Human intestinal microbiota and intestinal permeability in relation to non-alcoholic fatty liver disease and short-term overfeeding

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Title: Human intestinal microbiota and intestinal permeability in relation to non-alcoholic fatty liver disease and short-term overfeeding
Author: Jian, Ching
Other contributor: Helsingin yliopisto, Maatalous-metsätieteellinen tiedekunta, Elintarvike- ja ympäristötieteiden laitos
University of Helsinki, Faculty of Agriculture and Forestry, Department of Food and Environmental Sciences
Helsingfors universitet, Agrikultur- och forstvetenskapliga fakulteten, Institutionen för livsmedels- och miljövetenskaper
Publisher: Helsingfors universitet
Date: 2016
Language: eng
Thesis level: master's thesis
Discipline: Biotekniikka (EYT)
Biotechnology (EYT)
Bioteknik (EYT)
Abstract: Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease in the western world. The human intestinal microbiota possesses enormous metabolic and immunomodulatory capabilities, and together with increased intestinal permeability, changes in the microbiota have been linked to the development of NAFLD. However, human studies so far have yielded contradictory findings regarding the compositional microbiota changes and provided little mechanistic understanding due to the predominance of cross-sectional studies. The aim of this study was to study human intestinal microbiota and gut permeability in NAFLD. Real-time PCR was employed to quantify the key intestinal bacterial groups in overweight or obese subjects with (n = 12) and without (n = 19) NAFLD, and in response to hypercaloric overfeeding, where participants were provided with three compositionally distinct diets to temporarily increase liver fat. In addition to the comparative analysis, the microbiota results were correlated to serum markers of intestinal permeability and metabolic endotoxemia, as well as clinical parameters related to NAFLD. The results show that host lipid metabolism and the gut microbiota, specifically Bacteroidetes and Clostridium cluster XIVa, are firmly intercorrelated. Bacteroidetes were found to be less abundant in subjects with NAFLD and correlate negatively with liver fat and serum triglycerides at baseline. Clostridium cluster XIVa, a dominant Firmicute group, was positively associated with serum triglycerides and pro-inflammatory markers but negatively with intestinal permeability. The relative abundance of Bacteroidetes as well as the markers of metabolic endotoxemia changed significantly in response to overfeeding, while no diet-induced systematic effects were found in Clostridium cluster XIVa, total bacteria, Escherichia coli group, Bifidobacterium or gut permeability. Our results based on a targeted microbiota analysis suggest that the role of the intestinal microbiota and gut permeability on triggering metabolic disarrangement and NAFLD in humans is inferior to other stimuli, such as diet.
Subject: NAFLD
intestinal microbiota
intestinal permeability

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