Genome Scale Metabolic Analysis of the Lactobacillus Genus with a Focus on Probiotic Strains

The Lactobacillus genus has, primarily, dominated the probiotic industry with a great deal of success in conferring health benefit as shown in a variety of rigorous clinical trials. In this study, we generate over 200 genome-scale metabolic reconstructions from a broad array of Lactobacillus species, including many of the currently sequenced species that are typically found in marketed probiotics, resident strains from human isolation sites, and fermented foods. We have conducted a strain level comparison of the reactomes for each genome, demonstrating that the metabolic reactome contributes to clustering of the genomes based on human health related isolation sites, including the gut, oral cavity, and vagina. Strains resident to the vaginal microbiota cluster separately from strains resident to the gastrointestinal tract, while there is a large overlap in metabolic potential between gut and oral residents. A random forest analysis was used to identify reactions specific to resident strains to the gastrointestinal tract when compared to other lactobacillus strains. Carbon and amino acid source utilization was predicted using the generated metabolic reconstructions, our data indicate that there is a great deal of variation among Lactobacillus strains with some correlation to isolation site. We present a phylogenetic analysis based on metabolic capabilities, demonstrating the similarities among Lactobacillus strains indicating which groups are most likely to compete in a microbial community. The metabolic reconstructions were generated using ModelSEEDs universal format, the PATRIC database, Mackinac, CobraPy, and Probannopy. This study provides a public resource of systematically generated genome scale metabolic reconstructions for a wide range of Lactobacillus strains for further curation and analysis of probiotics relevant to human oral, gut, and vaginal health. Additionally, this work lays the ground work for personalize design, selection, and delivery of Lactobacillus based probiotics.