ABSTRACT: The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants. Streptococcus thermophilus, Lactobacillus reuteri DSM 17938, Bifidobacterium breve (BC50), Bifidobacterium lactis Bb12, Lactobacillus fermentum (CECT5716), and Lactobacillus rhamnosus GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.
OBJECTIVE: The dogma of probiotic strain-specificity is widely accepted. However, only the genus- and species-specific effects of probiotics are supported by evidence from clinical trials. The aim of this rapid review was to assess clinical evidence supporting the claim that the efficacy of probiotics in the pediatric population is strain-specific.
METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched (up to August 2022) for randomized controlled trials (RCTs) conducted in children aged 0-18 years evaluating the effects of prophylactic or therapeutic administration of probiotics (well-characterized at the strain level) for conditions such as antibiotic-associated diarrhea, acute diarrhea, necrotizing enterocolitis, respiratory tract infections, Helicobacter pylori infection, and atopic dermatitis. To allow evaluation of strain-specificity, a trial could only be included in the review if at least one additional RCT assessed the effect of a different strain of the same species against the same comparator. RCTs without proper strain-level data were excluded. In the absence of identifying head-to-head strain vs. strain RCTs, indirect comparisons were made between interventions.
RESULTS: Twenty-three RCTs were eligible for inclusion. Out of the 11 performed comparisons, with one exception (two L. paracasei strains in reducing atopic dermatitis symptoms), no significant differences between the clinical effects of different strains of the same probiotic species were found.
CONCLUSIONS: Head-to-head comparison is an optimal study design to compare probiotic strains, but such comparisons are lacking. Based on indirect comparisons, this rapid review demonstrates insufficient clinical evidence to support or refute the claim that probiotic effects in children are strain-specific.
Wheezing, asthma, and respiratory infections (RTI) are among the most common causes of morbidity in children and their economic and social burden could be significantly reduced by specific prevention strategies. Epidemiological studies suggest that lower levels of some nutrients are associated with higher prevalence of these conditions, but the possible protective effect of early supplementation with these nutrients has not yet been established. Aim of our review is to synthetize the available scientific evidence on the role of supplementation with pre- and probiotics, vitamin D, fish and poly-unsaturated fatty acids (PUFA), vitamin A, C, and E, given during the first year of life, in the prevention of wheezing, asthma and RTI. We searched studies published on this topic in the PubMed database between January 2000 and September 2021. As for pre- and probiotics, most of the studies showed that an early supplementation had no protective effect toward the development of asthma and wheezing, while conflicting results were reported on their role in the reduction of RTI. As for vitamin D, the available data suggest that early and regular (on a daily or weekly base) supplementation of vitamin D during infancy could have a role in the prevention of RTI, while most studies showed no effect in the prevention of wheezing or asthma. Finally, early introduction of fish in the diet in most studies has proved protective toward wheezing and asthma development.
BACKGROUND: Probiotics can improve immune function for prevention and management of viral infections like SARS-CoV-2 infection (COVID-19 disease).
METHODS: We searched on PubMed, EMBASE, Google Scholar, Science Direct, Scopus, and Web of Science up to May 2020 to identify interventional & observational studies documenting the effects of probiotics on incidence, severity, duration, and other clinical manifestations of viral infections especially SARS-CoV-2-induced.
RESULTS: From a total of 91 records, 24 studies were obtained and classified into three domains based on the efficacy of probiotics on 1) shortening the period and severity of infections (n=9), 2) incidence (n=6), and 3) Other clinical complications that may be followed by viral disorders (n=9). Identified probiotics have positive effects on the mentioned domains.
CONCLUSION: Based on the evidence, some probiotic strains may be useful in SARS-CoV-2 infection; randomized trials are needed to show the facts.
Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence). None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors' conclusions: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD, based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.
