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

Shujia Chen; Ping Han; Qian Zhang; Peiyan Liu; Jie Liu; Lili Zhao; Lianyi Guo; Jia Li

doi:10.3389/fimmu.2023.1179014

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

Front Immunol. 2023 May 10:14:1179014. doi: 10.3389/fimmu.2023.1179014. eCollection 2023.

Authors

Shujia Chen¹, Ping Han¹, Qian Zhang¹, Peiyan Liu¹, Jie Liu², Lili Zhao², Lianyi Guo³, Jia Li²

Affiliations

¹ Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China.
² Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China.
³ Department of Gastroenterology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bile Acids and Salts
Blood Glucose
Carcinoma, Hepatocellular* / therapy
Diabetes Mellitus, Type 2*
Disease Models, Animal
Gastrointestinal Microbiome*
Levilactobacillus brevis*
Liver Neoplasms* / therapy
Mice

Substances

Bile Acids and Salts
Blood Glucose

Grants and funding

The present work was supported by Natural Science Foundation of Tianjin City (20JCYBJC01150) and Tianjin Health Science and Technology Project (No. TJWJ2021MS034, No. TJWJ2021QN063, and No. TJWJ2021ZD010).