Ibero-Latin American clinical practice guideline for the use of biotics in pediatric gastroenterology, hepatology, and nutrition: probiotics chapter.

This article provides recommendations, developed by the Working Group (WG) on Probiotics of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition, for the use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) in children based on a systematic review of previously completed systematic reviews and of randomized controlled trials published subsequently to these reviews. The use of probiotics for the treatment of AAD is not covered. The recommendations were formulated only if at least 2 randomized controlled trials that used a given probiotic (with strain specification) were available. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation guidelines. If the use of probiotics for preventing AAD is considered because of the existence of risk factors such as class of antibiotic(s), duration of antibiotic treatment, age, need for hospitalization, comorbidities, or previous episodes of AAD diarrhea, the WG recommends using Lactobacillus rhamnosus GG (moderate QoE, strong recommendation) or Saccharomyces boulardii (moderate QoE, strong recommendation). If the use of probiotics for preventing Clostridium difficile-associated diarrhea is considered, the WG suggests using S boulardii (low QoE, conditional recommendation). Other strains or combinations of strains have been tested, but sufficient evidence is still lacking.

Probiotics for preventing antibiotic-associated diarrhea

A Gastroenterologist's Guide to Probiotics

Preterm birth, C-sections, antibiotics, and limited breastfeeding contribute to the increase in noncommunicable diseases. Our objective was to perform a descriptive review of probiotic use in pediatrics, focused on Lactobacillus rhamnosus GG. Certain probiotics have demonstrated to be effective in acute diarrhea and antibiotic-associated diarrhea. L. rhamnosus GG and Saccharomyces boulardii may shorten their duration and symptoms. L. reuteri DSM 17938 and L. rhamnosus GG were effective to manage infant colic. The use of this strain in infant formulas for cow's milk protein allergy may promote an earlier tolerance acquisition. In relation to the prevention of atopic dermatitis, the administration of L. rhamnosus GG during pregnancy reduced its development in the infant. The use of probiotics as adjuvants is a possibility to consider in current pediatric practice.

Celiac Disease: The Endocrine Connection

Probiotics are widely used in paediatrics, but efficacy varies by strain and indication. In 2023, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications issued strain-specific recommendations for gastrointestinal disorders. This review summarises studies published since 2024 to assess whether new evidence warrants changes to these recommendations. Lacticaseibacillus rhamnosus GG (LGG) and Saccharomyces boulardii are recommended for preventing antibiotic-associated diarrhoea. LGG, S. boulardii, Limosilactobacillus reuteri DSM 17938, or the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 may be considered in acute gastroenteritis. For infant colic, recommendations include L. reuteri DSM 17938 or Bifidobacterium lactis BB-12 in breast-fed infants; for functional abdominal pain, L. reuteri DSM 17938 or LGG. No probiotics are recommended for constipation. For prevention of necrotising enterocolitis, weak recommendations include LGG or a combination of B. infantis BB-02, B. lactis BB-12 and Streptococcus thermophilus TH-4. There is no recommendation for or against probiotic-supplemented formulas. Recent trials have not provided sufficient evidence to justify changes to the ESPGHAN recommendations. Evidence for probiotic use in paediatrics is confined to a few strains and indications. Larger multicentre studies with standardised preparations and clearly defined outcomes are still needed.

Probiotics Linked to 60% Drop in Antibiotic-Associated Diarrhea

There is growing evidence encouraging the use of probiotics in many conditions in children. However, given the wide number of probiotics available and contradictory data in the literature, the health-care provider is often faced with uncertainness about whether or not to use probiotics and which one(s) to choose. We here review current hypotheses regarding the efficacy and safety of probiotics and evaluate the available data on the use of probiotics in most common diseases in children. Considering that probiotics have strain-specific effects, we will focus on individual probiotic strains rather than on probiotics in general. Strain-specific efficacy was clearly demonstrated with Lactobacillus rhamnosus GG and Saccharomyces boulardii I-745 in the treatment of acute infectious diarrhea, Lactobacillus reuteri DSM 17938 in infantile colics, Lactobacillus rhamnosus GG, and VSL#3 in irritable bowel syndrome. In addition, encouraging results are seen for use of probiotics in necrotizing enterocolitis, food allergy, and nonalcoholic fatty liver disease. However, the data available for constipation are to be considered somewhat equivocal. The clinical relevance of these findings indicates that healthcare providers need to take strain-specificity and disease specificity of probiotics into consideration when recommending probiotic for their patients.

G.G.C. has received com M.C. has served on th served on the board o and Enteral Nutrition; her institution has rec collaborative and Prov pensation from Child L.A.G. has received c received compensatio employment, expert t stocks/stock options; LLC, consulted to No received or has grants Institutes of Health, th holds equity interest in has received compens Fibrosis Foundation; M Abbott Laboratories, Foundation, the Natio Diseases/National Ins ticals; E.A.R. has rece sionalism & Ethical institution has receive as the medical editor has received compen Pharmaceuticals, and Nutrition; J.T. has rec Pediatrics, Prometheu conflicts of interest. Copyright # 2012 by E Hepatology, and Nut Gastroenterology, He DOI: 10.1097/MPG.0b01

BackgroundAntibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic‐associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population.ObjectivesTo assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic‐associated diarrhea in children.To assess adverse events associated with the use of probiotics when co‐administered with antibiotics in children.Search strategyMEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched.Selection criteriaRandomized, parallel, controlled (placebo, active, or no treatment) trials comparing co‐administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years).Data collection and analysisMethodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea,a priorisensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic‐associated diarrhea, and antibiotic agent.Main resultsTen studies met the inclusion criteria. Trials included treatment with eitherLactobacilli spp.,Bifidobacterium spp.,Streptococcus spp., orSaccharomyces boulardiialone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains.The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non‐significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event.Authors' conclusionsProbiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g.,Lactobacillus GG,Lactobacillus sporogenes,Saccharomyces boulardiiat 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic‐associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.Plain language summaryIt is premature to routinely recommend probiotics for the prevention of pediatric antibiotic‐associated diarrhea (AAD)Studies of probiotics for the prevention of pediatric AAD. Ten studies were reviewed and provide the best evidence we have. Study quality was mostly good overall. The studies tested 1986 children (aged 0 to 18 years) who were receiving probiotics co‐administered with antibiotics to prevent AAD. The subjects received probiotics (Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination), placebo (fake pills), other treatments thought to prevent AAD (i.e. diosmectite or infant formula) or no treatment. The studies were short term and ranged in length from 15 days to 3 months.What is AAD and could probiotics work to prevent AAD? AAD occurs when antibiotics disturb the natural balance of "good" and "bad" bacteria in the intestinal tract causing harmful bacteria to sometimes multiply beyond their normal numbers. The symptoms of AAD may include frequent watery bowel movements and crampy abdominal pain. Probiotics are dietary supplements containing potentially beneficial bacteria or yeast. Probiotics are thought to restore the natural balance of bacteria in the intestinal tract.What did the studies show? An analysis that included only patients who completed the studies showed that probiotics may be effective for preventing AAD. However, a more conservative analysis that counted study drop‐outs as treatment failures did not show any differences between probiotic and comparison groups.How safe are probiotics? Probiotics were generally well tolerated and side effects occurred infrequently.What is the bottom line? Although current data are promising, there is insufficient evidence to routinely recommend the use of probiotics for the prevention of pediatric AAD.

Introducción: Los probióticos fueron descritos en el siglo 18 d.C, son microorganismos no patógenos vivos, han sido estudiados desde épocas ancestrales gracias a sus propiedades curativas y preventivas. A través del tiempo se ha logrado determinar con mayor exactitud el mecanismo de acción mediante el cual provocan un efecto beneficioso en los organismos, especialmente en patologías respiratorias, digestivas, urinarias y alérgicas. El presente trabajo se enfoca en la utilidad de los probióticos como terapia coadyuvante en patologías pediátricas.
 Objetivo: Evaluar de manera crítica la literatura científica reciente sobre los usos clínicos de los probióticos en pediatría.
 Material y métodos: Se realizó una revisión sistemática de la literatura científica publicada en el periodo 2015-2020. Se realizó una búsqueda en los sitios a continuación utilizando los siguientes términos: ‘‘probiotics,’’ ‘‘therapeutic uses of probiotics,’’ ‘‘clinical uses of probiotics,’’ ‘‘uses of probiotics,’’ ‘‘Lactobacillus,’’ ‘‘Bifidobacterium,’’ ‘‘Saccharomyces,’’ ‘‘probiotics in children,’’ history of prebiotics”, “probiotics in diarrhea”, “probiotics in urinary tract infection”, “probiotics in respiratory infections”, “Pediatric uses of probiotics”, en bases de datos: Medline, Cochrane Database of Systemic Review, New England Journal of Medicine, American Journal of Gastroenterology, Journal of Pediatric Gastroenterology Nutrition, BMJ, Oxford academic, Elsevier, US National Library of Medicine National Institutes of Health.
 Resultados: Los referentes teóricos analizados permitieron determinar los aspectos más relevantes de las aplicaciones clínicas de los probióticos en pediatría: gastroenteritis agudas virales, diarrea persistente, diarrea asociada a antibióticos, prevención de diarrea por Clostridium difficile, tratamiento coadyuvante de erradicación de Helicobacter pylori, Enfermedad inflamatoria intestinal: reservoritis y Enterocolitis Necrotizante.
 Conclusiones: La administración de probióticos se ha incrementado como tratamiento coadyuvante en múltiples patologías y se ha demostrado los pocos o nulos efectos adversos en los pacientes pediátricos, se estima que el riesgo de desarrollar bacteremia por lactobacilos ingeridos es inferior a uno por un millón de consumidores, lo que refuerza su alta seguridad de uso en los pacientes pediátricos. La investigación sobre los probióticos y sus relaciones con la microbiota continúan aportando nuevos conocimientos acerca de sus mecanismos y su impacto en la salud, lo que ha permitido profundizar sobre sus principales potencialidades, basadas en el antagonismo antimicrobiano, restauración del balance de la microbiota y mejoría a la respuesta inmune. Hay recomendación seria sobre su beneficio en las diarreas agudas infecciosas, la diarrea asociada a antibióticos, enterocolitis necrosante en el recién nacido de bajo peso y prematuridad, su influencia en el sistema inmune y en otras enfermedades intestinales, al mejorar la resistencia a las infecciones y los estados de alergia, en especial, en los lactantes y niños pequeños. Sin embargo, en infección del tracto urinario e infecciones respiratorias no hay evidencia concluyente que recomiende el uso de probióticos. Se sugiere incorporar los probióticos al cuadro nacional de medicamentos, porque al quedar demostrado el acortamiento en la duración de enfermedad diarreica aguda, ello reduciría la estancia hospitalaria de pacientes pediátricos, con la consiguiente reducción en el gasto del sector salud

Chapter 21 - Probiotics in pediatrics

Assessing worldwide research activity on probiotics in pediatrics using Scopus database: 1994–2014

State of Research in Pediatric Gastroenterology, Hepatology, and Nutrition: 2010 and Beyond

Does Lactobacillus GG prevent antibiotic-associated diarrhea in children?