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

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is often the precursor for more serious liver conditions such as nonalcoholic steatohepatitis and cirrhosis. Although the gut microbiome has been implicated in the development of NAFLD, the strong association of obesity with NAFLD and its effect on microbiome structure has made interpreting study outcomes difficult. In the present study, we examined the taxonomic and functional differences between the microbiomes of youth with obesity and with and without NAFLD. Shotgun metagenome sequencing was performed to profile the microbiomes of 36 subjects, half of whom were diagnosed with NAFLD using abdominal magnetic resonance imaging. Beta diversity analysis showed community‐wide differences between the groups (p = 0.002). Specific taxonomic differences included increased relative abundances of the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009), and a decrease of Bacteroides thetaiotamicron (p = 0.0002), in the NAFLD group as compared with the non‐NAFLD group. At the phylum level, Bacteroidetes (p < 0.0001) was decreased in the NAFLD group. Functionally, branched‐chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways had increased relative abundances in the NAFLD group along with numerous energy use pathways, including pyruvate fermentation to acetate (p = 0.01318). Conclusion: Community‐wide differences were noted based on NAFLD status, and individual bacterial species along with specific metabolic pathways were identified as potential drivers of these differences. The results of the present study support the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.

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).…”

Gut metagenome‐derived signature predicts hepatic decompensation and mortality in NAFLD‐related cirrhosis

“…Gut microbial features have also been shown to be closely associated with liver fibrosis in a population‐based cohort of Hispanics, a patient population with high prevalence of NAFLD 12 . A number of the bacterial taxa that comprise our 13‐species microbial signature of decompensated NAFLD‐related cirrhosis overlap with those taxa previously associated with histologic phenotypes of NAFLD and/or cirrhosis 6,7,13–15 . Veillonellaceae is enriched in cirrhosis and associated with fibrosis severity in non‐obese adults with non‐alcoholic steatohepatitis (NASH), 16,17 and we found Veillonella parvula and Veillonella atypica to be enriched in those with decompensated NAFLD cirrhosis, as compared to those with compensated cirrhosis, in our cohort.…”

“…6 Bacteroides vulgatus has also been associated with differences in metabolic pathways between obese with and without NAFLD. 15 Several taxa were decreased in those with hepatic decompensation, including Alistipes which has been shown to correlate with administration of a glycinerelated compound which facilitated NASH improvement in a murine model. 20 Emerging data support the role of the gut microbiome as a prognostic biomarker in liver diseases other than NAFLD.…”

“…Bacteroides vulgatus , a microbial species in our 13‐species signature, was previously noted to be predominant in NASH‐related advanced fibrosis which suggests progressive dysbiosis occurs even after development of NAFLD‐related cirrhosis 6 . Bacteroides vulgatus has also been associated with differences in metabolic pathways between obese youths with and without NAFLD 15 . Several taxa were decreased in those with hepatic decompensation, including Alistipes which has been shown to correlate with administration of a glycine‐related compound which facilitated NASH improvement in a murine model 20 …”

The Effects of Time-Restricted Eating on Metabolism and Gut Microbiota: A Real-Life Study

“…Furthermore, in the TRE group, we detected statistically significant increases in ASVs, such as Romboutsia, Parasutterella, and Lachnospiraceae, which appear to have contrasting effects on human metabolism. Indeed, Romboutsia, Parasutterella and Lachnospiraceae have been reported to be associated either directly (with a predisposing effect) [43][44][45][46][47] or inversely (with a protective effect) [43,[48][49][50][51] with metabolic abnormalities.…”