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.

Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease

“…Thus, this genus might be an indicator of hepatic steatosis. Our finding on the lower abundance of Bacteroides agrees with a study by Testerman et al in NAFLD patients ( 13 ), while opposite findings also exist ( 15 ). However, contrary to our results, Testerman and coworkers found that two GM pathways of histidine degradation were decreased in NAFLD patients ( 13 ).…”

“…Our finding on the lower abundance of Bacteroides agrees with a study by Testerman et al in NAFLD patients ( 13 ), while opposite findings also exist ( 15 ). However, contrary to our results, Testerman and coworkers found that two GM pathways of histidine degradation were decreased in NAFLD patients ( 13 ). In contrast, elevated urinary methylhistidine has been described in NAFLD patients ( 39 ).…”

“…We have found that in humans high hepatic fat content is linked to lower abundance of Faecalibacterium prausnitzii ( 10 ), and further, in a mouse model we have been able to ameliorate NAFLD by administering F. prausnitzii ( 11 ). One previous study reported that NAFLD patients have lower abundance of Bacteroidetes ( 12 ), and another lower abundance of Bacteroides ( 13 ). Contrarily, others have shown higher abundance of Bacteroides in NAFLD ( 14 , 15 ).…”

Meta-analysis reveals obesity associated gut microbial alteration patterns and reproducible contributors of functional shift

“…Altogether, at FDR < 0.1 and effect size cut off ±0.2, we identified a set of 17 species reproducible across the datasets majority of which are control-enriched and previously associated with healthy metabolic status and BMI (Figure 3B and Table S4.1) (Liu et al, 2017;Testerman et al, 2021;Verdam et al, 2013;Zhernakova et al, 2016). On the other hand , the obese-enriched taxa were also linked to impaired host energy metabolism or high BMI (Liu et al, 2017).…”