composition of formula-fed infants who did and did not have colic., Methods: Faecal samples from formula-fed infants under 16 weeks of age with (n = 38) and without (n = 39) colic were collected at Department of Pediatrics in Turin, Italy, between February 2014 and October 2015. The pH and faecal ammonia were determined and total bacteria, bifidobacteria, lactic acid bacteria and coliforms were quantified by fluorescent in situ hybridisation (FISH)., Results: Faecal ammonia was significantly higher in the colicky infants than in the controls (483 vs. 216 μg/g, p < 0.05). The FISH counts of total bacteria were lower in colicky infants (1.8E10 ± 1.5E10) than in the controls (3.4E10 ± 3.0E10) (p < 0.05). The relative abundance of coliform bacteria was significantly higher in colicky infants (p < 0.05). No differences were observed for the bifidobacteria and lactic acid bacteria counts between the two groups., Conclusion: Our comparison of formula-fed infants with and without colic revealed significant differences in total bacteria, Enterobacteriaceae and faecal ammonia. This study provides the stimulus for further studies of the gut microbiome, using new methods of analysis such as 16S metagenomics sequencing in order to lead to more tailored dietary approaches., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Infants were recruited in four centres in North-West Italy. 138 infants were assessed for eligibility, 113 ones underwent randomisation and 105 completed the study. Newborns aged less than 10 days of life, with gestational age between 37 and 42 weeks, birth weight from 2,500 to 4,300 g and normal physical examination were recruitable. Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded. Patients were randomly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 (108 cfu) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily. The primary endpoints concern the administration of pain relieving agents (cimetropium bromide at least three times per week or simethicone at least five times per week) from baseline to 12 weeks. Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks. Data concerning the number of calls to the paediatricians and the number of visits at paediatricians' ambulatories due to infantile colic have been collected by paediatrician and analysed. Comparing the two groups, the relative risk was 0.04 (95% confidence interval (CI)=0.01-0.31) for cimetropium bromide, 0.24 (95% CI=0.14-0.41) for simethicone and 0.37 (95% CI=0.17-0.80) for the administration of infant formula, showing a protective action of L. reuteri. The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group (P<0.0001). L. reuteri DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic. The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic, as well as use of pain relieving agents and of infant formula.

Introduction: Infant colic, or excessive crying of unknown cause in infants less than 3 months old, is common and burdensome. Its aetiology is undetermined, and consensus on its management is still lacking. Recent studies suggest a possible link between infant colic and gut microbiota, indicating probiotics to be a promising treatment. However, only a few strains have been tested, and results from randomised controlled trials are conflicting. It is important to clarify whether probiotics are effective for treating infant colic in general, and to identify whether certain subgroups of infants with colic would benefit from particular strains of probiotics., Methods and Analysis: Through an individual participant data meta-analysis (IPDMA), we aim to identify whether the probiotic Lactobacillus reuteri DSM 17938 is effective in the management of infant colic, and to clarify whether its effects differ according to feeding method (breast vs formula vs combined), proton pump inhibitor exposure, and antibiotic exposure. The primary outcomes are infant crying duration and treatment success (at least 50% reduction in crying time from baseline) at 21 days postintervention. Individual participant data from all studies will be modelled simultaneously in multilevel generalised linear mixed-effects regression models to account for the nesting of participants within studies. Subgroup analyses of participant-level and intervention-level characteristics will be undertaken on the primary outcomes to assess if the intervention effect differs between certain groups of infants., Ethics and Dissemination: Approved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015., Trial Registration Number: PROSPERO CRD42014013210., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Infantile colic is a common disturbance occurring in the first three months of life. It is a benign condition and one of the main causes of pediatric consultation in the early part of life because of its great impact on family life. Some pediatricians are prone to undervalue this issue mainly because of the lack of evidence based medicine guidelines. Up to now, there is no consensus concerning management and treatment. Literature reports growing evidence about the effectiveness of dietary, pharmacological, complementary and behavioral therapies as options for the management of infantile colic. Dietary approach, usually based on the avoidance of cow's milk proteins in breast-feeding mothers and bottle-fed infants, more recently has seen the rise of new special formulas, such as partially hydrolyzed proteins and low lactose added with prebiotics or probiotics: their efficacy needs to be further documented. Investigated pharmacological agents are Simethicone and Cimetropium Bromide: the first is able to reduce bloating while the second could reduce fussing crying, but it has been tested only for severe infantile colic. No other pain relieving agents have been proposed until now, but some clinical trials are ongoing for new drugs.There is limited evidence supporting the use of complementary and alternative treatments (herbal supplements, manipulative approach and acupuncture) or behavioral interventions.Recent studies have focused the role of microbiota in the pathogenesis of this disturb and so new treatments, such as probiotics, have been proposed, but only few strains have been tested.Further investigations are needed in order to provide evidence-based guidelines.

