Metagenome-Scale Metabolic Network Suggests Folate Produced by Bifidobacterium longum Might Contribute to...

Gut-microbiota-targeted nutrition intervention has achieved success in the management of obesity, but its underlying mechanism still needs extended exploration. An obese Prader-Willi syndrome boy lost 25.8 kg after receiving a high-fiber dietary intervention for 105 days. The fecal microbiome sequencing data taken from the boy on intervention days 0, 15, 30, 45, 60, 75, and 105, along with clinical indexes, were used to construct a metagenome-scale metabolic network. Firstly, the abundances of the microbial strains were obtained by mapping the sequencing reads onto the assembly of gut organisms through use of reconstruction and analysis (AGORA) genomes. The nutritional components of the diet were obtained through the Virtual Metabolic Human database. Then, a community model was simulated using the Microbiome Modeling Toolbox. Finally, the significant Spearman correlations among the metabolites and the clinical indexes were screened and the strains that were producing these metabolites were identified. The high-fiber diet reduced the overall amount of metabolite secretions, but the secretions of folic acid derivatives by Bifidobacterium longum strains were increased and were significantly relevant to the observed weight loss. Reduced metabolites might also have directly contributed to the weight loss or indirectly contribute by enhancing leptin and decreasing adiponectin. Metagenome-scale metabolic network technology provides a cost-efficient solution for screening the functional microbial strains and metabolic pathways that are responding to nutrition therapy.