Lactobacillus bulgaricus ATCC 11842 Exopolysaccharides Suppress Hepatic Inflammatory Signaling and Tumorigenesis in a DEN-Induced Rat Model via TLR2/STAT3/P38-MAPK Inhibition

Abstract

Growing evidence supports probiotics as a beneficial, economical, and non-toxic strategy for the control and prevention of hepatocellular carcinoma (HCC). Exopolysaccharides synthesized by specific lactic acid bacteria demonstrate significant health-promoting effects, such as anticancer and immune-regulating properties.

This research focused on assessing the immune-regulating capabilities of exopolysaccharides (EPSs) obtained from Lactobacillus bulgaricus ATCC 11842 in male rats with hepatocellular carcinoma (HCC), experimentally induced by diethylnitrosamine (DEN) and gamma irradiation (IR), aiming to determine their preventive or therapeutic value. Elevations in hepatic markers including MDA, IL-17, TGF-β1, STAT3, and p38MAPK were observed in biochemical assessments, along with raised serum levels of ALT and γ-GT.

Moreover, a notable increase in the hepatic expression of the TLR2 gene was detected. EPS administration, either as a preventive or therapeutic approach, led to significant improvements in the majority of the assessed biochemical and molecular markers. The liver tissues' histological findings matched the biochemical results that had been recovered. In conclusion, exopolysaccharides derived from Lactobacillus bulgaricus ATCC 11842 effectively suppress hepatocellular carcinoma by modulating the pro-inflammatory TLR2/STAT3/P38-MAPK signaling pathway. Therefore, in individuals at risk, our novel EPSs from Lactobacillus bulgaricus ATCC 4356 may serve as a safe, effective, and promising probiotic candidate for the prevention of hepatocarcinogenesis.