Insights from shotgun metagenomics into bacterial species and metabolic pathways associated with NAFLD in obese youth

Abstract Background and Aims NAFLD is the most common form of liver disease and is often the precursor for more serious liver conditions such as NASH and cirrhosis. The gut microbiome has been implicated in the development of NAFLD, but studies have often compared healthy individuals to those with the disease. In this study, we aimed to examine the taxonomic and functional differences between the microbiomes of obese youth with and without NAFLD. Approach and Results Shotgun metagenome sequencing was used to profile the microbial communities of 36 subjects, half of which were diagnosed with NAFLD. Beta diversity analysis showed community-wide differences between the cohorts (p = 0.002). Specific taxonomic differences included the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009) elevated in the NAFLD-positive group and Bacteroides thetaiotamicron (p = 0.0002) elevated in the NAFLD-negative group. At the phylum level, Bacteroidetes (p < 0.0001) was elevated in the NAFLD-negative group. Functionally, branched chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways were elevated in the NAFLD-positive group along with numerous energy utilization pathways including pyruvate fermentation to acetate (p = 0.01318). Conclusions The link between obesity and NAFLD development in younger individuals has rarely been probed, with most studies focusing on adults and comparing healthy individuals with obese, NAFLD-positive individuals. This study supports the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.