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1.
Early-Life Respiratory Infections in Infants with Cow's Milk Allergy: An Expert Opinion on the Available Evidence and Recommendations for Future Research.
Fiocchi, A, Knol, J, Koletzko, S, O'Mahony, L, Papadopoulos, NG, Salminen, S, Szajewska, H, Nowak-Węgrzyn, A
Nutrients. 2021;(11)
Abstract
Acute respiratory infections are a common cause of morbidity in infants and young children. This high rate of respiratory infections in early life has a major impact on healthcare resources and antibiotic use, with the associated risk of increasing antibiotic resistance, changes in intestinal microbiota composition and activity and, consequently, on the future health of children. An international group of clinicians and researchers working in infant nutrition and cow's milk allergy (CMA) met to review the available evidence on the prevalence of infections in healthy infants and in those with allergies, particularly CMA; the factors that influence susceptibility to infection in early life; links between infant feeding, CMA and infection risk; and potential strategies to modulate the gut microbiota and infection outcomes. The increased susceptibility of infants with CMA to infections, and the reported potential benefits with prebiotics, probiotics and synbiotics with regard to improving infection outcomes and reducing antibiotic usage in infants with CMA, makes this a clinically important issue that merits further research.
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2.
A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy.
Guillemard, E, Poirel, M, Schäfer, F, Quinquis, L, Rossoni, C, Keicher, C, Wagner, F, Szajewska, H, Barbut, F, Derrien, M, et al
Nutrients. 2021;(9)
Abstract
Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.
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3.
Post hoc analysis of fecal samples from responders and non-responders to Lactobacillus reuteri DSM 17938 intervention.
Szymanski, H, Mlynarz, P, Qasem, B, Korzeniowska-Kowal, A, Szponar, B, Kałwak-Baran, M, Szajewska, H
Acta biochimica Polonica. 2020;(3):393-399
Abstract
We compared fecal samples from responders and non-responders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a "metabolic niche", including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus, would determine the response to probiotic treatment. These findings need to be confirmed, but identification of some differences in the fecal metabolomics and the calprotectin level suggests that further studies are warranted.
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4.
Probiotics for the prevention of antibiotic-associated adverse events in children-A scoping review to inform development of a core outcome set.
Łukasik, J, Guo, Q, Boulos, L, Szajewska, H, Johnston, BC
PloS one. 2020;(5):e0228824
Abstract
INTRODUCTION Routine use of probiotics during antibiotic therapy in children remains a subject of discussion. To facilitate synthesis of individual study results and guideline formulation, it is important to assess predefined, similar, and clinically important outcomes. Core outcome sets are a proposed solution for this issue. The aim of this review was to document choice, design, and heterogeneity of outcomes in studies that assessed the effects of probiotics used for the prevention of antibiotic-associated adverse events in children. METHODS A scoping literature search covering three major databases was performed. Studies that evaluated oral probiotics' use concomitant with antibiotic therapy in children were included. Data on outcome definitions, measurement instruments, and follow-up were extracted. The outcomes were assigned to predefined core areas and domains. Data were analyzed descriptively. RESULTS Thirty-seven studies were included in this review. Diarrhea, the most commonly reported outcome, had diagnostic criteria clearly defined only in 21 studies. In total, 16 different definitions of diarrhea were identified. Diarrhea duration, severity, and etiology were reported in 9, 4, and 7 studies, respectively. Twenty studies assessed gastrointestinal symptoms other than diarrhea. Seven studies reported outcomes related to resource use or the economic impact of the intervention. Only 2 studies assessed outcomes related to life impact. None of the studies predefined adverse events of probiotic use. CONCLUSIONS Identified outcomes were characterized by substantial heterogeneity. The majority of outcomes were not designed to evaluate endpoints of real-life relevance. Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making.
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5.
Postbiotics for Preventing and Treating Common Infectious Diseases in Children: A Systematic Review.
