Cholecystectomy-associated gut microbiota dysbiosis promotes colorectal carcinogenesis - from epidemiological controversy to FXR-centered mechanistic insights

Sep 22, 2026

Cholecystectomy is a common surgery worldwide, yet its relationship with colorectal cancer (CRC) risk remains disputed. Recent research links gut microbiota disruption and bile acid remodeling to CRC development. This review integrates epidemiological findings with molecular mechanisms, centering on the microbiota–bile acid–FXR signaling axis, and outlines a personalized prevention strategy combining demographic risk signals, microbial signatures, and metabolic biomarkers.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Current status of cholecystectomy

Summary of contents

Core findings

Conclusion and significance

Highlights

Keywords

Huang Journal of the Egyptian National Cancer Institute (2026) 38:20 [https://doi.org/10.1186/s43046-026-00360-z](https://doi.org/10.1186/s43046-026-00360-z) Journal of the Egyptian National Cancer Institute REVIEW Open Access Cholecystectomy-associated gut microbiota dysbiosis promotes colorectal carcinogenesis: from epidemiological controversy to FXRcentered mechanistic insights Zhongqin Huang1* Abstract Background and objective Cholecystectomy is one of the most common surgeries worldwide, yet its association with colorectal cancer (CRC) risk remains controversial. Recent advances have linked gut microbiota and bile acid alterations to this risk. This review synthesizes epidemiological evidence and molecular mechanisms, focusing on the microbiota-bile acid-FXR signaling axis, and proposes a personalized prevention framework. Summary of contents Epidemiological data reveal consistent patterns: proximal colon cancer predominance, higher risk in women, and peak incidence 5–15 years post-surgery. Cholecystectomy induces gut microbiota dysbiosis (decreased Bifidobacterium breve, increased Ruminococcus gnavus) and bile acid disturbances (elevated TUDCA/ GUDCA, altered protective bile acids), which converge on FXR signaling. Core findings The FXR signaling axis is a central hub. Yang et al. (Nat Commun 2025) showed that cholecystectomyinduced microbiota shifts alter bile acids, suppress FXR, disrupt FXR/β-catenin interaction, and promote tumorigenesis. The FXR agonist obeticholic acid prevents these effects preclinically, but systemic toxicity limits clinical use. Conclusion and significance We propose personalized risk stratification integrating demographics, microbial signatures, and metabolic biomarkers. Interventions include gut-restricted FXR agonists, probiotics, and Mediterranean diet. Future directions include prospective validation and dynamic network modeling. Highlights • Cholecystectomy increases proximal colon cancer risk, especially in women, with a 5–15 year latency. • The gut microbiota-bile acid-FXR axis is the central mechanistic pathway. • TUDCA/GUDCA are context-dependent: protective pharmacologically but FXR-suppressive after cholecystectomy. • Systemic FXR agonists (OCA) have safety limitations; gut-restricted agonists are more viable. • A multi-hit model explains the latency gap: cumulative DNA damage and clonal expansion over years. *Correspondence: Zhongqin Huang [171076060@qq.com](171076060@qq.com) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Huang Journal of the Egyptian National Cancer Institute (2026) 38:20 Page 2 of 18 Keywords Cholecystectomy, Colorectal cancer, Gut microbiota, Bile acids, FXR, Personalized prevention Introduction Current status ofcholecystectomy: the most common biliary surgery worldwide Since the first cholecystectomy was performed by Langenbuch in 1882, this procedure has evolved dramatically, particularly with the advent of laparoscopic techniques. In th

FAQs

Why is the link between cholecystectomy and colorectal cancer risk still controversial?

The association with CRC risk is debated despite widespread use of the surgery. This review explains how microbiota and bile acid changes provide a mechanistic basis that can reconcile epidemiological observations.

What is the central mechanistic pathway emphasized in the review?

The microbiota–bile acid–FXR signaling axis. Evidence described in the review shows cholecystectomy-induced microbiota shifts alter bile acids and suppress FXR-related signaling.

How do interventions such as FXR agonists, probiotics, and diet fit into prevention?

The review proposes a personalized framework including gut-restricted FXR agonists, probiotics, and a Mediterranean diet. It also notes that systemic FXR agonists may face safety limitations.

Sep 22, 2026

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