Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease

Abstract

Obesity is becoming the new pediatric epidemic. Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, and has become the most common cause of pediatric liver disease. The gut microbiome is the major metabolic organ and determines how calories are processed, serving as a caloric gate, and contributing towards the pathogenesis of NAFLD. The goal of this study is to examine gut microbial profiles in children with NAFLD using phylogenetic, metabolomic, metagenomic, and proteomic approaches. Fecal samples were obtained from obese children with or without NAFLD and healthy lean children. Stool specimens were subjected to 16S rRNA gene microarray, shotgun sequencing, mass spectroscopy for proteomics, and NMR spectroscopy for metabolite analysis. Children with NAFLD had more abundant gamma-proteobacteria and Prevotella and significantly higher levels of short chain fatty acids, and ethanol. This group also had increased genomic and protein abundance for energy production with a reduction in carbohydrate and amino acid metabolism and urea cycle and urea transport systems. The metaproteome and metagenome showed similar findings. The gut microbiome in pediatric NAFLD is distinct from lean healthy children with more alcohol production and pathways allocated to energy metabolism over carbohydrate and amino acid metabolism, which would contribute to development of disease.

Gut microbiota produce alcohol and contribute to NAFLD

“…This is a clear indication that the microbiome of ob/ob mice produces a similar amount of alcohol as the microbiome of lean animals. This observation contrasts with the report that the stools of patients with NAFLD exhibit higher levels of alcohol than that of the healthy subjects 4. In fact, two groups reported that the faecal microbiota in NAFLD has higher representations in alcohol producing microbes 4 5.…”

“…2), including the group led by Bergheim, who first reported elevated serum alcohol in NAFLD 3. Previous studies indicated that the elevated alcohol level in NAFLD is associated with increased representation of alcohol producing bacteria in the gut microbiome 4 5. However, a recent report by Bergheim and her colleagues suggested a very different mechanism for the alcohol spike in NAFLD 6.…”

Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease

“…It therefore appears that levels and subtypes of SCFAs correlate with the severity of fatty liver disease. However, another study reported that some SCFAs, especially formate, acetate and valerate, were less abundant in faecal samples from children with NAFLD 109. These apparent differences might be due to differences in patient age, but could also be related to differences in diet, environmental factors and technical issues.…”

The Gut Microbiota and the Hepatologist: Will Our Bugs Prove to be the Missing Link?

“…In one survey, obese children with NAFLD had a greater abundance of Gammaproteobacteria and Prevotella in the stool microbiome and significantly higher levels of ethanol in the stool metabolome compared to lean healthy children [23] . In another survey, the phylum Proteobacteria , and in particular, the taxa Enterobacteriaceae and Escherichia were increased in abundance in the gut microbiota of children with NASH compared to obese individuals, while obese and NASH children showed greater abundance of Bacteroidetes , predominantly Prevotella , compared to lean children [24] .…”