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Special Issue "Probiotics and Prebiotics in Pediatrics"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (30 September 2018)

Special Issue Editors

Guest Editor
Dr. Francesco Savino

Department of Pediatrics, Ospedale Infantile Regina Margherita, Azienda Ospedaliera, Universitaria Città della Salute e della Scienza di Torino, Piazza Polonia, 94, 10126 Turin, Italy
Website | E-Mail
Phone: +0039 0113135618
Fax: +0039 0113135010
Interests: infant nutrition; breastmilk; infant formulas; leptin; ghrelin; infantile colic; gut microbiota; prebiotics; probiotics
Guest Editor
Prof. Dr. Yvan Vandenplas

KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
Website | E-Mail
Phone: +02-477-5781

Special Issue Information

Dear Colleagues,

The goal of this Special Issue, “Probiotics and Prebiotics in Pediatrics”, is to focus on the importance of pediatric nutrition with probiotics and prebiotics to improve gastrointestinal health in newborn, infants, and children.

Specifically, the aim is to clarify if probiotics and prebiotics can influence gut microbiota composition and host-interaction favoring human health and preventing diseases.

This new information will provide health care professionals with a widespread, clear and update evidence on probiotics and prebiotics and intestinal gut microbiota in pediatric care.

Dr. Francesco Savino
Prof. Dr. Yvan Vandenplas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prebiotics
  • fructo-oligosaccharides
  • galacto-oligosaccharides
  • lactoferin
  • probiotics
  • gut microbiota
  • E. Coli
  • Lactobacilli
  • infant nutrition

Published Papers (18 papers)

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Editorial

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Open AccessEditorial Probiotics and Prebiotics in Pediatrics: What Is New?
Nutrients 2019, 11(2), 431; https://doi.org/10.3390/nu11020431
Received: 11 February 2019 / Accepted: 15 February 2019 / Published: 19 February 2019
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Abstract
Probiotics and prebiotics are a hot topic in pediatric research [...] Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)