Malagón-Rojas, JN, Mantziari, A, Salminen, S, Szajewska, H
Nutrients. 2020;(2)
Abstract
Postbiotics have recently been tentatively defined as bioactive compounds produced during a fermentation process (including microbial cells, cell constituents and metabolites) that supports health and/or wellbeing. Postbiotics are currently available in some infant formulas and fermented foods. We systematically reviewed evidence on postbiotics for preventing and treating common infectious diseases among children younger than 5 years. The PubMed, Embase, SpringerLink, and ScienceDirect databases were searched up to March 2019 for randomized controlled trials (RCTs) comparing postbiotics with placebo or no intervention. Seven RCTs involving 1740 children met the inclusion criteria. For therapeutic trials, supplementation with heat-killed Lactobacillus acidophilus LB reduced the duration of diarrhea (4 RCTs, n = 224, mean difference, MD, -20.31 h, 95% CI -27.06 to -13.57). For preventive trials, the pooled results from two RCTs (n = 537) showed that heat-inactivated L. paracasei CBA L74 versus placebo reduced the risk of diarrhea (relative risk, RR, 0.51, 95% CI 0.37-0.71), pharyngitis (RR 0.31, 95% CI 0.12-0.83) and laryngitis (RR 0.44, 95% CI 0.29-0.67). There is limited evidence to recommend the use of specific postbiotics for treating pediatric diarrhea and preventing common infectious diseases among children. Further studies are necessary to determine the effects of different postbiotics.
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6.
Prophylactic use of probiotics for gastrointestinal disorders in children.
Perceval, C, Szajewska, H, Indrio, F, Weizman, Z, Vandenplas, Y
The Lancet. Child & adolescent health. 2019;(9):655-662
Abstract
The gastrointestinal microbiome is a hot topic in clinical research. Beneficial effects of selected probiotics in the prevention of gastrointestinal disorders are mainly restricted to acute gastroenteritis, antibiotic-associated diarrhoea, infantile colic, and necrotising enterocolitis. However, no broad consensus exists to recommend the use of probiotics in the prevention of these conditions, mainly because of the different design of the studies done so far, resulting in little evidence for specific strains, dosages, and indications. More well designed studies are needed before recommendations can be proposed. At this stage, the evidence is insufficient to recommend the routine use of probiotics in infants and children for the prevention of gastrointestinal disorders.
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7.
Effect of a multispecies probiotic on reducing the incidence of antibiotic-associated diarrhoea in children: a protocol for a randomised controlled trial.
Łukasik, J, Szajewska, H
BMJ open. 2018;(5):e021214
Abstract
INTRODUCTION Certain individual probiotic strains have been proven to be effective in reducing the risk of antibiotic-associated diarrhoea (AAD). However, the effects of using multispecies probiotics (MPs) remain unclear. We aim to assess the effectiveness of a specific MP preparation (Winclove 612) in reducing the incidence of AAD in children. METHODS AND ANALYSIS A total of 350 children aged 6 months to 18 years, undergoing antibiotic treatment, will be randomly allocated to receive either a MP consisting of two strains of Bifidobacterium (B. bifidum W23 and B. lactis W51) and six strains of Lactobacillus (L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71 and L. salivarius W24) at a total dose of 1010 colony-forming units daily, or a placebo, from the first day of antibiotic treatment until 7 days after antibiotic cessation, up to a maximum of 17 days. The primary outcome will be the incidence of AAD, defined as ≥3 loose or watery stools (a score of A on the Amsterdam Infant Stool Scale or a score of 5-7 on the Bristol Stool Form scale) in 24 hours, caused either by Clostridium difficile or of otherwise unexplained aetiology, occurring during the intervention period. The secondary outcomes will include the incidence of AAD according to alternative definitions; the incidence of any kind of diarrhoea; the duration of diarrhoea; the need for hospitalisation; intravenous rehydration or discontinuation of antibiotic treatment due to diarrhoea; adverse events; and the intestinal microbiota composition. ETHICS AND DISSEMINATION The study protocol is approved by the Ethics Committee of the Medical University of Warsaw. The findings will be published in a peer-reviewed journal and submitted to relevant conferences. DATE AND PROTOCOL VERSION IDENTIFIER 14/10/2017. TRIAL REGISTRATION NUMBER NCT03334604; Pre-results.
