Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.

Shanthi G Parkar, Christopher E Mason, Raja Dhir, Gregor Reid, Peter A Bron, Marco Pane, Gabriel A Al-Ghalith, Ece Kartal, Noah Voreades, Joseph F Petrosino, Gerard Smits, Jared Boetes, Emeran A Mayer, Bruno P Chumpitazi, Alessio Fasano, James Versalovic, Braden T Tierney

Journal: Pediatric research 2023;93(7):2005-2013

PMID: 36319696

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Plain Language Summary

The composition of the human gut microbiome has been identified as playing a role in regulating bowel movements in children. This includes functional constipation, which is characterised by infrequent bowel movements and associated phenotypes such as stool consistency, pain when defecating and bloating. The aim of this study was to determine the impact of a nine-strain (eight species) synbiotic (a prebiotic and defined microbial consortium) formulation (with the prebiotic comprising mixed-chain length oligosaccharides) on ameliorating constipation. This study was a multicentre, randomised, double-blind, and placebo-controlled with two parallel arms. Ninety-one healthy male/female subjects were recruited and randomly assigned to one of the two arms; treatment or placebo group. Results showed that: - compared to placebo, synbiotic use increased weekly bowel movements (WBMs) in constipated children. - there was an increased abundance of the administered probiotic species (bifidobacteria) in the treatment arm. - baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention. Authors conclude that a synbiotic formulation may increase weekly WBMs in children who have low-frequency WBMs.

Abstract

BACKGROUND

Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.

METHODS

Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo.

RESULTS

Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074).

CONCLUSIONS

These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.

IMPACT

Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.

Address: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA.; Seed Health, Venice, CA, USA.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.; Department of Pathology, Texas Children's Hospital, Houston, TX, USA.; Mucosal Immunology and Biology Research Center, Center for Celiac Research and Treatment and Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA.; Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Neurogastroenterology and Motility Program, Texas Children's Hospital, Houston, TX, USA.; Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.; G Oppenheimer Center for Neurobiology of Stress and Resilience, Los Angeles, CA, USA.; Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg, Germany.; Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, ON, Canada.; Departments of Microbiology and Immunology and Surgery, Western University, London, ON, Canada.; Seed Health, Venice, CA, USA. [email protected].; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA. [email protected].

DOI: 10.1038/s41390-022-02289-0