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Microbiota modulation by dietary oat beta-glucan prevents steatotic liver disease progression
Julius W Jaeger1, Annette Brandt2, Wenfang Gui1
1Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
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.
Insights
Oat beta-glucan supplementation reduced liver inflammation and fibrosis in a mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD). This effect was linked to beneficial gut microbiota changes, suggesting a potential dietary approach for MASLD progression.
Area of Science:
- Gastroenterology and Hepatology
- Microbiology
- Nutrition Science
Background:
- Gut microbiota alterations are key drivers of metabolic dysfunction-associated steatotic liver disease (MASLD) progression.
- Oat beta-glucan's effects on MASLD-related fibrosis and gut microbiota remain largely unknown.
- Understanding these interactions is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of oat beta-glucan on the gut-liver axis and fibrosis in a diet-induced MASLD mouse model.
- To determine if oat beta-glucan can ameliorate MASLD progression and associated gut dysbiosis.
- To elucidate the mechanisms underlying oat beta-glucan's effects on liver inflammation and fibrosis.
Main Methods:
- Induction of MASLD in mice using a western-style diet (WSD).
- Administration of oat beta-glucan and assessment of metabolic parameters, liver histology, and gut microbiota.
- Modulation of gut microbiota using broad-spectrum antibiotics to test dependency.
Main Results:
- Oat beta-glucan supplementation did not alter body weight or glucose intolerance but significantly reduced liver inflammation and fibrosis.
- The protective effects were dependent on gut microbiota and associated with favorable shifts in microbial composition, including expansion of *Ruminococcus* and *Lactobacillus*.
- Reduced bacterial translocation and Toll-like receptor ligand signaling were observed.
Conclusions:
- Oat beta-glucan acts as an effective food supplement in dampening inflammation and fibrosis in diet-induced MASLD.
- The mechanism involves beneficial modulation of the gut microbiota, reducing bacterial translocation.
- Oat beta-glucan presents a potential cost-effective and well-tolerated strategy for preventing MASLD progression, warranting clinical investigation.
