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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1616-1631
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1616
Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment
Ilenia Bartolini, Matteo Risaliti, Rosaria Tucci, Paolo Muiesan, Maria Novella Ringressi, Antonio Taddei, Amedeo Amedei
Ilenia Bartolini, Matteo Risaliti, Rosaria Tucci, Paolo Muiesan, Maria Novella Ringressi, Antonio Taddei, Department of Experimental and Clinical Medicine, University of Florence, Azienda Ospedaliero Universitaria Careggi (AOUC), Florence 50134, Italy
Amedeo Amedei, Department of Experimental and Clinical Medicine, SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliero Universitaria Careggi (AOUC), Florence 50134, Italy
Author contributions: All authors contributed to conceptualization and design of the study; Bartolini I, Risaliti M and Tucci R wrote the original draft; all the authors contributed to critical revision of the article and approved the final version of the paper; Muiesan P, Taddei A and Amedei A supervised preparation of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Amedeo Amedei, PhD, Professor, Department of Experimental and Clinical Medicine, SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliero Universitaria Careggi (AOUC), Largo Brambilla 3, Florence 50134, Italy.amedeo.amedei@unifi.it
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: April 19, 2021
Revised: April 25, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: November 15, 2021
Abstract

Liver cancer is a leading cause of death worldwide, and hepatocellular carcinoma (HCC) is the most frequent primary liver tumour, followed by cholangiocarcinoma. Notably, secondary tumours represent up to 90% of liver tumours. Chronic liver disease is a recognised risk factor for liver cancer development. Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration. The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota, its metabolites and the liver through the portal flow. The interplay between the immune system and gut microbiota is also well-known. Although primarily resulting from experiments in animal models and on HCC, growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours. Despite the curative intent of “traditional” treatments, tumour recurrence remains high. Therefore, microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment. Furthermore, microbiota could represent a non-invasive biomarker for early liver cancer diagnosis. This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development, focusing on the potential therapeutic implications.

Keywords: Gut microbiota, Immune system, Liver cancer, Primary liver cancer, Colorectal liver metastasis, Liver cancer treatment

Core Tip: Liver cancer is a worldwide leading cause of death. Growing evidence suggested a pathogenetic role of the gut microbiota and immune system in liver cancer development. Although there have been rapid developments in metagenomic science, definitive and complete knowledge of these processes is still far from being acquired. However, targeting both microbiota and the immune system could represent an appealing therapeutic option alone or as a boost of conventional treatments. Finally, the microbiota signature evaluation could represent a potential novel, non-invasive biomarker for early diagnosis.