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Abstract

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 Lactobacillus brevis can improve blood glucose and body weight of the T2DM mice model and reduce several cancer incidences. However, the therapeutic effect of Lactobacillus brevis in affecting the prognosis of T2DM+HCC remains unknown. In this study, we aim to explore this question via an established T2DM+HCC mice model. We observed a significant alleviation after the probiotic intervention. Lactobacillus brevis 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 Lactobacillus brevis intervention. Furthermore, we found that Lactobacillus brevis delayed disease progression by regulating MMP9 and NOTCH 1 signaling pathways, potentially through gut microflora and BA interaction. This study indicates that Lactobacillus brevis may improve the prognosis of T2DM + HCC, providing novel therapeutic opportunities via targeting intestinal flora for patients with T2DM+HCC.

Keywords: Lactobacillus brevis; MMP9; NOTCH 1 signaling; bile acids; gut microflora; hepatocellular carcinoma; type 2 diabetes.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus brevisDelayed Disease ProgressionBeneficial
Large
Lactobacillus brevisImproved Blood Glucose LevelsBeneficial
Moderate
Lactobacillus brevisImproved Insulin SensitivityBeneficial
Moderate
Lactobacillus brevisReduced Incidence of Colon CancerBeneficial
Moderate
Lactobacillus brevis HA-112Delayed Disease ProgressionBeneficial
Large
Lactobacillus brevis HA-112Improved Blood Glucose LevelsBeneficial
Moderate
Lactobacillus brevis HA-112Improved Insulin SensitivityBeneficial
Moderate
Lactobacillus brevis MAK11L82BImproved Blood Glucose LevelsBeneficial
Moderate
Lactobacillus brevis MAK11L82BImproved Gut MicrofloraBeneficial
Large
Lactobacillus brevis MAK11L82BImproved Insulin SensitivityBeneficial
Moderate
Lactobacillus brevis MAK11L82BReduced Hepatocellular Carcinoma ProgressionBeneficial
Large
Lactobacillus brevis UALbr-02Improved Blood Glucose LevelsBeneficial
Moderate
Lactobacillus brevis UALbr-02Improved Insulin SensitivityBeneficial
Moderate
Lactobacillus brevis UALbr-02Modulated Intestinal Microflora CompositionBeneficial
Moderate
Lactobacillus brevis UALbr-02Reduced Hepatocellular Carcinoma ProgressionBeneficial
Large
Lactobacillus brevis VPro 18Delayed Disease ProgressionBeneficial
Large
Lactobacillus brevis VPro 18Improved Blood Glucose LevelsBeneficial
Moderate
Lactobacillus brevis VPro 18Improved Insulin SensitivityBeneficial
Moderate
Lactobacillus brevis VPro 18Improved Prognosis of Type 2 Diabetes MellitusBeneficial
Moderate
Lactobacillus brevis VPro 18Reduced Incidence of Colon CancerBeneficial
Moderate

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