Impact of Gut Microbiome Modulating Interventions on Fecal Metabolome of Infants: A Systematic Review and Quality Assessment.

The development of the gut microbiome in infancy is a vulnerable process that may be perturbed by antibiotics or supported by probiotics. Although effects of these "biotics" have been well-studied through DNA sequencing, it remains unclear how the resulting compositional changes affect the microbiome metabolic functions. Additionally, limits in method standardization require careful quality assessment of studies reporting fecal metabolome. We conducted a systematic search in Embase and MEDLINE for studies describing fecal metabolites from term and near-term infants, together with anti-, pre-, or probiotic intervention. The search identified 680 articles, of which 60 were assessed for eligibility and 21 were included. We first developed operational checklists for transparent and reproducible reporting and evaluated the quality of metabolomic methodologies. This analysis supported our aim to summarize changes in the fecal metabolome induced by biotic interventions. Despite a varying quality of metabolomic methodology, we identified similarities in the fecal metabolome profiles in response to specific biotic interventions. Among the most frequently observed metabolites, which were consistently reported to be altered after biotic interventions, were bile acids, aromatic amino acids, and short-chain fatty acids. We conclude with a discussion on appropriate experimental design, controls, and metabolomics reporting to guide future research permitting meta-analyses.