The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis

Background - Small intestinal bacterial overgrowth may contribute to the development of non-alcoholic steatohepatitis, perhaps by increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products. Aims - To investigate the prevalence of small intestinal bacterial overgrowth, increased intestinal permeability, elevated endotoxin, and tumour necrosis factor α (TNF-α) levels in patients with non-alcoholic steatohepatitis and in control subjects. Patients and methods - Twenty two patients with non-alcoholic steatohepatitis and 23 control subjects were studied. Small intestinal bacterial overgrowth was assessed by a combined ¹⁴C-D-xylose and lactulose breath test. Intestinal permeability was assessed by a dual lactuloserhamnose sugar test. Serum endotoxin levels were determined using the limulus amoebocyte lysate assay and TNF-α levels using an ELISA. Results - Small intestinal bacterial overgrowth was present in 50% of patients with non-alcoholic steatosis and 22% of control subjects (p=0.048). Mean TNF-α levels in non-alcoholic steatohepatitis patients and control subjects were 14.2 and 7.5 pg/ml, respectively (p=0.001). Intestinal permeability and serum endotoxin levels were similar in the two groups. Conclusions - Patients with non-alcoholic steatohepatitis have a higher prevalence of small intestinal bacterial overgrowth, as assessed by the ¹⁴C-D-xylose-lactulose breath test, and higher TNF-α levels in comparison with control subjects. This is not accompanied by increased intestinal permeability or elevated endotoxin levels.