Microbiota modulation by dietary oat beta-glucan prevents steatotic liver disease progression
Julius Jaeger, Annette Brandt, Wenfang Gui, Timur Yergaliyev, Angélica Hernández-Arriaga, Mukil Marutha Muthu, Karolina Edlund, Ahmed Elashy, Antonio Molinaro, Diana Möckel, Jan Sarges, Emina Halibasic, Michael Trauner, Florian Kahles, Ulrike Rolle‐Kampczyk, Jan G. Hengstler, Carolin V. Schneider, Twan Lammers, Hanns–Ulrich Marschall, Martin von Bergen�, Amélia Camarinha‐Silva, Ina Bergheim, Christian Trautwein, Kai Markus Schneider
Abstract
Background & AimsMetabolic dysfunction-associated steatotic liver disease (MASLD) - associated changes in gut microbiota are important drivers of disease progression towards fibrosis. Therefore, reversing microbiota 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 fibrosis remains unknown.MethodsWe performed detailed metabolic phenotyping including 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 was modulated using broad-spectrum antibiotic (Abx) treatment.ResultsOat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected.Interestingly, oat beta-glucan dampened MASLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and 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 Abx 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 TLR ligands.ConclusionsOur 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 ImplicationsHere, 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 protecting against bacterial translocation and activation of fibroinflammatory pathways. Together, oat beta-glucan may be a cost-effective and well-tolerated approach in preventing MASLD progression and should be assessed in clinical studies.