BACKGROUND: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE: 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. DESIGN: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE: 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 obesepatients with or without liver steatosis differ in this function. DESIGN: 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). RESULTS: 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. CONCLUSIONS: Intestinal permeability is increased in obesepatients with steatosis compared with obesepatients 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: Michael W Rohr; Chandrakala A Narasimhulu; Trina A Rudeski-Rohr; Sampath Parthasarathy Journal: Adv Nutr Date: 2020-01-01 Impact factor: 8.701
Authors: Martin O Weickert; John G Hattersley; Ioannis Kyrou; Ayman M Arafat; Natalia Rudovich; Michael Roden; Peter Nowotny; Christian von Loeffelholz; Silke Matysik; Gerd Schmitz; Andreas F H Pfeiffer Journal: Nutr Diabetes Date: 2018-03-07 Impact factor: 5.097
Authors: Lucas Scheffler; Alyce Crane; Henrike Heyne; Anke Tönjes; Dorit Schleinitz; Christian H Ihling; Michael Stumvoll; Rachel Freire; Maria Fiorentino; Alessio Fasano; Peter Kovacs; John T Heiker Journal: Front Endocrinol (Lausanne) Date: 2018-02-05 Impact factor: 5.555