Objective: To analyze the global microbial composition, using large-scale DNA sequencing of 16 S rRNA genes, in faecal samples from colicky infants given L. reuteri DSM 17938 or placebo., Methods: Twenty-nine colicky infants (age 10-60 days) were enrolled and randomly assigned to receive either Lactobacillus reuteri (10(8) cfu) or a placebo once daily for 21 days. Responders were defined as subjects with a decrease of 50% in daily crying time at day 21 compared with the starting point. The microbiota of faecal samples from day 1 and 21 were analyzed using 454 pyrosequencing. The primers: Bakt&#95;341F and Bakt&#95;805R, complemented with 454 adapters and sample specific barcodes were used for PCR amplification of the 16 S rRNA genes. The structure of the data was explored by using permutational multivariate analysis of variance and effects of different variables were visualized with ordination analysis., Results: The infants' faecal microbiota were composed of Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes as the four main phyla. The composition of the microbiota in infants with colic had very high inter-individual variability with Firmicutes/Bacteroidetes ratios varying from 4000 to 0.025. On an individual basis, the microbiota was, however, relatively stable over time. Treatment with L. reuteri DSM 17938 did not change the global composition of the microbiota, but when comparing responders with non-responders the group responders had an increased relative abundance of the phyla Bacteroidetes and genus Bacteroides at day 21 compared with day 0. Furthermore, the phyla composition of the infants at day 21 could be divided into three enterotype groups, dominated by Firmicutes, Bacteroidetes, and Actinobacteria, respectively., Conclusion: L. reuteri DSM 17938 did not affect the global composition of the microbiota. However, the increase of Bacteroidetes in the responder infants indicated that a decrease in colicky symptoms was linked to changes of the microbiota., Trial Registration: ClinicalTrials.gov NCT00893711.

Background: Infantile colic is a common disturb within the first 3 months of life, nevertheless the pathogenesis is incompletely understood and treatment remains an open issue. Intestinal gas production is thought to be one of the causes of abdominal discomfort in infants suffering from colic. However, data about the role of the amount of gas produced by infants' colonic microbiota and the correlation with the onset of colic symptoms are scanty. The benefit of supplementation with lactobacilli been recently reported but the mechanisms by which they exert their effects have not yet been fully defined. This study was performed to evaluate the interaction between Lactobacillus spp. strains and gas-forming coliforms isolated from stools of colicky infants., Results: Strains of coliforms were isolated from stools of 45 colicky and 42 control breastfed infants in McConkey Agar and identified using PCR with species-specific primers, and the BBL™ Enterotube™ II system for Enterobacteriaceae. Gas-forming capability of coliforms was assessed in liquid cultures containing lactose as sole carbon source. The average count of total coliforms in colicky infants was significantly higher than controls: 5.98 (2.00-8.76) log10 vs 3.90 (2.50-7.10) CFU/g of faeces (p = 0.015). The following strains were identified: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae and Enterococcus faecalis. Then, 27 Lactobacillus strains were tested for their antagonistic effect against coliforms both by halo-forming method and in liquid co-cultures. Lactobacillus delbrueckii subsp. delbrueckii DSM 20074 and L. plantarum MB 456 were able to inhibit all coliforms strains (halo-forming method), also in liquid co-cultures, thus demonstrating an antagonistic activity., Conclusions: This study shows that two out of 27 strains of Lactobacillus examined possess an antimicrobial effect against six species of gas-forming coliforms isolated from colicky infants. Our findings may stimulate new researches to identify which Lactobacillus strains can improve colicky symptoms by acting on coliforms gut colonization.

