Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment

Abstract

Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.

Keywords: Carcinogenesis; Fecal microbiota transplantation; Gut microbiota; Gut–liver axis; Hepatocellular carcinoma; Immune checkpoint inhibitors.

Figure 1

Interaction between Bacterial Lipopolysaccharides and Toll-like receptor 4 signaling pathway in hepatocellular carcinoma development. LPS: Lipopolysaccharides; MyD88: Myeloid differentiation primary response protein 88; IRAK1/4: IL-1 receptor associated kinase 1/4; TRAF6: TNF receptor associated factor 6; TAK1: TGF-activated kinase 1; TAB2/3: TAK1-binding protein 2/3; NEMO: NF-kappa-B essential modulator; IKB: Inhibitor of nuclear factor kappa-B; NF-κB: Nuclear factor kappa B.