Endotoxemia unrequired in the pathogenesis of pediatric nonalcoholic steatohepatitis

Abstract

Background and aim: Nonalcoholic steatohepatitis (NASH), the severe form of nonalcoholic fatty liver disease, is a serious liver complication associated with obesity. Several studies suggest that endotoxemia is associated with nonalcoholic fatty liver disease and NASH. We aimed to study the correlation of gut microbiome composition and the incidence of endotoxemia in obese patients and NASH patients in comparison with normal controls.

Methods: The abundance of Gram-negative bacteria in the gut microbiomes of normal controls, obese patients with normal liver, and biopsy-proven NASH patients were assessed using 16S rRNA pyrosequencing data. Serum endotoxin was determined by endpoint limulus amebocyte lysate assay.

Results: Higher abundance of Gram-negative bacteria in gut microbiome was observed in obese and NASH patients in comparison with normal controls, but no difference was detected between obese and NASH patients. Serum endotoxin is higher in the NASH group than the normal controls. In addition, the obese and NASH patients had a higher incidence of endotoxemia compared with normal controls. However, Spearman's test found no correlation between the abundance of Gram-negative bacteria and serum endotoxin levels. The majority of the NASH patients and the obese patients had low serum endotoxin level. Among NASH patients, serum endotoxin is not correlated with disease severity.

Conclusions: Our data suggest that the gut microbiome composition does not contribute to the incidence of endotoxemia in NASH, and endotoxemia is not required in the pathogenesis of NASH. Our observations highlight the current concept that multiple factors contribute to the development of NASH.

Keywords: Gram-negative; endotoxin; lipopolysaccharide; microbiome.