Purpose of Review: Infantile colic is a common problem within the first 3 months of life and causes considerable distress for parents and paediatricians. Despite 40 years of research, its pathogenesis is incompletely understood and treatment remains an open issue. This review will describe recent studies that have examined different kinds of interventions., Recent Findings: Important advances in understanding the aetiopathogenesis of infantile colic have been recently proposed and opened new perspectives in its management.The composition of intestinal microbiota, specially an inadequate amount of lactobacilli and an increased concentration of coliforms, might influence the pathogenesis of infantile colic. The benefit of supplementation with Lactobacillus reuteri has been recently reported and experimental data showed the effect of probiotics may be related to the influence on gut motility and pain perception., Summary: Infantile colic is a clinical entity with a wide range of clinical presentations and outcome. Firstly, paediatricians have to exclude other underlying diseases with a medical examination and prevent feeding disorders. Then, considering the favourable clinical course of the disturbance, well tolerated strategies should be adopted. The findings highlighted in this review may promote the implementation of new researches and treatments to reduce abdominal pain related to infantile colic.

Objective: To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota., Study Design: 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., Results: 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., Conclusion: 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.

Objective: To determine the presence of intestinal coliform bacteria in colicky vs healthy infants., Study Design: We isolated coliform strains from faeces and performed quantitative bacterial cultures in 41 colicky and 39 healthy breastfed infants, identified using PCR with species-specific primers, strain-specific Automated Ribotyping and the API-50E kit for Enterobacteriaceae to identify the most frequent strains., Results: Coliform strains were more abundant in colicky infants (median 6.04 log(10) CFU/g faeces, range 2.00-8.76) vs controls (median 4.47 log(10) CFU/g faeces, range 1.00-8.08) (p = 0.026). Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Enterobacter cloacae, E. aerogenes and Enterococcus faecalis were the predominant species in colicky and healthy infants. The counts of each bacterial species differed between the two groups, and the difference was significant (p = 0.002) for E. coli: median 6.30 log(10) CFU/g faeces (range 3.00-8.74) in colicky infants, and median 4.70 log(10) CFU/g faeces (range 2.00-5.85) in controls., Conclusions: This is the first study to evaluate the colonization patterns of gas-forming coliforms in colicky infants and healthy controls identified by molecular methods. Coliform bacteria, particularly Escherichia coli, were found to be more abundant in colicky infants. Our data could help to shed light on the cause of infantile colic.

Unlabelled: Infantile colic is a widespread clinical condition in the first 3 months of life, which is easily recognized, but incompletely understood and difficult to solve. The available evidence suggests that infantile colic might have several independent causes. The medical hypotheses include food hypersensitivity or allergy, immaturity of gut function and dysmotility, and the behavioural hypotheses include inadequate maternal-infant interaction, anxiety in the mother and difficult infant temperament. Other recent hypotheses, such as hormone alterations and maternal smoking, still need confirmation, whereas the new concept of alterations in the gut microflora, have been reported. A number of interventions, including pharmacological agents, are discussed, but it is probable that infants with colic require a graded strategy., Conclusion: Considering the favourable clinical course and the wide range of manifestations, a safe approach should be adopted, which is proportional to the intensity of the infantile colic. However, further research and guidelines are still needed.

