Microbiota modulation by dietary oat beta-glucan prevents steatotic liver disease progression

Background & Aims:Changes in gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) areimportant drivers of disease progression towardsfibrosis. Therefore, reversing microbial alterations could ameliorate MASLDprogression. Oat beta-glucan, a non-digestible polysaccharide, has shown promising therapeutic effects on hyperlipidemiaassociated with MASLD, but its impact on gut microbiota and most importantly MASLD-relatedfibrosis remains unknown. Methods:We performed detailed metabolic phenotyping, including assessments of body composition, glucose tolerance, andlipid metabolism, as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-inducedmodel of MASLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiotawere modulated using broad-spectrum antibiotic treatment. Results:Oat beta-glucan supplementation did not affect WSD-induced body weight gain or glucose intolerance and themetabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened MASLD-related inflammation,which was associated with significantly reduced monocyte-derived macrophage infiltration andfibroinflammatory geneexpression, as well as strongly reducedfibrosis development. Mechanistically, this protective effect was not mediated bychanges in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon broad-spectrumantibiotic treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in anexpansion of protective taxa, includingRuminococcus, andLactobacillusfollowed by reduced translocation of Toll-like receptorligands. Conclusions:Ourfindings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation andfibrosis development in diet-induced MASLD. These results, along with its favorable dietary profile, suggest that it may be acost-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 andfibrosis developmentin a mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD). Beta-glucan significantly reducedinflammation andfibrosis in the liver, which was associated with favorable shifts in gut microbiota that protected againstbacterial translocation and activation offibroinflammatory pathways. Together, oat beta-glucan may be a cost-effective andwell-tolerated approach to prevent MASLD progression and should be assessed in clinical studies .(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is anopen access article under the CC BY-NC-ND license