Exploring the causal role of the human gut microbiome in colorectal cancer: Application of Mendelian randomization
Year: 2022
Type: preprint
Study design: Observational Study
Abstract: Aim The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. Materials and methods We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n=3,890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Results Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Conclusions Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
Source: medRxiv
Authors: Charlie Hatcher, George Richenberg, Samuel Waterson, Long H. Nguyen, Amit D. Joshi, Robert Carreras-Torres, Victor Moreno, Andrew T. Chan, Marc Gunter, Yi Lin, Conghui Qu, Mingyang Song, Graham Casey, Jane C Figueiredo, Stephen B Gruber, Jochen Hampe, Heather Hampel, Mark A Jenkins, Temitope O Keku, Ulrike Peters, Catherine M Tangen, Anna H Wu, David A Hughes, Malte C Rühlemann, Jeroen Raes, Nicholas J. Timpson, Kaitlin H. Wade
Institutions: University of Bristol, MRC Integrative Epidemiology Unit, North Bristol NHS Trust, Massachusetts General Hospital, Institut d'Investigació Biomédica de Bellvitge, Institut d'Investigació Biomèdica de Girona, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universitat de Barcelona, Centre international de recherche sur le cancer, Fred Hutch Cancer Center, Harvard University, University of Virginia, Cedars-Sinai Medical Center, University of Southern California, USC Norris Comprehensive Cancer Center, Technische Universität Dresden, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, The University of Melbourne, University of North Carolina at Chapel Hill, Christian-Albrechts-Universität zu Kiel, VIB-KU Leuven Center for Microbiology, KU Leuven
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1131969086, G1318839879, Human gut Microbiome, gene Expression and Colorectal Cancer: Assigning causal roles from a novel Mendelian randomization perspective., G323433674, G324601231, G434337789, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G5413097837
OpenAlex ID: W4306646679