Objective: The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospective randomized study would improve symptoms of infantile colic., Methods: Ninety breastfed colicky infants were assigned randomly to receive either the probiotic L. reuteri (10(8) live bacteria per day) or simethicone (60 mg/day) each day for 28 days. The mothers avoided cow's milk in their diet. Parents monitored daily crying times and adverse effects by using a questionnaire., Results: Eighty-three infants completed the trial: 41 in the probiotic group and 42 in the simethicone group. The infants were similar regarding gestational age, birth weight, gender, and crying time at baseline. Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day, respectively, on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day. On day 28, 39 patients (95%) were responders in the probiotic group and 3 patients (7%) were responders in the simethicone group. No adverse effects were reported., Conclusions: In our cohort, L. reuteri improved colicky symptoms in breastfed infants within 1 week of treatment, compared with simethicone, which suggests that probiotics may have a role in the treatment of infantile colic.

Objectives: The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins, prebiotic oligosaccharides (OS), with a high beta-palmitic acid content., Design: Prospective randomized controlled study., Setting: Italy., Subjects: Two hundred and sixty-seven formula-fed infants, aged less than 4 months, with infantile colic, were randomized to receive either the new infant formula (study treatment (ST)) or a standard formula and simethicone (6 mg/kg twice a day) (control treatment (CT)). A questionnaire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time., Results: Out of the 199 infants who completed the study, 96 were treated with the new formula and 103 were not treated. Infants receiving the new formula had a significant decrease in colic episodes after 1 week (2.47+/-1.94 at day 7 vs 5.99+/-1.84 at the study entry) compared to infants receiving the CT (3.72+/-1.98 at day 7 vs 5.41+/-1.88 at the study entry) (P < 0.0001). Also at day 14, the crying episodes were significantly different between the two groups of infants (1.76+/-1.60 in ST vs 3.32+/-2.06 in CT) (P < 0.0001)., Conclusions: The use of a partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a standard formula and simethicone.

Aim: To evaluate serum ghrelin and motilin concentration in infants with infantile colic., Methods: A case-control study was conducted on fasting blood venous samples obtained from 18 infants with infantile colic and 20 healthy infants to measure ghrelin (RIA test) and motilin (RIA test)., Results: Colicky infants showed higher ghrelin serum levels (2534.2 +/- 600.0 pg/ml; ln 7.8 +/- 0.2) than controls (2126.1 +/- 281.3 pg/ml; ln 7.6 +/- 0.1) (p = 0.011). Serum motilin concentration was significantly higher in colicky infants (94.6 +/- 23.2 pmol/l) than in controls (64.1 +/- 30.1 pmol/l) (p = 0.001). Motilin concentrations were higher in formula-fed colicky infants (104.5 +/- 20.4 pmol/l) than in breastfed ones (82.2 +/- 21.3 pmol/l) (p = 0.038)., Conclusion: Our finding shows that ghrelin and motilin concentrations are higher in infants with colic than in controls, supporting an organicistic aetiopathogenesis of this disorder. Furthermore, the role of ghrelin on gastrointestinal motility may open new doors to better understand the aetiology of infantile colic.

Aim: To evaluate the association between infantile colic and gastrointestinal, allergic and psychological disorders in childhood., Methods: A prospective study was conducted on 103 infants aged 31-87 d. After 10 y, between 2001 and 2003, the children were recalled and a paediatrician evaluated the selected disorders by anamnesis, medical examination, laboratory tests and parent interviews., Results: Of the 103 infants enrolled, 96 completed the study. There was an association between infantile colic and recurrent abdominal pain (p=0.001) and allergic disorders: allergic rhinitis, conjunctivitis, asthmatic bronchitis, pollenosis, atopic eczema and food allergy (p<0.05). Sleep disorders, fussiness, aggressiveness and feelings of supremacy are more frequent in children who suffered from colic during early infancy (p<0.05). A family history of gastrointestinal diseases and atopic diseases was significantly higher in infants with colic than in controls (p<0.05)., Conclusion: Susceptibility to recurrent abdominal pain, allergic and psychological disorders in childhood may be increased by infantile colic. Our findings confirm that severe infantile colic might be the early expression of some of the most common disorders in childhood.