Research

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Open AccessArticle Role of Lactobacillus rhamnosus (FloraActive™) 19070-2 and Lactobacillus reuteri (FloraActive™) 12246 in Infant Colic: A Randomized Dietary Study
Nutrients 2018, 10(12), 1975; https://doi.org/10.3390/nu10121975
Received: 30 October 2018 / Revised: 2 December 2018 / Accepted: 10 December 2018 / Published: 13 December 2018
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Abstract
Infant colic is a common condition of unknown pathogenesis that brings frustration to families seeking for effective management. Accumulating evidence suggests that some single strains of lactobacilli may play a positive dietary role in attenuation of colic in exclusively breastfed infants. The objective [...] Read more.
Infant colic is a common condition of unknown pathogenesis that brings frustration to families seeking for effective management. Accumulating evidence suggests that some single strains of lactobacilli may play a positive dietary role in attenuation of colic in exclusively breastfed infants. The objective of this study was to evaluate a mixture of two Lactobacillus strains in decreasing infant cry and fuss in this population. Infants aged 4–12 weeks received L. rhamnosus 19070-2 and L. reuteri 12246 in a daily dose of 250 × 106 CFU, 3.33 mg of fructooligosaccharide, and 200 IU of vitamin D3 (84 infants, probiotic group) or just vitamin D3 (84 infants, control group) for 28 days. Cry and fuss time were measured with validated Baby’s Day Diary on days 0 and 28. At baseline, mean (SD) duration of cry and fuss time was comparable in the probiotic and control groups: 305 (81) vs. 315 (90) min., respectively (p = 0.450). On day 28, mean cry and fuss time became statistically different: 142 (89) vs. 199 (72), respectively (p < 0.05). Mean change in cry and fuss time from day 0 through day 28 was −163 (99) minutes in the probiotic and −116 (94) minutes in the control group (p = 0.019). Our findings confirm that lactobacilli decrease cry and fuss time and provide a dietary support in exclusively breastfed infants with colic. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle A Randomized, Placebo-Controlled, Pilot Clinical Trial to Evaluate the Effect of Supplementation with Prebiotic Synergy 1 on Iron Homeostasis in Children and Adolescents with Celiac Disease Treated with a Gluten-Free Diet
Nutrients 2018, 10(11), 1818; https://doi.org/10.3390/nu10111818
Received: 16 October 2018 / Revised: 31 October 2018 / Accepted: 16 November 2018 / Published: 21 November 2018
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Abstract
Iron deficiency anemia (IDA) occurs in 15–46% of patients with celiac disease (CD), and in some cases, it may be its only manifestation. Studies in animal models have shown that prebiotics, including inulin, may help to increase intestinal absorption of iron. The aim [...] Read more.
Iron deficiency anemia (IDA) occurs in 15–46% of patients with celiac disease (CD), and in some cases, it may be its only manifestation. Studies in animal models have shown that prebiotics, including inulin, may help to increase intestinal absorption of iron. The aim of this study was to evaluate the effect of a prebiotic, oligofructose-enriched inulin (Synergy 1), on iron homeostasis in non-anemic children and adolescents with celiac disease (CD) in association with a gluten-free diet (GFD). Thirty-four CD patients (4–18 years old) were randomized into two groups receiving Synergy 1 (10 g/day) or a placebo (maltodextrin) for three months. Before and after intervention, blood samples were collected from all patients for assessment of blood morphology, biochemical parameters and serum hepcidin concentration. We found that serum hepcidin concentration after the intervention was significantly decreased by 60.9% (p = 0.046) in the Synergy 1 group, whereas no significant difference was observed in the placebo group. No differences in morphological and biochemical blood parameters (including ferritin, hemoglobin and C-reactive protein (CRP)) were observed after intervention in either group. Given that hepcidin decrease may improve intestinal iron absorption, these results warrant further investigation in a larger cohort and especially in patients with IDA. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle Efficacy of Lactobacillus Administration in School-Age Children with Asthma: A Randomized, Placebo-Controlled Trial
Nutrients 2018, 10(11), 1678; https://doi.org/10.3390/nu10111678
Received: 29 September 2018 / Revised: 26 October 2018 / Accepted: 29 October 2018 / Published: 5 November 2018
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Abstract
Probiotics may have immunomodulatory effects. However, these effects in asthma remain unclear and warrant clinical trials. Here, we evaluated the effects of Lactobacillus paracasei (LP), Lactobacillus fermentum (LF), and their combination (LP + LF) on the clinical severity, immune biomarkers, and quality of [...] Read more.
Probiotics may have immunomodulatory effects. However, these effects in asthma remain unclear and warrant clinical trials. Here, we evaluated the effects of Lactobacillus paracasei (LP), Lactobacillus fermentum (LF), and their combination (LP + LF) on the clinical severity, immune biomarkers, and quality of life in children with asthma. This double-blind, prospective, randomized, placebo-controlled trial included 160 children with asthma aged 6–18 years (trial number: NCT01635738), randomized to receive LP, LF, LP + LF, or a placebo for 3 months. Their Global Initiative for Asthma–based asthma severity, Childhood Asthma Control Test (C-ACT) scores, Pediatric Asthma Severity Scores, Pediatric Asthma Quality of Life Questionnaire scores, peak expiratory flow rates (PEFRs), medication use, the levels of immune biomarkers (immunoglobulin E (IgE), interferon γ, interleukin 4, and tumor necrosis factor α) at different visits, and the associated changes were evaluated. Compared with the placebo group by generalized estimating equation model, children receiving LP, LF, and LP + LF had lower asthma severity (p = 0.024, 0.038, and 0.007, respectively) but higher C-ACT scores (p = 0.005, < 0.001, and < 0.001, respectively). The LP + LF group demonstrated increased PEFR (p < 0.01) and decreased IgE levels (p < 0.05). LP, LF, or their combination (LP + LF) can aid clinical improvement in children with asthma. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle Randomized, Double-Blind, Placebo-Controlled Parallel Clinical Trial Assessing the Effect of Fructooligosaccharides in Infants with Constipation
