Immunomodulation by probiotics and prebiotics in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy in patients suffering from chronic liver diseases and cirrhosis. Recent attention has been paid to the involvement of the gut-liver axis (GLA) in HCC pathogenesis. This axis results from a bidirectional, anatomical and functional relationship between the gastrointestinal system and the liver. Moreover, the complex network of interactions between the intestinal microbiome and the liver plays a crucial role in modulation of the HCC-tumor microenvironment, contributing to the pathogenesis of HCC by exposing the liver to pathogen-associated molecular patterns, such as bacterial lipopolysaccharides, DNA, peptidoglycans and flagellin. Indeed, the alteration of gut microflora may disturb the intestinal barrier, bringing several toll-like receptor ligands to the liver thus activating the inflammatory response. This review explores the new therapeutic opportunities that may arise from novel insights into the mechanisms by which microbiota immunomodulation, represented by probiotics, and prebiotics, affects HCC through the GLA.

The Gut–Organ Axis within the Human Body: Gut Dysbiosis and the Role of Prebiotics

“…Additionally, the beneficial effects of prebiotics on NAFLD can be attributed to decreased de novo lipogenesis, weight and fat loss, enhanced blood glucose control, restored GM, and decreased inflammation [127]. The function of prebiotics in hepatocellular carcinoma has also been investigated [128,129]. The primary mechanisms include the production of SCFAs, which positively affect the structure and function of the intestinal microbiota, primarily by controlling colonocyte function, promoting water and electrolyte absorption, decreasing intraluminal pH, inhibiting pathogen proliferation, modifying the immune homeostasis of the gut, and modulating the inflammatory response [129].…”

“…The function of prebiotics in hepatocellular carcinoma has also been investigated [128,129]. The primary mechanisms include the production of SCFAs, which positively affect the structure and function of the intestinal microbiota, primarily by controlling colonocyte function, promoting water and electrolyte absorption, decreasing intraluminal pH, inhibiting pathogen proliferation, modifying the immune homeostasis of the gut, and modulating the inflammatory response [129]. In addition, the enhancement of intestinal barrier function by modifying GM composition ameliorates conditions such as cirrhosis and may therefore prevent HCC [128].…”

Potential Effects of Regulating Intestinal Flora on Immunotherapy for Liver Cancer

“…Although the liver is not in direct contact with the microorganisms, it is closely connected to the intestine through the biliary tract, hepatic portal vein, and bile secretion. The intestine-liver axis plays an important role in the pathogenesis of HCC [21][22][23]. Ecological imbalance is the qualitative and quantitative changes in the intestinal microflora that may destroy the intestinal barrier and increase intestinal permeability.…”