Many metabolic disorders are influenced by pathological changes in the intestinal barrier. A new lead study by researchers at the University of Hohenheim reported that gastrointestinal permeability increased in obesity is linked with liver steatosis and can also be a suitable target for therapeutic approach.


Any change in the intestinal barrier usually results in enhanced translocation of commensal intestinal bacteria or bacterial products via the portal vein, to the liver, and finally to the systemic level leading to enhancement of inflammatory cells leading to the onset of gastrointestinal disorders, irritable bowel syndrome, and gastrointestinal infections. Metabolic disorders such as obesity, liver disease, and insulin resistance have also been found to be linked with impairments in the intestinal barrier. A research study was carried by Machado and co-scientists of the Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany for understanding the permeability changes in the intestinal barrier associated with obesity or with associated metabolic diseases or both. They also looked at if these permeability changes were reversible when the weight is reduced. The findings of the study were published in the American Journal of Clinical Nutrition on November 9, 2016.

Researchers carried out a longitudinal study for a period of 1 year on 27 obese individuals (13 men, 14 women) whose age ranged from 18 to 65 years, and no history of chronic gastrointestinal disease and diabetes were registered for a weight-reduction program at the Metabolic Unit of the University of Hohenheim, Stuttgart, Germany.  Gastrointestinal barrier function was established by carrying out two non-invasive tests that include the oral lactulose:mannitol (Lac:Man) permeability test and the fecal zonulin test. In addition, insulin resistance was determined by the homeostatic model assessment index (HOMA) while liver steatosis was determined by sonography and the fatty liver index (FLI) and inflammation by circulating IL6 and endotoxin examinations.

It was interesting to note a significant decrease in intestinal permeability as the Lac:Man ratio dropped to one-third from 0.080 to 0.027 (95% CI: 0.024, 0.034; P , 0.001)  in the 1-year intervention indicating that successful weight reduction can normalize the increased intestinal permeability in the obese. Moreover, zonulin stool concentrations were not influenced by the weight-reduction therapy. Also, the circulating interleukin (IL)-6 concentration also decreased during the intervention process. In the case of steatosis, the Lac:Man ratio was higher in patients with a moderate or severe form of steatosis than those without any steatosis. A multiple-regression analysis revealed both body mass index (BMI) and FLI are related to intestinal permeability which was assessed by the Lac:Man ratio. Therefore, study results indicated the Lac:Man ratio as a valuable marker for determining the intestinal permeability, especially in metabolic disorders.

In short, following unhealthy diet leads to changes in the intestinal barrier, and not only weight reduction but also weight maintenance promotes significant improvements in the intestinal barrier function. Furthermore, a leaky gut barrier is linked to liver steatosis and could be a new target for future therapies.


Written By: Manche Santoshi, PhD

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