Gut microbiota-considered pharmacotherapeutic management of hepatocellular carcinoma.

Abstract

Introduction: Treatment efficacy for hepatocellular carcinoma (HCC) remains limited. Increasing evidence indicates that gut microbiota may influence clinical outcomes and toxicity.

Areas covered: Our review synthesizes recent literature from PubMed and Wiley Online Library regarding gut microbiota, microbial metabolites, HCC and immune checkpoint inhibitors (ICIs) by analyzing the main research frameworks and identifying research gaps. Clinical studies suggest that microbial diversity and specific taxa (Akkermansia, Bifidobacterium, Faecalibacterium, Ruminococcus), may be associated with improved responses to ICIs. Microbiota-targeted approaches (fecal microbiota transplantation FMT, probiotics, engineered bacteria, diet, and postbiotics, are biologically promising but remain experimental in HCC.

Expert opinion: Despite the encouraging results about modulation of ICIs response by FMT in other solid tumors, whether this strategy is effective in HCC remains to be established in prospective HCC-specific trials. A preliminary characterization of gut microbial before undertaking HCC treatment would be tempting, especially if it could lead to a more precision-tailored approach with the possibility to foresee, within certain limits, the therapeutic outcome. The eventual discovery of specific bacterial patterns in responders and non-responders to ICIs could open the possibility to administer FMT as standard of care at least in selected patients with the target of re‑establishing HCC response to ICIs.