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8.
Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis.
van den Akker, CHP, van Goudoever, JB, Szajewska, H, Embleton, ND, Hojsak, I, Reid, D, Shamir, R, ,
Journal of pediatric gastroenterology and nutrition. 2018;(1):103-122
Abstract
OBJECTIVES Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy. METHODS A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA. RESULTS Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains. CONCLUSIONS This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.
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9.
Commercial Probiotic Products: A Call for Improved Quality Control. A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics.
Kolaček, S, Hojsak, I, Berni Canani, R, Guarino, A, Indrio, F, Orel, R, Pot, B, Shamir, R, Szajewska, H, Vandenplas, Y, et al
Journal of pediatric gastroenterology and nutrition. 2017;(1):117-124
Abstract
Probiotics have been proposed for a number of indications ranging from the hypothetical long-term immunomodulatory effects to proven benefits in the management of different clinical conditions.An increasing number of commercial products containing probiotics are available. In those products, irrespective if it is food, food supplement, medical food, or drug, the probiotic microorganisms have to be present in a sufficient number by the end of the shelf-life, to pass through the gastrointestinal tract resisting acid and bile, to colonize the gut, and to retain functional properties required to obtain the suggested beneficial effect. Finally, it should be contamination-free.Studies organized worldwide and summarized in this article have shown that inconsistencies and deviations from the information provided on the product label are surprisingly common. Frequently strains are misidentified and misclassified, products are occasionally contaminated, sometimes with even facultative or obligatory pathogens, strains are not viable, the labeled number of colonies cannot be verified, or the functional properties are diminished to the extent that preclude the proposed health benefit. As the probiotic preparations are commonly used for a wide range of conditions, the aim of the Working Group was to summarize results of the studies looking into the quality of the probiotic products and to raise the awareness of the important issue of their quality control.Based on the results obtained, we strongly suggest a more stringent quality control process. This process should ensure that the probiotic content as mentioned on the label meets the actual content throughout the shelf life of the product, while no contamination is present.
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10.
To add or not to add probiotics to infant formulae? An updated systematic review.
Skórka, A, Pieścik-Lech, M, Kołodziej, M, Szajewska, H
Beneficial microbes. 2017;(5):717-725
Abstract
We updated evidence on the effects of the administration of probiotic-supplemented infant formulae (IF) compared with unsupplemented IF. Five databases were searched up to September 2016 for randomised controlled trials. Twenty publications were identified, including five new RCTs. Supplementation of IF with Bifidobacterium lactis Bb12, either alone or with Streptococcus thermophilus, had no effect on growth, respiratory illness, antibiotic use, stool frequency or consistency. However, there was a significant reduction in the number of episodes of gastrointestinal infections (Bb12) and a lower frequency of colic or irritability (when both strains were used). Lactobacillus johnsonii La1 had no effect on growth, gastrointestinal infections, or respiratory illness episodes. There were no effects of supplementation of IF with Bifidobacterium longum BL999, alone or with Lactobacillus rhamnosus LPR. L. rhamnosus GG was associated with better growth; it had no effect on colic/crying, or irritability, and it was associated with greater indexes of loose stools and a higher defecation frequency. Lactobacillus reuteri ATCC 55730 had no effect on growth, colic, crying, irritability, respiratory illness, antibiotic use, stool frequency, or stool consistency; however, it reduced the number of episodes of diarrhoea. L. reuteri DSM 17938 had no effect on growth, night-time sleeping, or flatulence, but it reduced the number of spitting episodes. Lactobacillus salivarius CEC5713 had no effect on growth, colic, crying, or irritability; however, it resulted in a significant reduction in the rate of diarrhoea and the number of episodes of respiratory symptoms. In conclusion, the administration of probiotic-supplemented formulae to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some beneficial clinical effects are possible; however, there is no existing robust evidence to recommend their routine use. The latter conclusion may reflect the small amount of data on a specific probiotic strain(s) and outcomes, rather than a genuine lack of an effect.