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

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.

Physiochemical characterization and ameliorative effect of rice resistant starch modified by heat-stable α-amylase and glucoamylase on the gut microbial community in T2DM mice

“…Lactobacillus , a probiotic, has been confirmed to have the function of improving the intestinal mucosal barrier, reducing inflammation and maintaining the balance of blood sugar. 66 The result showed that the relative abundance of Lactobacillus in T2DM mice was decreased. However, it could be regulated by ingesting RRS, and the abundance gradually increases with an increase in the RRS dose.…”

Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study

“…It would be interesting to recommend a larger study with simultaneous measurements of HbA1c, succinate and other serum parameters to confirm this observation. This may open up prospects for using specific succinate consuming bacteria that are beneficial to host health or to administer succinate-consuming probiotics and promote their growth through high fibre dietary intervention, which is expected to lead to the uptake of excessive succinate and provide new avenues for treating related diseases ( Muhammad et al, 2023 ; Sharma, Bhardwaj & Singh, 2016 ; Bernier et al, 2021 ; Chen et al, 2023 ).…”

Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: A prospective, open label, controlled, randomized, comparative, proof of concept study

“…The observation of this study also indicates the potential of Bifidobacterium angulatum in amelioration of hyperglycaemia and reduction of HbA1c levels. On the other hand, Levilactobacillus brevis has been previously reported to alleviate the progression of type 2 diabetes in animal models, via interplay of gut microflora, bile acid and NOTCH 1 signalling 72 . Also, Levilactobacillus brevis possess inhibitory effects on α-amylase and α-glucosidase activities, and has been reported to have anti-diabetic properties 73 .…”