Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Annette Brandt
Department of Nutritional Sciences, University of Vienna, Vienna, Austria
Wenfang Gui
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Timur Yergaliyev
Department Microbial Ecology of Livestock at the Institute of Animal Science, University of Hohenheim, Stuttgart, Germany
Angélica Hernández-Arriaga
Department Microbial Ecology of Livestock at the Institute of Animal Science, University of Hohenheim, Stuttgart, Germany
Mukil Marutha Muthu
Department Microbial Ecology of Livestock at the Institute of Animal Science, University of Hohenheim, Stuttgart, Germany
Karolina Edlund
Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany
Ahmed Elashy
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Antonio Molinaro
Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden; Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Diana Möckel
Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University, Aachen, Germany
Jan Sarges
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Emina Halibasic
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
Michael Trauner
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
Florian Kahles
Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany
Ulrike Rolle-Kampczyk
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany
Jan Hengstler
Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany
Carolin Victoria Schneider
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Twan Lammers
Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Hanns-Ulrich Marschall
Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden
Martin von Bergen
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany
Amélia Camarinha-Silva
Department Microbial Ecology of Livestock at the Institute of Animal Science, University of Hohenheim, Stuttgart, Germany
Ina Bergheim
Department of Nutritional Sciences, University of Vienna, Vienna, Austria
Christian Trautwein
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Kai Markus Schneider
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Corresponding author. Address: Department of Medicine III, University Hospital, RWTH Aachen, Pauwelsstraße, 30, Aachen 52074, Germany. Tel.: +49-241-80-8037727, fax: +49-241-80-37727.
Background & Aims: Changes in gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) are important drivers of disease progression towards fibrosis. Therefore, reversing microbial alterations could ameliorate MASLD progression. Oat beta-glucan, a non-digestible polysaccharide, has shown promising therapeutic effects on hyperlipidemia associated with MASLD, but its impact on gut microbiota and most importantly MASLD-related fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping, including assessments of body composition, glucose tolerance, and lipid metabolism, as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of MASLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota were modulated using broad-spectrum antibiotic treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain or glucose intolerance and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened MASLD-related inflammation, which was associated with significantly reduced monocyte-derived macrophage infiltration and fibroinflammatory gene expression, as well as strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon broad-spectrum antibiotic treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of Toll-like receptor ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced MASLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing MASLD progression and should be assessed in clinical studies. Impact and Implications: Herein, we investigated the effect of oat beta-glucan on the gut-liver axis and fibrosis development in a mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD). Beta-glucan significantly reduced inflammation and fibrosis in the liver, which was associated with favorable shifts in gut microbiota that protected against bacterial translocation and activation of fibroinflammatory pathways. Together, oat beta-glucan may be a cost-effective and well-tolerated approach to prevent MASLD progression and should be assessed in clinical studies.
