title: Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction.
abstract: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier.
  
  
  
  We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function.
  
  
  
  Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m2): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI).
  
  
  
  The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio.
  
  
  
  Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525.
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Damms-Machado
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Louis
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Schnitzer
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Volynets
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rings
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Basrai
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany bischoff.stephan@uni-hohenheim.de.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D002772:Cholera Toxin / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006242:Haptoglobins; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D007408:Intestinal Absorption; D007422:Intestines / Q000503:physiopathology*; D007792:Lactulose / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D010539:Permeability; D011498:Protein Precursors; D055105:Waist Circumference; D015431:Weight Loss / Q000502:physiology*; D055815:Young Adult
chemical_list: D006242:Haptoglobins; D015850:Interleukin-6; D011498:Protein Precursors; C408043:zonulin; D008353:Mannitol; D007792:Lactulose; D002772:Cholera Toxin
keywords: gut barrier; insulin resistance; intestinal permeability; liver steatosis; obesity