Di-Mi-Liv

Dietary modulation of intestinal microbiota as trigger of liver health: role of bile acids

Project description

Genetic predisposition and general overnutrition are discussed as key factors in the development of non-alcoholic fatty liver disease (NAFLD); however, alterations of intestinal microbiota composition and associated impairments of intestinal barrier function are thought to be critical in the onset and progression of NAFLD. Also studies suggest a pivotal role of bile acids and microbial bile acid metabolism as mediators of gut-liver-crosstalk, subsequently affecting NAFLD initiation and progression. Soluble fibers like oat β-glucans bind bile acids and have been proposed to modulate intestinal microbiota composition, thereby affecting metabolic parameters and liver health. Based on this background, the main aim of the transnational Di-Mi-Liv project was to reveal a causal relationship between specific diet-responsive microbial taxa and alterations of the bile acid pool as risk factor for initiation and progression of metabolic liver diseases. Herein, the effects of the soluble fiber oat β-glucan were assessed. Key findings achieved within the project include that in patients with NAFLD fiber intake is ~12g/d lower than that recommended by the nutrition societies. Also, with the help of the two high-fiber flake mixes employed in the intervention study, the daily fiber intake could be significantly increased almost to the level of the recommendations during the intervention phase without significantly changing the general dietary pattern. In the groups consuming insoluble fibers, this was associated with a marked decrease of transaminase activity and concentration of TLR ligands in blood while fecal microbiota and bile acid composition was widely unaffected. In patients, the intake of oat β-glucan rich flakes had limited effects on liver parameters and fecal microbiota composition. In contrast, in mouse studies employing models of early and late stages of NAFLD a diet enriched with oat β-glucan (~30% of total fiber intake) markedly protected mice from the development of early stages of NAFLD. The protection from liver disease progression and liver fibrosis seemed to be dependent on the action of oat β-glucan on intestinal microbiota and intestinal FXR-activation.

In summary, the results of our project suggest that oat β-glucan may have some protective effects on the development of metabolic diseases. However, in settings of a pre-existing NAFLD, it seems that an increase in the intake of other fibers like insoluble spelt bran might be more beneficial.

Consortium

Partner Organization Partner Country
University Clinic RWTH Aachen Germany
Medical University of Vienna Austria
University of Gothenburg Sweden
University of Hohenheim Germany

 

Highlights

Lifestyle interventions, including an increase in physical activity and change of diet are still the main therapeutic interventions in the treatment of NAFLD; however, they are often afflicted with low compliance and adherence. Within the Di-Mi-Liv project, five research groups from three different European countries assessed the role of dietary fibers in the development and therapy of NAFLD. Key findings include that the daily fiber intake of patients with NAFLD was lower than recommended. Furthermore, results of the study also suggest that different fibers may impact human health differently and that the effects may be related to the overall health status of the individual.  

Products

Title: Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis
Author: Lijun Liao, Kai Markus Schneider*, Eric J C Galvez, Mick Frissen, Hanns-Ulrich Marschall*, Huan Su, Maximilian Hatting, Annika Wahlström, Johannes Haybaeck, Philip Puchas, Antje Mohs, Jin Peng, Ina Bergheim*, Anika Nier, Julia Hennings, Johanna Reißing, Henning W Zimmermann, Thomas Longerich, Till Strowig, Christian Liedtke, Francisco J Cubero, Christian Trautwein*
Link: http://dx.doi.org/10.1136/gutjnl-2018-316670
Title: Intestinal microbiota protects against MCD diet induced steatohepatitis
Author: Kai Markus Schneider*, Antje Mohs, Konrad Kilic, Lena Susanna Candels, Carsten Elfers, Eveline Bennek, Lukas Ben Schneider, Felix Heymann, Nikolaus Gassler, John Penders, Christian Trautwein*
Link: https://doi.org/10.3390/ijms20020308
Title: Effects of different standard and special diets on cognition and brain mitochondrial function in mice
Author: Martina Reutzel, Rekha Grewal, Carsten Esselun, Sebastian Friedrich Petry, Thomas Linn, Annette Brandt, Ina Bergheim*, Gunter P Eckert
Link: https://doi.org/10.1080/1028415x.2021.1906392
Title: The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging
Author: Eva Untersmayr, Annette Brandt, Larissa Koidl, Ina Bergheim*
Link: https://doi.org/10.3390/nu14050949
Title: Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment
Author: Kai Markus Schneider*, Antje Mohs, Wenfang Gui, Eric J C Galvez, Lena Susanna Candels, Lisa Hoenicke, Uthayakumar Muthukumarasamy, Christian H Holland, Carsten Elfers, Konrad Kilic, Carolin Victoria Schneider, Robert Schierwagen, Pavel Strnad , Theresa H Wirtz, Hanns-Ulrich Marschall*, Eicke Latz, Benjamin Lelouvier, Julio Saez-Rodriguez, Willem de Vos, Till Strowig, Jonel Trebicka ,Christian Trautwein*
Link: https://doi.org/10.1038/s41467-022-31312-5
Title: Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signaling
Author: Schneider KM*, Candels LS, Hov JR, Myllys M, Hassan R, Schneider CV, Wahlström A, Mohs A, Zühlke S, Liao L, Elfers C, Kilic K, Henricsson M, Molinaro A, Hatting M, Zaza A, Drasdo D, Frissen M, Devlin AS, Gálvez EJC, Strowig T, Karlsen TH, Hengstler JG, Marschall HU*, Ghallab A, Trautwein C.*
Link: https://doi.org/10.1038/s42255-021-00452-1
Title: Intestinal Dysbiosis Amlifies Acetaminophen Induced Acute Liver Injury
Author: Kai Markus Schneider*, Carsten Elfers, Ahmed Ghallab, Carolin Victoria Schneider, Eric J.C. Galvez, Antje Mohs, Wenfang Gui, Lena Susanna Candels, Theresa Hildegard Wirtz, Sebastian Zuehlke, Michael Spiteller, Maiju Myllys, Alain Roulet, Amirouche Ouzerdine, Benjamin Lelouvier, Konrad Kilic, Lijun Liao, Anika Nier*, Eicke Latz, Ina Bergheim*, Christoph A. Thaiss, Jan G. Hengstler, Till Strowig, and Christian Trautwein*
Link: https://doi.org/10.1016/j.jcmgh.2020.11.002
Title: Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis
Author: Lijun Liao, Kai Markus Schneider*,Eric J C Galvez, Mick Frissen, Hanns-Ulrich Marschall*, Huan Su, Maximilian Hatting, Annika Wahlström, Johannes Haybaeck, Philip Puchas, Antje Mohs, Jin Peng, Ina Bergheim*, Anika Nier, Julia Hennings, Johanna Reißing, Henning W Zimmermann, Thomas Longerich, Till Strowig, Christian Liedtke, Francisco J Cubero, Christian Trautwein*
Link: https://doi.org/10.1136/gutjnl-2018-316670

 

Target group Authors Means of communication Hyperlink Pdf
International Hepatology Community Ina Bergheim, Hanns-Ulrich Marschall, Kai Markus Schneider, Christian Trautwein, Talk: : “Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis”, EASL ILC, Vienna 2019 Oral Presentation    

Features

Project number:
Di-Mi-Liv
Duration: 100%
Duration: 100 %
2018
2022
Project lead and secretary:
Ina Bergheim