Objective: The aim of this randomized, double-blind, placebo-controlled trial was to investigate the effectiveness and side effects of a phytotherapeutic agent with Matricariae recutita, Foeniculum vulgare and Melissa officinalis in the treatment of infantile colic., Methods: 93 breastfed colicky infants were enrolled, the diagnosis was made according to Wessel's criteria. After a 3 day observation period, the infants were randomly divided into two groups, one treated with phytotherapeutic agent (PA) and the other with placebo twice a day for 1 week. Crying time and side effects were recorded., Results: 88 infants completed the trial: 41 in the PA group and 47 in the control. The daily average crying time for the PA was 201.2 min/day (SD 18.3) at the baseline and 76.9 min/day (SD 23.5) at the end of the study; for the placebo it was 198.7 min/day (SD 16.9) and 169.9 min/day (SD 23.1) (p < 0.005). Crying time reduction was observed in 85.4% subjects for the PA and in 48.9% subjects for the placebo (p < 0.005). No side effects were reported., Conclusion: The present study shows that colic in breastfed infant improves within 1 week of treatment with an extract based on Matricariae recutita, Foeniculum vulgare and Melissa officinalis., ((c) 2005 John Wiley & Sons, Ltd.)

Intestinal colonization by lactobacilli is suggested to be a prerequisite to normal mucosal immune functions. An inadequate level of lactobacilli may be involved in appearance of allergic disease of which, infantile colic, is often considered an early clinical manifestation. The aim of the study is to evaluate intestinal lactobacilli in breast-fed infants with infantile colic and healthy infants. Fifty-six breast-fed infants, aged 15-60 days were enrolled in the study and divided into two groups: colicky (30 cases) and healthy (26 cases) according to Wessel's criteria. Stool samples were collected, diluted and cultured on selective media. The colonies were counted, reported as colony forming unit (cfu) per gram of faeces and identified by biochemical methods. Different colonization patterns of lactobacilli were found among colicky and healthy infants. Lactobacillus brevis (4.34 x 10(8) cfu/g) and L. lactis lactis (2.51 x 10(7) cfu/g) were found only in colicky infants while L. acidophilus (2.41 x 10(7) cfu/g) was found only in healthy infants. Lactobacillus brevis and L. lactis lactis might be involved in the pathogenesis of infantile colic increasing meteorism and abdominal distension. Further studies are required to understand how the observed differences may be involved in the pathogenesis of this common disorder.

Background: Infantile colics are a common problem in the first months of life. During this period, a process of intestinal colonization rapidly occurs. A difference in the gut microflora could play an important role in the pathogenesis of colics, changing the metabolism of carbohydrates and fatty acids. Actually, in the literature, only few data have been collected about this topic. In this study, we evaluated intestinal microflora in breastfed colicky and non-colicky infants., Methods: Seventy-one breastfed infants, aged 3.2 +/- 0.6 wk, free from episodes of gastroenteritis and without previous assumption of antibiotic and probiotic drugs, were enrolled in the study. They were divided into two groups: colicky (42 cases) and non-colicky (29 cases), according to Wessel's criteria. Stool samples were collected, diluted and cultured on several selective media to detect lactobacilli, clostridia, gram-negative anaerobes and Enterobacteriaceae. Statistical analysis was performed using Student's t-test, chi2 test and a non-parametric test (Mann-Whitney U-test)., Results: Differences in gut microflora were found among colicky and non-colicky infants: colicky infants were less frequently colonized by Lactobacillus spp., and more frequently by anaerobic gram-negative bacteria., Conclusion: Our study indicates that colicky infants have different patterns of gut microflora. Further studies are required to understand whether gut microflora is the primary cause of colics or its consequence.

