Gut microbiota-considered pharmacotherapeutic management of hepatocellular carcinoma

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

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

Despite the encouraging results about the modulation of ICIs response by FMT in other solid tumors (melanoma, colorectal cancer, renal cell carcinoma and mixed solid-tumor), whether this strategy is effective and safe in HCC remains to be established in prospective HCC-specific trials. The availability of a preliminary detailed 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. Moreover, the eventual discovery of specific bacterial patterns in responders and non-responders to ICIs could open the possibility to administer FMT as a standard of care at least in selected patients with the target of re-stablishing HCC response to ICIs.