Universität zu Köln

Lang, Sonja, Martin, Anna, Zhang, Xinlian, Farowski, Fedja, Wisplinghoff, Hilmar, J. G. T. Vehreschild, Maria, Krawczyk, Marcin ORCID: 0000-0002-0113-0777, Nowag, Angela, Kretzschmar, Anne, Scholz, Claus, Kasper, Philipp, Roderburg, Christoph, Mohr, Raphael, Lammert, Frank, Tacke, Frank, Schnabl, Bernd, Goeser, Tobias, Steffen, Hans-Michael and Demir, Muenevver (2021). Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease. Liver Int., 41 (7). S. 1576 - 1592. HOBOKEN: WILEY. ISSN 1478-3231

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Abstract

Background and 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 were 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/m(2): 1.23, 95% CI 1.10-1.37, P < .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 = .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 cofactors 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 underscore the multifactorial pathogenesis of NAFLD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lang, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Xinlian UNSPECIFIED UNSPECIFIED UNSPECIFIED Farowski, Fedja UNSPECIFIED UNSPECIFIED UNSPECIFIED Wisplinghoff, Hilmar UNSPECIFIED UNSPECIFIED UNSPECIFIED J. G. T. Vehreschild, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Krawczyk, Marcin UNSPECIFIED orcid.org/0000-0002-0113-0777 UNSPECIFIED Nowag, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Kretzschmar, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kasper, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Roderburg, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohr, Raphael UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammert, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Tacke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnabl, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Goeser, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Steffen, Hans-Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Demir, Muenevver UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-603278
DOI:	10.1111/liv.14899
Journal or Publication Title:	Liver Int.
Volume:	41
Number:	7
Page Range:	S. 1576 - 1592
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1478-3231
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REPORTED ENERGY-INTAKE; FIBROSIS; ACTIVATION; DYSBIOSIS; SEVERITY; RS738409; OUTCOMES; NAFLD; RISK Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60327