Background: Colic, regurgitation and constipation are common feeding problems in formula-fed infants that might benefit from dietary treatment. A formula containing fructo- and galacto-oligosaccharides, partially hydrolysed proteins, low levels of lactose and palmitic acid in the beta position and higher density has been tested to reduce the occurrence of these symptoms. The aim of this prospective study was to describe the effects of such a formula in infants with minor gastrointestinal disorders., Methods: An observational prospective trial involving practising Italian paediatricians was performed. Formula fed-infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and/or regurgitation and/or constipation were enrolled in the study from January 2001 to May 2001. The study was completed within 14 d of treatment. On days 1, 7 and 14 the infants were visited by the paediatricians. Parents were given a structured diary to record daily episodes of colic, regurgitation and type and number of stools., Results: Of the 932 infants enrolled, 604 completed the study. Of the 214 infants with colic, 169 (79%) demonstrated a reduction in frequency of colic from 4.1 +/- 2.0 per day at the beginning of the study to 2.0 +/- 1.8 at the end of the study (I.C. 95%: 1.72-2.39; p < 0.005). A reduction in the number of episodes of colic of 1.8 per day at the beginning of the study (I.C. 95%: 1.49-2.11; p < 0.05) was recorded between day 1 and day 7, and of 0.26 (I.C. 95%: 0.15-0.37; p < 0.05) between day 7 and day 14. Of the 201 infants with regurgitation problems, 141 (70%) demonstrated a reduction of frequency of the symptoms from 4.2 +/- 2.0 per day at the beginningof the study to 2.1 +/- 2.2 at the end of the study (I.C. 95%: 1.75-2.35; p < 0.005). A reduction of 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 (I.C. 95%: 1.57-2.16; p < 0.05) and of 0.18 (I.C. 95%: 0.06-0.31; p < 0.05) between day 7 and day 14. Of the 232 infants with constipation, 147 (63%) demonstrated an increase in the daily number of stools of 0.42 (I.C. 95%: 0.5-0.3; p < 0.005). An increase in stool frequency of 0.41 (I.C. 95%: 0.51-0.23; p < 0.05) was reported between day 1 and day 7, and of 0.04 (I.C. 95%: 0.22-0.14; p = ns) between day 7 and day 14. Parents' evaluation of the formula was 7.9 +/- 1.8 (score 0-10); 550 parents (91%) gave a positive judgement (score > 6). The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 +/- 1.5; 574 (95%) a positive effect (score > 6)., Conclusion: This study shows that the majority of infants followed by paediatricians for minor gastrointestinal symptoms improve within 2 wk of feeding with this new formula. Further double-blind, controlled studies are needed to confirm whether the amelioration of symptoms observed in this trial is in fact due to the new formula.

Background: Treatment of infantile colic remains an open issue. In Italy, cimetropium bromide is used extensively to treat infantile colic. The aim of this randomized, double-blind, placebo-controlled clinical trial was to investigate the effectiveness and side effects of cimetropium bromide in the treatment of infants with colic crisis., Methods: Ninety-seven infants with colic were enrolled. The diagnosis of infantile colic in healthy infants with regular growth, aged 15 to 60 days was made according to the criteria of Wessel. The infants were divided into two groups, one treated with cimetropium bromide (1.2 mg/kg) and the other treated with placebo at onset of each crisis for 3 days. Duration of crying and side effects were recorded daily in a structured diary for the 3 days of therapy. Statistical analysis was performed using the chi-square and t tests., Results: Eighty-six infants completed the trial. The average duration of crying for each crisis was 17.3 +/- 12.6 minutes in the cimetropium bromide group and 47.5 +/- 28.5 minutes in the placebo group (P < 0.005). Response to cimetropium bromide was 74%. Response to placebo was 33% (P < 0.05). Side effects did not differ significantly between the two groups, except sleepiness, which increased in the infants treated with cimetropium bromide., Conclusion: Cimetropium bromide was more effective than placebo in reducing the duration of crying in children with infantile colic. The use of the anticholinergic drugs, aside from the dicyclomine because of its dangerous side effects, should be revaluated for treating infantile colic.

