Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2021; 13(6): 495-508
Published online Jun 15, 2021. doi: 10.4251/wjgo.v13.i6.495
Familial adenomatous polyposis and changes in the gut microbiota: New insights into colorectal cancer carcinogenesis
Antonio Biondi, Francesco Basile, Marco Vacante
Antonio Biondi, Francesco Basile, Marco Vacante, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania 95123, Italy
Antonio Biondi, Francesco Basile, Marco Vacante, Multidisciplinary Research Center for Rare Diseases, University of Catania, Catania 95123, Italy
Author contributions: All authors contributed to the writing and reading of the manuscript and gave approval of the final version. All authors have read and agreed with publication of the manuscript.
Conflict-of-interest statement: The authors have no competing interests to declare.
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: Marco Vacante, MD, PhD, Academic Fellow, Doctor, Research Fellow, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, Catania 95123, Italy. marcovacante@yahoo.it
Received: February 20, 2021
Peer-review started: February 20, 2021
First decision: March 15, 2021
Revised: March 15, 2021
Accepted: May 8, 2021
Article in press: May 8, 2021
Published online: June 15, 2021
Processing time: 106 Days and 22.5 Hours
Abstract

Patients with familial adenomatous polyposis (FAP), an autosomal dominant hereditary colorectal cancer syndrome, have a lifetime risk of developing cancer of nearly 100%. Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer. Some gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, Clostridium difficile, Peptostreptococcus, and enterotoxigenic Bacteroides fragilis, could be implicated in colorectal carcinogenesis through different mechanisms, including the maintenance of a chronic inflammatory state, production of bioactive tumorigenic metabolites, and DNA damage. Studies using the adenomatous polyposis coliMin/+ mouse model, which resembles FAP in most respects, have shown that specific changes in the intestinal microbial community could influence a multistep progression, the intestinal “adenoma-carcinoma sequence”, which involves mucosal barrier injury, low-grade inflammation, activation of the Wnt pathway. Therefore, modulation of gut microbiota might represent a novel therapeutic target for patients with FAP. Administration of probiotics, prebiotics, antibiotics, and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP. The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.

Keywords: Familial adenomatous polyposis; Microbiota; Colorectal cancer; Polyps; Carcinogenesis; Bacteria

Core Tip: A number of studies have demonstrated that gut microbiota dysbiosis could be a key factor in colorectal carcinogenesis. The adenomatous polyposis coli (APC)Min/+ mouse model has been extensively used to study the underlying mechanisms of colorectal carcinogenesis in familial adenomatous polyposis. Interventions aimed at improving dysbiosis by administration of probiotics, prebiotics, or antibiotics could decrease colorectal cancer development in APC mutation carriers.