Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study

Sep 24, 2026

Evidence from observational studies and clinical trials links gut microbiota with cancer, yet causality remains unclear. Using two-sample Mendelian randomisation, the study leverages gut microbiota genetic liability instruments across phylum to genus levels and cancer data from the IEU Open GWAS project. A bi-directional MR framework evaluates causal direction across eight cancer types. Findings identify multiple causal relationships and strong associations, supporting gut microbiota as causally involved in cancers and suggesting new mechanistic research opportunities.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Gut microbiota and disease risk

Limitations of observational and trial evidence

Role of GWAS and Mendelian randomisation

Long etal. BMC Medicine (2023) 21:66 [https://doi.org/10.1186/s12916-023-02761-6](https://doi.org/10.1186/s12916-023-02761-6) BMC Medicine RESEARCH ARTICLE Open Access Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study Yiwen Long1,2†, Lanhua Tang1,2†, Yangying Zhou1,2, Shushan Zhao2,3* and Hong Zhu1,2* Abstract Background Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined. Methods We first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations. Results We identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets. Conclusions Our MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer. Keywords Gut microbiota, Cancer, Mendelian randomisation, Genetics, SNPs Background Gut microbiota residing in the gastrointestinal tract can be considered a potential environmental factor influencing human life. Currently, the gut microbiota has been †Yiwen Long and Lanhua Tang contributed equally to this work. *Correspondence: Shushan Zhao [zhaoshuiquan@126.com](zhaoshuiquan@126.com)[ ](zhaoshuiquan@126.com)Hong Zhu [zhuhong0719@126.com](zhuhong0719@126.com) 1 Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China 3 Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China implicated as a risk or preventive factor for a variety of diseases, including cancers, and is closely associated with the onset of colorectal cancer (CRC) [1]. Conversely, it has been pointed out that cancer also affects the gut microbiota in mice, which could induce gut microbiota disorders and cancer growth [2]. In contrast to observational studies, randomised controlled trials of gut microbiota could potentially help establish a causal relationship. Unfortunately, owing to the influence of objective factors, such as technology and research methods, the screening of strains involved in early diagnosis and prognosis still has great limitations. Consequently, most of the current research conclusions are based on observation of the composition and changes in the gut microbiota inpatients’ faeces and on the results of trials in which gut © The Author(s) 2023. 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 inten

FAQs

What method was used to test causality between gut microbiota and cancer?

The study used two-sample Mendelian randomisation (MR) to evaluate whether genetic liability in the gut microbiome is causally associated with cancer.

Where did the cancer and genetic data come from?

Cancer data were obtained from the IEU Open GWAS project, while gut microbiota instruments were identified using information from phylum through genus levels.

Did the study assess the direction of causal relationships?

Yes. It performed a bi-directional MR analysis to examine the direction of the causal relations between gut microbiota and cancer.

Sep 24, 2026

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