Unlabelled: Infantile colic concerns about 10-30% of all newborns and has been defined as a condition characterized by paroxysmal episodes of unexplained full force crying for at least three days a week and continuing for one week or more in a thriving well-nourished infant. The disorder more likely occurs in the evening, without identifiable causes and resolves spontaneously by the fourth month of life. The several factors involved in the etiopathogenesis (food intolerance or allergy to cow's milk protein, intolerance to lactose, intestinal hyperperistalsis, neuro-hormonal immaturity, maternal anxiety and familial stress), make the management of infants with colics difficult. We propose a scoring system for the evaluation of colics in infants based on: 1) crying intensity and duration; 2) accompanying characteristics of crises (e.g. meteorism, family history for allergic disease, type of feeding, type of stools); 3) evaluation of parents' opinion of their infants' crying. Type of management is based on the score: a) crying that is unrelated to colics: treatments referred to specific diagnosis. b) crying that is related to colics but not severe: first and second step of management; c) crying that is related to colics and is severe: third step of management., Management: first step: pacifier, rocking, dull continuous background noise, hot water bottle on the abdomen, herbal tea, simethicone. Second step: pharmacological treatment and periodic controls. Pharmacological treatment include antispastic drugs (e.g. cimetropium bromide). Third step: dietary modification and/or pharmacological treatment: mothers of breast-fed infants are given a diet with no milk or products containing its proteins, or fish, or eggs. Infants who are not breast-fed receive soy milk and if symptoms continue soy milk is substituted with hydrolyzed casein milk formula. Pharmacological treatment include antispastic drugs (e.g. cimetropium bromide and in non responders dicyclomine hydrochloride). Dietary modifications appear more suitable than pharmacological treatment in resolving symptoms, since side effects of drugs have been described and our recent results indicate appropriate dietary modifications offer better results than pharmacological treatment in resolving crises. However, before interrupting dietary modifications and reintroducing cow's milk proteins, infant's tolerance to such proteins is tested. In any case because of the good prognosis and rapid regression of symptoms, dietary regimens or pharmacological treatment should only be applied if really necessary and for brief periods under medical supervision.

This study examined 120 infants, aged 3-12 weeks, with severe colics and compared the results of a specific hypoallergenic diet (group A) with those of pharmacological treatment (group B). Non-breast-fed group A infants received soy milk and if unresponsive, hydrolyzed milk formulas; mothers of breast-fed infants received a diet without cow's milk, eggs or fish. Breast-fed and non-breast-fed group B infants received dicyclomine hydrochloride 3 mg/kg/day. Results, based on quantitative measurements of crying, indicated that in breast-fed infants there was no significant improvement between group A (62.5%) and group B (66.6%) infants. Among formula-fed infants, comparison of positive results using soy milk (65.9%) with positive results using dicyclomine (53.3%) was not significant; positive results using soy milk and hydrolyzed milk formulas in non-responders to soy milk, provided an improvement in 95.4% of cases. Pharmacological treatment provided an improvement in 53.3% of cases. The difference was significant (p < 0.01).

Savino F, Bailo E, Oggero R, Tullio V, Roana J, Carlone N, Cuffini AM, Silvestro L. Bacterial counts of intestinalLactobacillusspecies in infants with colic.Pediatr Allergy Immunol 2005: 16: 72–75.© 2005 Blackwell MunksgaardIntestinal colonization by lactobacilli is suggested to be a prerequisite to normal mucosal immune functions. An inadequate level of lactobacilli may be involved in appearance of allergic disease of which, infantile colic, is often considered an early clinical manifestation. The aim of the study is to evaluate intestinal lactobacilli in breast-fed infants with infantile colic and healthy infants. Fifty-six breast-fed infants, aged 15–60 days were enrolled in the study and divided into two groups: colicky (30 cases) and healthy (26 cases) according to Wessel's criteria. Stool samples were collected, diluted and cultured on selective media. The colonies were counted, reported as colony forming unit (cfu) per gram of faeces and identified by biochemical methods. Different colonization patterns of lactobacilli were found among colicky and healthy infants.Lactobacillus brevis(4.34 × 108 cfu/g) andL. lactis lactis(2.51 × 107 cfu/g) were found only in colicky infants whileL. acidophilus(2.41 × 107 cfu/g) was found only in healthy infants.Lactobacillus brevisandL. lactis lactismight be involved in the pathogenesis of infantile colic increasing meteorism and abdominal distension. Further studies are required to understand how the observed differences may be involved in the pathogenesis of this common disorder. [ABSTRACT FROM AUTHOR]