Responsiveness to 2FL and GOS by infant gut microbiota differs by history of individual 2FL consumption

Background: The microbiota strongly influences human gut homeostasis and health through its metabolites. The metabolic products of the infant microbiota are strongly influenced by human milk or formula feeding. Human milk contains oligosaccharides (HMOS) that are prebiotic, promoting gut colonization by mutualists. Most human milk contains 2-fucosyllactose (2FL) as its principal oligosaccharide, but its abundance varies.Results: A secondary analysis was performed on fecal samples from a randomized, controlled trial (RCT) of 2FL-supplemented or un-supplemented formula to investigate the relationship between dietary exposure to 2FL and the subsequent ability of fecal microbiota to metabolize 2FL and galacto-oligosaccharides (GOS). Microbial metabolic response to these two prebiotics was measured using in vitro anaerobic fermentation with metabolomics read-out, including short-chain fatty acids (SCFA). Microbial diversity was characterized by using whole metagenome sequencing of raw stool. Exposure to 2FL in the trial formula arm primed the growth and metabolism of the microbiota toward increased utilization of 2FL (p=0.005), whereas utilization of GOS, a prebiotic to which the infants had no prior exposure, declined (p=0.18). Individuals with no dietary exposure to prebiotics resulted in their gut microbiota being less responsive to both 2FL (p=0.05) and GOS (p=0.05).Conclusions: The response to 2FL or GOS in baseline fermentation analysis was associated with differences in microbial beta-diversity, suggesting that individual responsiveness to specific prebiotics may be predicted by anaerobic fermentation of their stool samples. Continuous supplementation of prebiotic may prime the gut microbiota to more efficiently utilize this prebiotic.