Antecedentes: La bacteria Clostridium difficile es una de las principales causas de diarrea infecciosa. Se trata de una vara anaeróbica, grampositiva y formadora de esporas, responsable de una significativa morbilidad y mortalidad, especialmente entre los ancianos hospitalizados. El manejo estándar de la diarrea asociada a C. difficile (CDAD) consiste en interrumpir un antibiótico causal, corregir el desequilibrio líquido-electrolitos e iniciar un tratamiento antibiótico para CDAD. Los métodos alternativos para la prevención de CDAD incluyen probióticos. Esta revisión sistemática proporcionará un resumen exhaustivo e imparcial de la investigación disponible sobre la efectividad de los probióticos en la disminución de la incidencia de diarrea infecciosa en pacientes ancianos hospitalizados. OBJETIVOS: Realizar una revisión sistemática para determinar la mejor evidencia disponible relacionada con la efectividad de probióticos en la prevención de CDAD en pacientes ancianos hospitalizados. La pregunta de la revisión era: ¿son probióticos eficaces en la disminución de la incidencia de CDAD en pacientes ancianos hospitalizados? CRITERIOS DE INCLUSIÓN TIPOS DE PARTICIPANTES: En la presente revisión se incluyeron estudios de participantes que tenían 60 años o más y que residían en centros de cuidados agudos y postoperatorios que estaban recibiendo o estaban planeando someterse a tratamiento antibiótico para el manejo de cualquier condición infecciosa, . TIPOS DE INTERVENCIÓN (S): La revisión actual incluyó estudios que evaluaron la efectividad de los probióticos para la prevención de CDAD en pacientes ancianos hospitalizados en centros de atención aguda y post-aguda en comparación con la atención habitual. RESULTADOS: La revisión actual incluyó estudios que examinaron las siguientes medidas de resultado: incidencia o recaída de CDAD. Los casos de CDAD se definieron por la presencia de diarrea y se verificaron por resultados positivos para el inmunoensayo enzimático de heces para las toxinas A y B. TIPOS DE ESTUDIOS: La revisión actual incluyó únicamente diseños de estudios experimentales, incluidos ensayos controlados aleatorios. ESTRATEGIA DE BÚSQUEDA: La estrategia de búsqueda incluyó estudios publicados en inglés entre 1978, cuando se informó el primer caso de CDAD y 2015. EVALUACIÓN DE LA CALIDAD METODOLÓGICA: Los trabajos seleccionados para su recuperación fueron evaluados por dos revisores independientes para la calidad metodológica antes de la inclusión en la revisión Utilizando instrumentos estandarizados de evaluación crítica del Joanna Briggs Institute (JBI). EXTRACCIÓN DE LOS DATOS: Los datos se extrajeron de los documentos incluidos en la revisión utilizando la herramienta de extracción de datos estandarizada del Meta-Análisis del JBI del instrumento de evaluación y revisión de estadísticas. Los datos extraídos incluían detalles específicos sobre las intervenciones, las poblaciones, los métodos de estudio y los resultados de importancia para la pregunta de revisión y los objetivos específicos. SÍNTESIS DE DATOS: Los datos cuantitativos se agruparon utilizando metanálisis estadístico. Los tamaños del efecto se expresaron como odds ratios y sus intervalos de confianza del 95% se calcularon para determinar si el tratamiento con probióticos era superior al placebo en la reducción de la incidencia de CDAD. La heterogeneidad se evaluó utilizando la estadística I estándar. Resultados Se incluyeron cinco estudios en la revisión. Los resultados del estudio individual fueron contradictorios, incluyendo resultados no significativos para cuatro estudios y resultados estadísticamente significativos en uno que demostró menos casos de CDAD entre los pacientes que recibieron probióticos en comparación con placebo. El metanálisis indicó que no hubo diferencias estadísticamente significativas en la incidencia de CDAD en pacientes ancianos hospitalizados que tomaban probióticos en comparación con un placebo. Conclusión: No se encontró que los probióticos fueran más eficaces que el placebo para reducir la incidencia de CDAD en pacientes ancianos hospitalizados. Sin embargo, los estudios que demuestren resultados mejorados deben ser examinados para determinar las necesidades futuras de investigación. Los estudios variaron con respecto a la dosis, frecuencia, método de administración (bebidas probióticas frente a cápsula), duración de la administración y número de cepas de bacterias administradas. Se necesitan más estudios para evaluar la efectividad de los probióticos para la prevención del CDAD en esta población. Se necesitan ensayos clínicos con métodos de administración basados en evidencia y metanálisis que reúnan los resultados de los estudios con metodologías congruentes para poder sacar conclusiones sobre la efectividad de la administración de probióticos para la prevención del CDAD.
