Investigating the Effects of Probiotic Treatment on the Gut Microbiome in Preterm Infants

Infants born prematurely have an abnormal set of birth conditions that lead to a sparse,low-diversity population of microbes initially colonizing their guts. Several studies have shown the promise of probiotic treatments to shift the preterm infants’ microbiomes to resemble those of a healthy term infant; however, the functional mechanisms that underlie probiotic’s therapeutic effects remain unknown. The goal of this study is to better understand the role of probiotics in the maturation of the preterm gut microbiomes by using metagenomic data from a longitudinal study of preterm infant gut development where infants sampled from birth to three months. To this end, we constructed metagenome-scale species-resolved computational models of metabolism for each microbiome sample in the study through integrating GEnome-scale Models (GEMs) of metabolism for individual species present in that sample. We further constructed GEMs for all microbial strains that made up the multi-strain probiotic used in the study. We then computationally simulated each microbiota model in the absence and presence of the probiotic strains. Comparing the metabolite production between community models with and without the presence of the probiotic treatment over the sampling time allowed us to identify metabolites that are differentially produced between these two groups and, more importantly, to trace back microbial species that are responsible for their production. Overall, our study is expected to provide unprecedented insight into species and metabolite-level mechanisms of how probiotic treatment accelerates the maturation of the preterm infants’ gut Microbiomes.