Tumor-resident bacteria in gastrointestinal cancers - from regulatory mechanisms to clinical implications

Sep 22, 2026

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The human microbiome is increasingly recognized as a key contributor to the tumor microenvironment (TME). Advances in sequencing technologies have identified intratumoral microbiota as central to gastrointestinal cancer development. This review consolidates evidence on tumor-resident bacteria in colorectal, gastric, and hepatocellular carcinoma, detailing how microbes influence carcinogenesis and progression through host gut barrier, tumor cell, anti-tumor immunity, and other TME components. It also evaluates translational value as diagnostic and prognostic biomarkers and impacts on therapeutic responses, supporting targeting the intratumoral microbiome for improved outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Introduction

Characteristics of intratumoral microbiota in gastrointestinal cancers

CRC

Gastric cancer

Hepatocellular carcinoma

Cancer Biol Med 2026. doi: 10.20892/j.issn.2095-3941.2025.0686 REVIEW Tumor-resident bacteria in gastrointestinal cancers: from regulatory mechanisms to clinical implications Ying Zhang 1*, Bingyu Tan2*, Qianying Zhou 1*, Lixia Xu 1, Lei Zhou2 1 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 2 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China | ABSTRACT | The human microbiome is increasingly recognized as a key contributor to the tumor microenvironment (TME) . Advances in sequencing technologies have revealed the pivotal role of intratumoral microbiota in the development of gastrointestinal cancers. This review summarizes current knowledge on the characteristics and functional mechanisms of tumor-resident bacteria in colorectal, gastric, and hepatocellular carcinoma. We describe how these microbes affect carcinogenesis and disease progression through multiple pathways, including interactions between the microbiota and the host gut barrier, tumor cells, anti-tumor immunity, and other non-cellular components of the TME. In addition, the translational potential of intratumoral microbiota as diagnostic and prognostic biomarkers, as well as the influence on therapeutic responses, is discussed. A growing understanding of tumor-microbe interactions not only deepens insight into cancer biology but also opens new directions for innovative diagnostic and therapeutic strategies, highlighting the potential of targeting the intratumoral microbiome to improve patient outcomes in gastrointestinal oncology. | | --- | --- | | KEYWORDS | Intratumoral microbiota; gastrointestinal cancers; tumor microenvironment; microbiome-host interactions | Introduction The human gut microbiome is comprised of communities of bacteria, fungi, viruses, archaea, and protozoa, together with their metabolites. These microorganisms inhabit different anatomic regions of the gastrointestinal tract and have co-evolved with the host for tens of millions of years, playing an essential role in maintaining human health. Dysbiosis of the gut microbiome contributes to the complex mechanisms underlying tumorigenesis in gastrointestinal cancers. Although bacteria were observed in tumor tissues >100 years ago, tumors were long considered sterile. Owing to the extremely low microbial burden in tumors and the lack of sensitive detection methods to exclude contamination, the presence of intratumoral bacteria was not widely acknowledged or studied. Over the past decade, progress in next-generation sequencing (NGS) technologies, including 16SrRNA amplicon *These authors contributed equally to this work. Correspondence to: Lixia Xu and Lei Zhou E-mail: [xulixia@mail.sysu.edu.cn](xulixia@mail.sysu.edu.cn) and [zhoulei39@mail.sysu.edu.cn](zhoulei39@mail.sysu.edu.cn) ORCID ID: [https://orcid.org/0000-0002-1818-6267](https://orcid.org/0000-0002-1818-6267) and [https://orcid.org/0000-0003-4709-3198](https://orcid.org/0000-0003-4709-3198) Received November 15, 2025; accepted February 27, 2026; published online April 20, 2026. Available [at www.cancerbiomed.org](at www.cancerbiomed.org) ©2026 The Authors. Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4 .0) and metagenomic shotgun sequencing, has provided new insights into intratumoral microbial communities. Using 16SrDNA PCR analysis of tissues from seven human cancer types (bone, brain, breast, lung, melanoma, ovary, and pancreas), Nejman et al.1 reported in 2020 that most tumors and adjacent normal tissues harbor diverse bacteria that are primarily localized within cancer and immune cells. Since then, intratumoral bacteria have become a major focus of research with the potential to reshape current concepts of tumor biology. This article reviews the characteristics of intratumoral microorganisms in major gastrointestinal cancers, particularly colorectal can

FAQs

What is the role of tumor-resident bacteria in the tumor microenvironment (TME)?

Tumor-resident bacteria are described as contributors to the TME and key drivers of gastrointestinal cancer development by shaping interactions with the host gut barrier, tumor cells, and anti-tumor immunity.

Which gastrointestinal cancers does the review focus on?

The review focuses mainly on colorectal cancer (CRC), gastric cancer (GC), and hepatocellular carcinoma (HCC).

How might intratumoral microbiota be used clinically?

The review discusses translational potential of intratumoral microbiota as diagnostic and prognostic biomarkers and its influence on therapeutic responses.

Sep 22, 2026

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