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.
Antecedentes: La diarrea asociada a antibióticos (AAD) es un problema común en adultos y pacientes de edad avanzada debido al uso generalizado de antibióticos en esta población. Múltiples revisiones sistemáticas anteriores han demostrado una asociación entre los probióticos específicos y la disminución de la AAD, especialmente en los niños. Como no hay un análisis específico sobre los pacientes de edad avanzada, decidimos centrarnos en los adultos, especialmente los ancianos. MÉTODOS: Se realizó una revisión sistemática de la literatura sobre el uso de probióticos en el tratamiento de AAD en adultos (18-64 años) y sujetos ancianos (≥65 años). Se identificaron 436 artículos que cumplían con los criterios de búsqueda. Treinta ensayos controlados aleatorios cumplieron los criterios de inclusión predefinidos y se incluyeron en el metanálisis. RESULTADOS: Hubo una heterogeneidad considerable entre los ensayos (P <0,001); Así, se realizaron análisis de subgrupos. El metanálisis dio como resultado un riesgo relativo (RR) combinado de AAD de 0,69 (intervalo de confianza del 95% [IC del 95%]: 0,62-0,76) en un modelo de efectos fijos y 0,58 (IC del 95%: 0,48-0,71) en un Modelo de efectos aleatorios, en comparación con placebo. La asociación positiva entre la ingesta de probióticos y el riesgo reducido de AAD se observó en adultos (RR, 0,47; IC del 95%: 0,4-0,56). Por el contrario, en pacientes ancianos, no hubo efecto positivo (RR, 0,94; IC del 95%: 0,76-1,15) del uso de probióticos y AAD. Conclusión: En resumen, los resultados de nuestro metanálisis sugieren que la administración de probióticos adjuntos está asociada con un menor riesgo de AAD en adultos, pero no en personas de edad avanzada.
INTRODUCCIÓN: La infección por Clostridium difficile (CDI) es la principal causa de diarrea asociada a antibióticos. CDI ha aumentado en la incidencia y gravedad en la última década, y es un problema de salud mundial cada vez mayor asociado con los costos de atención de salud sustanciales y la morbilidad y la mortalidad significativa. Este metanálisis examina el impacto de los probióticos en la incidencia de diarrea asociada a Clostridium difficile (CDAD) en niños y adultos, tanto en hospitales como en centros ambulatorios. MÉTODOS: Se realizó una búsqueda bibliográfica exhaustiva de todos los ensayos controlados aleatorios publicados (ECA) que evaluaron el uso de probióticos en la prevención de la CDAD en pacientes que recibieron antibióticos y se analizó la incidencia de CDAD. RESULTADOS: Se analizaron 26 ECA en los que participaron 7.957 pacientes. El uso de probióticos redujo significativamente el riesgo de desarrollar CDAD en un 60,5% (riesgo relativo [RR] = 0,395; intervalo de confianza del 95% [IC], 0,294-0,531; P <0,001). Los probióticos resultaron beneficiosos en adultos y niños (59,5% y 65,9% de reducción), especialmente entre los pacientes hospitalizados. Lactobacillus, Saccharomyces y una mezcla de probióticos fueron beneficiosos para reducir el riesgo de desarrollar CDAD (63,7%, 58,5% y 58,2% de reducción). CONCLUSIÓN: La suplementación probiótica se asocia con una reducción significativa en el riesgo de desarrollar CDAD en pacientes que reciben antibióticos. Estudios adicionales son necesarios para determinar la dosis óptima y la tensión de probióticos.
The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants. Streptococcus thermophilus, Lactobacillus reuteri DSM 17938, Bifidobacterium breve (BC50), Bifidobacterium lactis Bb12, Lactobacillus fermentum (CECT5716), and Lactobacillus rhamnosus GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.
