Lactobacillus brevis alleviates the progress of hepatocellular carcinoma and type 2 diabetes in mice model via interplay of gut microflora, bile acid and NOTCH 1 signaling.

Frontiers in immunology(2023)

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摘要
Type 2 diabetes (T2DM) clinically exhibits a higher incidence of hepatocellular carcinoma (HCC), contributing to a lousy prognosis in patients harboring both diseases. Microflora-based therapy draws attention with low side effects. Accumulating evidence shows that can improve blood glucose and body weight of the T2DM mice model and reduce several cancer incidences. However, the therapeutic effect of in affecting the prognosis of T2DM+HCC remains unknown. In this study, we aim to explore this question an established T2DM+HCC mice model. We observed a significant alleviation after the probiotic intervention. improves blood glucose and insulin resistance and ameliorates Mechanically. Combined with a multi-omics approach including 16SrDNA, GC-MS, and RNA-seq, we identified distinct intestinal microflora composition and metabolites after intervention. Furthermore, we found that delayed disease progression by regulating MMP9 and NOTCH 1 signaling pathways, potentially through gut microflora and BA interaction. This study indicates that may improve the prognosis of T2DM + HCC, providing novel therapeutic opportunities targeting intestinal flora for patients with T2DM+HCC.
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关键词
type 2 diabetes, hepatocellular carcinoma, Lactobacillus brevis, gut microflora, bile acids, NOTCH 1 signaling, MMP9
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