Nutrients 2018, 10(11), 1602; https://doi.org/10.3390/nu10111602
Received: 8 September 2018 / Revised: 25 October 2018 / Accepted: 26 October 2018 / Published: 1 November 2018
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Abstract
Constipation often begins in the first year of life. The aim of this study was to assess the effect of fructooligosaccharides (FOS) in the treatment of infants with constipation. This randomized, double-blind, placebo-controlled clinical trial included infants with constipation who were randomly assigned [...] Read more.
Constipation often begins in the first year of life. The aim of this study was to assess the effect of fructooligosaccharides (FOS) in the treatment of infants with constipation. This randomized, double-blind, placebo-controlled clinical trial included infants with constipation who were randomly assigned to one of two parallel groups: FOS or placebo. Either the FOS supplement or the placebo was added to the infant formula. Thirty-six infants completed the 4-week intervention. Therapeutic success occurred in 83.3% of the FOS group infants and in 55.6% of the control group infants (p = 0.073; one-tailed test). Compared with the control group, the FOS group exhibited a higher frequency of softer stools (p = 0.035) and fewer episodes of straining and/or difficulty passing stools (p = 0.041). At the end of the intervention, the mouth-to-anus transit time was shorter (22.4 and 24.5 h, p = 0.035), and the Bifidobacterium sp. count was higher (p = 0.006) in the FOS group. In conclusion, the use of FOS in infants with constipation was associated with significant improvement in symptoms, but the results showed no statistical significance regarding the success of the therapy compared with the control group. FOS was associated with reduced bowel transit time and higher counts of the genus Bifidobacterium in the stool. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants
Nutrients 2018, 10(10), 1556; https://doi.org/10.3390/nu10101556
Received: 25 September 2018 / Revised: 12 October 2018 / Accepted: 12 October 2018 / Published: 20 October 2018
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Abstract
Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs [...] Read more.
Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; <1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3′-sialyllactose and 6′-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle Microbiota and Derived Parameters in Fecal Samples of Infants with Non-IgE Cow’s Milk Protein Allergy under a Restricted Diet
Nutrients 2018, 10(10), 1481; https://doi.org/10.3390/nu10101481
Received: 21 September 2018 / Revised: 5 October 2018 / Accepted: 6 October 2018 / Published: 11 October 2018
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Abstract
Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal [...] Read more.
Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β1 levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessArticle Efficacy of an Oral Rehydration Solution Enriched with Lactobacillus reuteri DSM 17938 and Zinc in the Management of Acute Diarrhoea in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial
Nutrients 2018, 10(9), 1189; https://doi.org/10.3390/nu10091189
Received: 5 August 2018 / Revised: 22 August 2018 / Accepted: 27 August 2018 / Published: 1 September 2018
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Abstract
The efficacy of oral rehydration solution (ORS) enriched with Lactobacillus reuteri DSM 17938 and zinc in infants with acute gastroenteritis, is poorly defined. The aim of this double-blind, randomized, placebo-controlled study, was to assess the efficacy of an ORS enriched with Lactobacillus reuteri [...] Read more.
The efficacy of oral rehydration solution (ORS) enriched with Lactobacillus reuteri DSM 17938 and zinc in infants with acute gastroenteritis, is poorly defined. The aim of this double-blind, randomized, placebo-controlled study, was to assess the efficacy of an ORS enriched with Lactobacillus reuteri DSM 17938 and zinc (ORS+Lr&Z) in well-nourished, non-hospitalized infants with acute diarrhoea. Fifty one infants with acute diarrhoea were randomly assigned to receive either ORS+Lr&Z (28 infants, mean ± SD age 1.7 ± 0.7 years, 21 males), or standard ORS (ORSLr&Z; 23 infants, mean ± SD age 1.8 ± 0.7 years, 16 males). Stools volume and consistency were recorded pre- and posttreatment using the Amsterdam Infant Stool Scale and were compared between the two groups, as well as lost work/day care days, drug administration and need for hospitalization. Both groups showed reduction in the severity of diarrhoea on day two (p < 0.001) while, all outcomes showed a trend to be better in the ORS+Lr&Z group, without reaching statistical significance, probably due to the relatively small number of patients. No adverse effects were recorded. In conclusion, both ORS were effective in managing acute diarrhoea in well-nourished, non-hospitalized infants. ORS enriched with L. reuteri DSM 17938 and zinc was well tolerated with no adverse effects. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Review

