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Lactobacillus rhamnosus GG attenuates MASLD/MASH progression by modulating gut microbiota and metabolic pathways
Shi-Long Wang1, Si Liang2,3, Si-Yu Li1
1School of Basic Medical Sciences, Hebei University, Baoding, China.
Introduction:
Non-alcoholic fatty liver disease (MASLD) is a common liver condition with a global prevalence of approximately 25%, often associated with overweight, obesity, and abnormalities in glucose and lipid metabolism. Its histological hallmark is hepatic steatosis. Non-alcoholic steatohepatitis (MASH), an advanced form of MASLD, can lead to cirrhosis and liver cancer. Dysbiosis of the gut microbiota plays a significant role in chronic liver diseases, making probiotic treatment a focal point in MASLD research. Studies have shown that Lactobacillus rhamnosus GG (LGG) can improve gut microbiota, reduce hepatic fat accumulation, and lower blood lipid levels in MASLD model mice. However, the role of LGG in the progression from MASLD to MASH remains unclear.
Methods:
In this study, we constructed MASLD and MASH models using a high-fructose, high-fat diet combined with carbon tetrachloride (CCl4) induction to explore the effects of LGG on disease progression. Our findings revealed that in the MASLD model, LGG improved lipid metabolism and inflammatory responses by modulating the gut microbiota (e.g., increasing the abundance of Bacteroidetes) and promoting the production of short-chain fatty acids (SCFAs). Additionally, LGG reduced the expression of genes related to lipogenesis, further alleviating MASLD.
Results:
In the MASH model, LGG primarily exerted its effects by inhibiting the TGF-β/SMAD signaling pathway and reducing the expression of pro-inflammatory factors (e.g., IL-1β, IL-6, TNF-α), thereby mitigating liver fibrosis and inflammation. Furthermore, LGG restored intestinal barrier function, reduced intestinal permeability, and prevented harmful substances like endotoxins from entering the liver, further alleviating hepatic inflammation and fibrosis.
Discussion:
Although LGG shows promise in the treatment of MASLD and MASH, its mechanisms of action and long-term effects require further investigation. Future research should focus on optimizing the types, dosages, and treatment regimens of probiotics, as well as monitoring their long-term impact on gut microbiota balance, to ensure their safety and efficacy in clinical applications.
Insights
Lactobacillus rhamnosus GG (LGG) shows potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, MASH. LGG modulates gut microbiota, improves lipid metabolism, and reduces inflammation in preclinical models.
Area of Science:
- Hepatology and Gastroenterology
- Microbiology and Immunology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 25% of the global population, often linked to obesity and metabolic disorders.
- Non-alcoholic steatohepatitis (MASH), a progressive form of MASLD, can lead to cirrhosis and hepatocellular carcinoma.
- Gut dysbiosis is implicated in MASLD/MASH pathogenesis, highlighting probiotics like Lactobacillus rhamnosus GG (LGG) as potential therapeutic agents.
Purpose of the Study:
- To investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on the progression of MASLD and MASH.
- To elucidate the underlying mechanisms by which LGG influences gut microbiota, lipid metabolism, and inflammatory pathways in liver disease models.
Main Methods:
- Established MASLD and MASH models in mice using a high-fructose, high-fat diet and carbon tetrachloride (CCl4) induction.
- Administered Lactobacillus rhamnosus GG (LGG) to assess its impact on disease progression, gut microbiota composition, and host inflammatory responses.
- Analyzed gene expression, lipid metabolism markers, short-chain fatty acid (SCFA) production, and intestinal barrier integrity.
Main Results:
- In MASLD models, LGG improved lipid metabolism and reduced inflammation by altering gut microbiota (e.g., increasing Bacteroidetes) and boosting SCFA production.
- LGG inhibited lipogenesis-related gene expression, alleviating MASLD.
- In MASH models, LGG suppressed the TGF-β/SMAD pathway, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and restored intestinal barrier function, mitigating liver fibrosis and inflammation.
Conclusions:
- Lactobacillus rhamnosus GG (LGG) demonstrates significant therapeutic potential for both MASLD and MASH by targeting gut dysbiosis, metabolic dysregulation, and inflammatory signaling.
- LGG's ability to restore intestinal barrier integrity is crucial in preventing endotoxin translocation and subsequent liver damage.
- Further research is warranted to optimize probiotic strategies, including dosage and long-term effects, for clinical application in MASLD and MASH.
