A randomized controlled study protocol of the TOBBI trial: the effect of a 6 weeks intervention with synbiotics on the recovery speed of the gut microbiota after antibiotic treatment in Dutch toddlers.

Background: Antibiotic-induced disruption of the gut microbiome in the first 1000 days of life is linked to an increased risk of the development of immunological, metabolic, and neurobehavioral childhood-onset conditions. Supporting the recovery of the gut microbial community after it has been perturbed by antibiotics might be a promising strategy to reduce these risks. In this clinical study, the effect of a 6 weeks supplementation with synbiotics (Bifidobacterium breve M-16 V, short chain galacto-oligosaccharides and long chain fructo-oligosaccharides) after antibiotic treatment on the recovery speed of the gut microbiota of toddlers will be studied.

Methods/design: A cohort of 126 Dutch toddlers aged 12 to 36 months old, who receive an amoxicillin or amoxicillin/clavulanic acid treatment, will be followed for 12 weeks. Participants will be randomized into an intervention group, who will consume the study product over a 6 weeks period starting at the last day of the antibiotic treatment or into a control group that will continue their usual eating pattern. Stool samples and their characteristics will be collected weekly by both groups. Stool samples will be analyzed for total microbiota and Bifidobacterium spp.. The differences in the proportion of Bifidobacterium out of total gut microbiota, composition of species belonging to Bifidobacterium, and beta diversity overtime will be compared between the two groups to study the effect of the intervention on the gut microbiota after perturbation. Furthermore, the effect of the treatment will also be studied in terms of the gut microbiota metabolic activity and stool characteristics. Additionally, food intake will be recorded to investigate whether diet, especially dietary fibers, may influence the gut microbiota as well. The findings may highlight a potential intervention strategy to support the recovery of the gut community after it has been perturbed by antibiotics in early life.

Trial Registration: The TOBBI trial was approved by the board of Medical Ethics Review Committee NedMec in June 2022 and registered at  https://www.onderzoekmetmensen.nl/en/trial/20358 under the code NL75975.081.20, and at the World Health Organization at https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON20358 under NTR-new: NL8996.