Association of distinct microbial signatures with premalignant colorectal adenomas

Jonathan Wei Jie Lee; Damian R Plichta; Shreya Asher; Marisa Delsignore; Tiffany Jeong; Jessica McGoldrick; Kyle Staller; Hamed Khalili; Ramnik J Xavier; Daniel C Chung

doi:10.1016/j.chom.2023.04.007

Association of distinct microbial signatures with premalignant colorectal adenomas

Cell Host Microbe. 2023 May 10;31(5):827-838.e3. doi: 10.1016/j.chom.2023.04.007. Epub 2023 May 1.

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore 119228, Singapore; iHealthtech, National University of Singapore, Singapore 117599, Singapore; SynCTI, National University of Singapore, Singapore 117456, Singapore. Electronic address: jonathanlee@nus.edu.sg.
² Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
⁵ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Cancer Risk Assessment, Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: chung.daniel@mgh.harvard.edu.

PMID: 37130517
PMCID: PMC10477964 (available on 2024-05-10)
DOI: 10.1016/j.chom.2023.04.007

Abstract

Environmental exposures are a major risk factor for developing colorectal cancer, and the gut microbiome may serve as an integrator of such environmental risk. To study the microbiome associated with premalignant colon lesions, such as tubular adenomas (TAs) and sessile serrated adenomas (SSAs), we profiled stool samples from 971 participants undergoing colonoscopy and paired these data with dietary and medication history. The microbial signatures associated with either SSA or TA are distinct. SSA associates with multiple microbial antioxidant defense systems, whereas TA associates with a depletion of microbial methanogenesis and mevalonate metabolism. Environmental factors, such as diet and medications, link with the majority of identified microbial species. Mediation analyses found that Flavonifractor plautii and Bacteroides stercoris transmit the protective or carcinogenic effects of these factors to early carcinogenesis. Our findings suggest that the unique dependencies of each premalignant lesion may be exploited therapeutically or through dietary intervention.

Keywords: colonic adenoma; colorectal cancer; fecal microbiome; metagenomics; microbial communities.

MeSH terms

Adenoma*
Colonic Polyps* / pathology
Colonoscopy
Colorectal Neoplasms* / pathology
Humans

Association of distinct microbial signatures with premalignant colorectal adenomas

Authors

Affiliations

Abstract

MeSH terms

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