Probiotics and Antibiotic-Induced Microbial Aberrations in Children: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Probiotics are often considered in children to prevent antibiotic-associated diarrhea. However, the underlying mechanistic effects and impact of probiotics on antibiotic-induced microbiota changes are not well understood. Objective: To investigate the effects of a multispecies probiotic on the gut microbiota composition in children receiving antibiotics. Design, Setting, and Participants: This is a secondary analysis of a randomized, quadruple-blind, placebo-controlled clinical trial from February 1, 2018, to May 31, 2021, including 350 children receiving broad-spectrum antibiotics in the inpatient and outpatient settings. Patients were followed up until 1 month after the intervention period. Fecal samples and data were analyzed between September 1, 2022, and February 28, 2023. Eligibility criteria included 3 months to 18 years of age and recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics. In total, 646 eligible patients were approached and 350 participated in the trial. Intervention: Participants were randomly assigned to receive daily placebo or a multispecies probiotic formulation consisting of 8 strains from 5 different genera during antibiotic treatment and for 7 days afterward. Main Outcomes and Measures: Fecal stool samples were collected at 4 predefined times: (1) inclusion, (2) last day of antibiotic use, (3) last day of the study intervention, and (4) 1 month after intervention. Microbiota analysis was performed by 16S ribosomal RNA gene sequencing. Results: A total of 350 children were randomized and collected stool samples from 88 were eligible for the microbiota analysis (54 boys and 34 girls; mean [SD] age, 47.09 [55.64] months). Alpha diversity did not significantly differ between groups at the first 3 times. Shannon diversity (mean [SD], 3.56 [0.75] vs 3.09 [1.00]; P = .02) and inverse Simpson diversity (mean [SD], 3.75 [95% CI, 1.66-5.82] vs -1.31 [95% CI, -3.17 to 0.53]; P = 1 × 10-4) indices were higher in the placebo group compared with the probiotic group 1 month after intervention. Beta diversity was not significantly different at any of the times. Three of 5 supplemented genera had higher relative abundance during probiotic supplementation, but this difference had disappeared after 1 month. Conclusions and Relevance: The studied probiotic mixture had minor and transient effects on the microbiota composition during and after antibiotic treatment. Further research is needed to understand their working mechanisms in manipulating the microbiome and preventing antibiotic-associated dysbiosis and adverse effects such as antibiotic-associated diarrhea. Trial Registration: ClinicalTrials.gov Identifier: NCT03334604.

Effect of probiotic supplementation on the gut microbiota in very preterm infants: a systematic review.

OBJECTIVE: There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development. DESIGN: A systematic review in Medline, Embase, Cochrane Library, CINAHL and Web of Science. SETTING: Neonatal intensive care unit. PATIENTS: Premature infants. INTERVENTION: Probiotic supplementation. MAIN OUTCOME MEASURES: Gut microbiota. RESULTS: A total of 1046 articles were screened, of which 29 were included. There was a large heterogeneity in study design, dose and type of probiotic strains, timepoints of sample collection and analysing techniques. Bifidobacteria and lactobacilli were the most used probiotic strains. The effects of probiotics on alpha diversity were conflicting; however, beta diversity was significantly different between probiotic-supplemented infants and controls in the vast majority of studies. In most studies, probiotic supplementation led to increased relative abundance of the supplemented strains and decreased abundance of genera such as Clostridium, Streptococcus, Klebsiella and Escherichia. CONCLUSIONS: Probiotic supplementation to preterm infants seems to increase the relative abundance of the supplemented strains with a concurrent decrease of potentially pathogenic species. These probiotic-induced microbial alterations may contribute to the decreased risk of health complications such as NEC. Future trials, including omics technologies to analyse both microbiota composition and function linked to health outcomes, are warranted to identify the optimal mixture and dosing of probiotic strains. PROSPERO REGISTRATION NUMBER: CRD42023385204.