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Abstract Details
Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease
Sonja Lang12, Anna Martin1, Xinlian Zhang3, Fedja Farowski456, Hilmar Wisplinghoff789, Maria J G T Vehreschild456, Marcin Krawczyk1011, Angela Nowag79, Anne Kretzschmar7, Claus Scholz7, Philipp Kasper1, Christoph Roderburg12, Raphael Mohr13, Frank Lammert1014, Frank Tacke13, Bernd Schnabl215, Tobias Goeser1, Hans-Michael Steffen1, Münevver Demir13
Author information
1University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany.
2Department of Medicine, University of California San Diego, La Jolla, CA, USA.
3Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
4University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
5German Centre for Infection Research (DZIF), partner site Bonn/Cologne.
6Department of Internal Medicine, Infectious Diseases, Goethe University, Frankfurt, Frankfurt am Main, Germany.
7Wisplinghoff Laboratories, Cologne, Germany.
8Institute for Virology and Medical Microbiology, University Witten/Herdecke, Witten, Germany.
9University of Cologne, Faculty of Medicine, Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
10Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
11Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
12Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
13Department of Hepatology and Gastroenterology, Campus Virchow Clinic and Campus Charité Mitte, Charité University Medicine, Berlin, Germany.
14Hannover Medical School (MHH), Hannover, Germany.
15Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
Abstract
Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.
Methods: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants, and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed.
Results: Complete data was available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P<0.001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P=0.007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger, were associated with the degree of inflammation, ballooning, and stages of fibrosis, even after taking other co-factors into account.
Conclusions: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscores the multifactorial pathogenesis of NAFLD.