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Open AccessFeature PaperReview Probiotics on Pediatric Functional Gastrointestinal Disorders
Nutrients 2018, 10(12), 1836; https://doi.org/10.3390/nu10121836
Received: 26 October 2018 / Revised: 22 November 2018 / Accepted: 27 November 2018 / Published: 29 November 2018
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Abstract
The potential association between gut microbiota perturbations and childhood functional gastrointestinal disturbances opens interesting therapeutic and preventive possibilities with probiotics. The aim of this review was to evaluate current evidence on the efficacy of probiotics for the management of pediatric functional abdominal pain [...] Read more.
The potential association between gut microbiota perturbations and childhood functional gastrointestinal disturbances opens interesting therapeutic and preventive possibilities with probiotics. The aim of this review was to evaluate current evidence on the efficacy of probiotics for the management of pediatric functional abdominal pain disorders, functional constipation and infantile colic. Thus far, no single strain, combination of strains or synbiotics can be recommended for the management of irritable bowel syndrome, functional abdominal pain or functional constipation in children. However, Lactobacillus reuteri DSM 17938 may be considered for the management of breastfed colic infants, while data on other probiotic strains, probiotic mixtures or synbiotics are limited in infantile colic. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
Open AccessReview Probiotics in Celiac Disease
Nutrients 2018, 10(12), 1824; https://doi.org/10.3390/nu10121824
Received: 30 September 2018 / Revised: 6 November 2018 / Accepted: 15 November 2018 / Published: 23 November 2018
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Abstract
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance [...] Read more.
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessReview Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases
Nutrients 2018, 10(11), 1723; https://doi.org/10.3390/nu10111723
Received: 15 October 2018 / Revised: 5 November 2018 / Accepted: 8 November 2018 / Published: 10 November 2018
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Abstract
The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent [...] Read more.
The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as “therapeutic microbiology”. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessReview Rationale of Probiotic Supplementation during Pregnancy and Neonatal Period
Nutrients 2018, 10(11), 1693; https://doi.org/10.3390/nu10111693
Received: 24 September 2018 / Revised: 31 October 2018 / Accepted: 3 November 2018 / Published: 6 November 2018
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Abstract
Probiotics are living microorganisms that confer a health benefit when administered in adequate amounts. It has been speculated that probiotics supplementation during pregnancy and in the neonatal period might reduce some maternal and neonatal adverse outcomes. In this narrative review, we describe the [...] Read more.
Probiotics are living microorganisms that confer a health benefit when administered in adequate amounts. It has been speculated that probiotics supplementation during pregnancy and in the neonatal period might reduce some maternal and neonatal adverse outcomes. In this narrative review, we describe the rationale behind probiotic supplementation and its possible role in preventing preterm delivery, perinatal infections, functional gastrointestinal diseases, and atopic disorders during early life. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
Open AccessReview Microbial and Nutritional Programming—The Importance of the Microbiome and Early Exposure to Potential Food Allergens in the Development of Allergies
Nutrients 2018, 10(10), 1541; https://doi.org/10.3390/nu10101541
Received: 30 September 2018 / Revised: 15 October 2018 / Accepted: 16 October 2018 / Published: 18 October 2018
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Abstract
The “microbiota hypothesis” ties the increase in allergy rates observed in highly developed countries over the last decades to disturbances in the gut microbiota. Gut microbiota formation depends on a number of factors and occurs over approximately 1000 days of life, including the [...] Read more.
The “microbiota hypothesis” ties the increase in allergy rates observed in highly developed countries over the last decades to disturbances in the gut microbiota. Gut microbiota formation depends on a number of factors and occurs over approximately 1000 days of life, including the prenatal period. During this period the microbiota helps establish the functional immune phenotype, including immune tolerance. The development of immune tolerance depends also on early exposure to potential food allergens, a process referred to as nutritional programming. This article elaborates on the concepts of microbial and nutritional programming and their role in the primary prevention of allergy. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessReview Filling the Gaps: Current Research Directions for a Rational Use of Probiotics in Preterm Infants
Nutrients 2018, 10(10), 1472; https://doi.org/10.3390/nu10101472
Received: 23 September 2018 / Revised: 6 October 2018 / Accepted: 8 October 2018 / Published: 10 October 2018
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Abstract
The use of probiotics among very low-birth-weight infants is constantly increasing, as probiotics are believed to reduce the incidence of severe diseases such as necrotizing enterocolitis and late-onset sepsis and to improve feeding tolerance. However, despite the enthusiasm towards these products in neonatal [...] Read more.
