Probiotici u pedijatrijskoj gastroenterologiji

INTRODUCTION Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (1). In paediatric gastroenterology, their use has expanded substantially in recent years, driven by an increasing understanding of the role of the gut microbiota in the pathogenesis of various gastrointestinal diseases. However, numerous studies have demonstrated that the effects of probiotics cannot be considered a class effect of all products, but are strictly strain-specific and dependent on dose, duration of administration, and the specific clinical indication. This has direct implications for clinical practice, as probiotics that are effective for one indication may not be effective for another. The 2023 recommendations of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) represent the most comprehensive and methodologically robust evaluation of the evidence regarding the use of probiotics in children with gastrointestinal disorders (2). This document systematically analysed randomized controlled trials (RCTs), meta-analyses, and systematic reviews using the GRADE methodology, allowing an objective assessment of the quality of evidence and strength of recommendations. More recent publications largely confirm these conclusions, emphasizing the need for a critical approach and discouraging uncritical, routine use of probiotics in everyday paediatric practice. GASTROENTEROLOGICAL INDICATIONS FOR PROBIOTIC USE Acute gastroenteritis Acute gastroenteritis is one of the most common indications for probiotic use in children. The ESPGHAN document analysed more than 30 randomized controlled trials involving several thousand children of different ages and with various causes of diarrhoea. The best-documented probiotic strains are Lacticaseibacillus rhamnosus GG (LGG), Saccharomyces (S.) boulardii, and Limosilactobacillus (L.) reuteri DSM 17938. Meta-analyses indicate that these strains may reduce the duration of diarrhoea by approximately 20–24 hours, decrease the need for hospitalization, and shorten the length of hospital stay (3–6). However, heterogeneity among studies, differences in dosage and duration of treatment, and changes in the epidemiology of gastroenteritis—particularly following the introduction of rotavirus vaccination—limit the clinical applicability of these findings. Therefore, probiotics are recommended only as an adjunct to standard therapy (oral rehydration), not as a replacement for established treatment measures. Antibiotic-associated diarrhoea (AAD) Antibiotic-associated diarrhoea is a common adverse effect of antibiotic therapy, particularly in young children and hospitalized patients. Analysis of more than 20 RCTs and several large meta-analyses has shown that probiotics, especially LGG and S. boulardii, can reduce the risk of AAD from approximately 19% to 8–10% (7, 8). The effect is particularly pronounced when high doses (≥5 × 10⁹ CFU/day) are used and in children with additional risk factors, such as prolonged antibiotic treatment, hospitalization, or comorbidities. These probiotic strains are recommended to be initiated early, ideally at the start of antibiotic therapy. Nevertheless, there are currently no clear recommendations for routine probiotic use in all children receiving antibiotics, and a selective approach targeting high-risk children appears more pragmatic. Prevention of nosocomial diarrhoea Nosocomial diarrhoea represents a significant problem in hospital settings, particularly in paediatric wards. More than 10 studies, primarily involving hospitalized young children, have been analysed. The strongest evidence supports the use of LGG, which has been shown to reduce the incidence of hospital-acquired diarrhoea, particularly rotavirus-associated diarrhoea (9, 10). In contrast, L. reuteri DSM 17938 has not demonstrated consistent benefit in this indication and is therefore not recommended for the prevention of nosocomial diarrhoea. Functional gastrointestinal disorders (disorders of gut–brain interaction) Infantile colic is a functional disorder with a substantial impact on the quality of life of the entire family. More than 15 RCTs and several meta-analyses have evaluated the efficacy of probiotics in this condition (11–20). The strongest evidence supports the use of L. reuteri DSM 17938 in breastfed infants, in whom it significantly reduces crying time and increases the proportion of infants achieving clinically meaningful improvement. Bifidobacterium (B.) lactis BB-12 has also shown beneficial effects, although fewer studies are available. In formula-fed infants, evidence remains limited and inconsistent. As no causal therapy exists for pain-related functional gastrointestinal disorders in older children, a number of studies have investigated the effects of probiotics in functional abdominal pain (FAP) and irritable bowel syndrome (IBS). Approximately 15–20 studies including children diagnosed according to Rome IV criteria have been analysed (21–23). Probiotics—particularly L. reuteri DSM 17938 in FAP and LGG in IBS—have demonstrated moderate reductions in pain intensity and frequency, but without a clear impact on quality of life or long-term outcomes. Due to heterogeneity and variability in study results, recommendations for probiotic use in these indications are weak. For functional constipation in children, more than 10 RCTs are available, but results are inconsistent (21, 24, 25). Most studies have not demonstrated clinically meaningful improvements compared with placebo, either in stool frequency or subjective symptom relief. Consequently, probiotics are not recommended as a standard component of therapy for functional constipation. Helicobacter pylori infection Approximately 10 studies have investigated the use of probiotics as adjuncts to eradication therapy (26, 27). Saccharomyces boulardii has been shown to reduce treatment-related adverse effects and to slightly increase eradication rates, although without achieving optimal eradication outcomes. Chronic inflammatory bowel disease (ulcerative colitis and Crohn’s disease) In the paediatric population, there are very few high-quality RCTs evaluating the efficacy of probiotics in the treatment of chronic inflammatory bowel disease. Most available evidence is derived from adult studies, which limits its applicability to children. At present, there is insufficient evidence to support routine probiotic use in paediatric IBD (2). Coeliac disease, small intestinal bacterial overgrowth (SIBO), and pancreatitis Available studies in these indications are scarce, small, and heterogeneous. There is insufficient evidence to recommend probiotics as part of standard clinical practice (2). CONCLUSION Probiotics have a role in selected areas of paediatric gastroenterology, but their use must be strictly indication-specific and evidence-based. The greatest benefit has been documented in acute gastroenteritis, prevention of antibiotic-associated diarrhoea, and infantile colic, whereas evidence for other indications is limited or lacking. Appropriate use requires careful selection of the probiotic strain, dose, and duration of therapy, as well as the use of products of verified quality.