Gut permeability is related to body weight, fatty liver disease and insulin resistance in obese individuals undergoing weight reduction

Background: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. Animal studies showed endotoxemia related to non-alcoholic fatty liver disease (NAFLD), while data in humans are less clear.

Objective: Here we examined markers of gut barrier function in obese individuals with and without NAFLD who underwent a weight reduction program in order to clarify the potential link between barrier function and fatty liver in the context of obesity.

Design: Twenty-seven adult non-diabetic individuals (mean BMI 43.7 ± 5.2 kg/m², 78% with moderate or severe NAFLD) were included. All patients reduced weight by 23.5 kg in average to a mean BMI of 36.4 ± 5.1 kg/m² within 12 months. We assessed barrier functions by the oral lactulose/mannitol (Lac/Man) permeability test and the faecal zonulin test. Insulin resistance was assessed by the HOMA index, liver steatosis by sonography and the fatty liver index.

Results: The median Lac/Man ratio decreased during intervention from 0.048 to 0.016 (P < 0.001). At study start, the Lac/Man ratio was higher in patients with moderate/severe steatosis compared to those with no/mild steatosis (P < 0.001). Patients with the metabolic syndrome had a higher Lac/Man ratio than those without (P = 0.003). The Lac/Man ratio correlated with waist circumference and liver steatosis. Both liver steatosis and Lac/Man ratio correlated with C-reactive protein and insulin resistance. In contrast, zonulin levels did not differ between those with and without NAFLD, and did not change significantly in the course of intervention.

Conclusions: Intestinal permeability is increased in obese patients with NAFLD, compared to obese patients without NAFLD. The increased permeability is associated with abdominal adiposity and insulin resistance, and it normalizes after successful weight reduction.