The use of probiotics among very low-birth-weight infants is constantly increasing, as probiotics are believed to reduce the incidence of severe diseases such as necrotizing enterocolitis and late-onset sepsis and to improve feeding tolerance. However, despite the enthusiasm towards these products in neonatal medicine, theoretical knowledge and clinical applications still need to be improved. The purpose of this review is to give an overview of the most important gaps in the current literature about potential uses of probiotics in preterm infants, highlighting promising directions for future research. Specifically, further well-designed studies should aim at clarifying the impact of the type of feeding (mother’s milk, donor milk, and formula) on the relationship between probiotic supplementation and clinical outcome. Moreover, future research is needed to provide solid evidence about the potential greater efficacy of multi-strain probiotics compared to single-strain products. Safety issues should also be addressed properly, by exploring the potential of paraprobiotics and risks connected to antibiotic resistance in preterm infants. Last, in light of increasing commercial and public interests, the long-term effect of routine consumption of probiotics in such a vulnerable population should be also evaluated. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
Open AccessReview Human Milk Oligosaccharides to Prevent Gut Dysfunction and Necrotizing Enterocolitis in Preterm Neonates
Nutrients 2018, 10(10), 1461; https://doi.org/10.3390/nu10101461
Received: 28 September 2018 / Revised: 4 October 2018 / Accepted: 5 October 2018 / Published: 8 October 2018
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Abstract
This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant [...] Read more.
This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant HMOs that serve as prebiotics and immunomodulators. Gut immaturity in preterm infants leads to difficulties in tolerating enteral feeding and bacterial colonization and a high sensitivity to NEC, particularly when breast milk is insufficient. Due to the immaturity of the preterm infants, their response to HMOs could be different from that in term infants. The concentration of HMOs in human milk is highly variable and there is no evidence to support a specifically adapted high concentration in preterm milk. Further, the gut microbiota is not only different but also highly variable after preterm birth. Studies in pigs as models for preterm infants indicate that HMO supplementation to formula does not mature the gut or prevent NEC during the first weeks after preterm birth and the effects may depend on a certain stage of gut maturity. Supplemented HMOs may become more important for gut protection in the preterm infants when the gut has reached a more mature phase. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessFeature PaperReview Lactobacillus rhamnosus GG in the Primary Prevention of Eczema in Children: A Systematic Review and Meta-Analysis
Nutrients 2018, 10(9), 1319; https://doi.org/10.3390/nu10091319
Received: 16 August 2018 / Revised: 4 September 2018 / Accepted: 14 September 2018 / Published: 18 September 2018
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Abstract
Current guidelines recommend the use of probiotics to reduce the risk of eczema. It remains unclear which strain(s) to use. We systematically evaluated data on the efficacy of Lactobacillus rhamnosus GG (LGG) supplementation prenatally and/or postnatally for the primary prevention of eczema. The [...] Read more.
Current guidelines recommend the use of probiotics to reduce the risk of eczema. It remains unclear which strain(s) to use. We systematically evaluated data on the efficacy of Lactobacillus rhamnosus GG (LGG) supplementation prenatally and/or postnatally for the primary prevention of eczema. The Cochrane Library, MEDLINE, and EMBASE databases were searched up to August 2018, with no language restrictions, for systematic reviews of randomized controlled trials (RCTs) and RCTs published afterwards. The primary outcome was eczema. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. Heterogeneity was explored using the I2 statistics. The GRADE criteria were used to assess the overall quality of evidence supporting the primary outcome. Seven publications reporting 5 RCTs (889 participants) were included. High to moderate certainty in the body of evidence suggests that LGG supplementation (regardless of the timing of administration) did not reduce the risk of eczema. There was also no consistent effect on other allergic outcomes. This meta-analysis shows that LGG was ineffective in reducing eczema. It does not support the general recommendation to use probiotics for preventing eczema, unless specific strains would be indicated. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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Open AccessReview Human Milk Oligosaccharides: 2′-Fucosyllactose (2′-FL) and Lacto-N-Neotetraose (LNnT) in Infant Formula
Nutrients 2018, 10(9), 1161; https://doi.org/10.3390/nu10091161
Received: 23 July 2018 / Revised: 9 August 2018 / Accepted: 14 August 2018 / Published: 24 August 2018
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Abstract
The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some [...] Read more.
The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother’s milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow’s milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
Open AccessReview Bacillus clausii for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nutrients 2018, 10(8), 1074; https://doi.org/10.3390/nu10081074
Received: 26 June 2018 / Revised: 30 July 2018 / Accepted: 8 August 2018 / Published: 12 August 2018
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Abstract
Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of [...] Read more.
Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of Bacillus clausii in the treatment of acute childhood diarrhea. The following electronic databases were systematically searched up to October 2017: MEDLINE (via PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and ClinicalTrials.gov. Only randomized controlled trials were included. The overall effect for the meta-analysis was derived by using a random effects model. Six randomized controlled trials (1298 patients) met the eligibility criteria. Data arising from pooled analysis showed that Bacillus clausii significantly reduced the duration of diarrhea (mean difference = −9.12 h; 95% confidence interval [CI]: −16.49 to −1.75, p = 0.015), and the duration of hospitalization (mean difference = −0.85 days; 95% CI: −1.56 to −0.15, p = 0.017), compared with control. There was a trend of decreasing stool frequency after Bacillus clausii administration compared with the control group (mean difference = −0.19 diarrheal motions; 95% CI: −0.43 to −0.06, p = 0.14). Bacillus clausii may represent an effective therapeutic option in acute childhood diarrhea, with a good safety profile. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
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