The multifaceted role of microbiota in liver cancer: pathogenesis, therapy, prognosis, and immunotherapy

Abstract

Accumulating evidence suggests that the progression of hepatocellular carcinoma (HCC) is intricately associated with dynamic alterations in microbiota composition. Disruption of gut microbial homeostasis enables pathogenic gut bacteria to translocate to the liver via the gut-liver axis, where they modulate the tumor microenvironment to promote HCC development. Also, they are associated with anti-tumor immune responses. Studies have confirmed that the microbiota exhibits potential as a biomarker for predicting immunotherapy responses, and its can improve clinical efficacy in the treatment of HCC.This review systematically evaluates current evidence elucidating the regulatory mechanisms by which the microbiota governs the progression of HCC, and explores its synergistic interactions with therapeutic strategies for HCC.

Keywords: carcinogenesis; hepatocellular carcinoma; immunotherapy; microbiota; prognosis; therapy.

Figure 1

The gut-liver axis is a crucial body function. Commensal gut bacteria and microbial metabolites travel to the liver via the portal vein, while bile acids and other bioactive substances are delivered through the biliary tract. The figure was created using BioRender.com.

Figure 2

Changes in the intestinal and intratumoral microbiota during hepatocarcinogenesis. Intestinal barrier and liver damage can be caused by some external factors, including a high-fat diet, alcohol, diseases, and viruses. Furthermore, the intestinal and intratumoral microbiotas are disrupted, causing dysbiosis. Moreover, intratumoral tissues and intestinal sites comprise specific pathogenic bacteria, which exert their cancer-promoting effects through specific mechanisms. HBV, hepatitis B virus; HCV, hepatitis C virus; HSCs, hepatic stellate cells; SASP, senescence-associated secretory phenotype; LTA, lipoteichoic acid; DCA, deoxycholic acid. The figure was created using BioRender.com.

Figure 3

Potential strategies based on gut microbiota modulation for preventing HCC and chronic liver disease. Different strategies have different prevention and treatment mechanisms. LBGG, Lactobacillus rhamnosus GG; LC-705, Lactobacillus rhamnosus LC-705; NKT, natural killer T; LSEC, liver sinusoidal endothelial cells; FMT, fecal microbiota transplantation; NAFLD, nonalcoholic fatty liver disease; NASH, Non-alcoholic steatohepatitis; AIH, Autoimmune hepatitis. Figure created with BioRender.com.

Figure 4

Potential mechanisms underlying the inhibitory effects of gut microbiota modulators against hepatocellular carcinoma. HCC, hepatocellular carcinoma; GPR43, G coupled-protein receptor 43; NKT, natural killer T; IFN-γ, interferon-γ; MDSC, myeloid-derived suppressor cell; LPS, lipopolysaccharide. Figure created with BioRender.com.