Microbiome analysis of 940 lung cancers in never-smokers reveals lack of clinically relevant associations

In spite of the growing interest in the microbiome in human cancer, there are currently only small-scale lung cancer microbiome studies conducted directly on tissue. As part of the Sherlock-Lung study, we studied the microbiomes of 940 lung cancers (4090 samples) in never smokers (LCINS) directly from lung tissue using three data types: 16S rRNA gene sequencing (16S), whole-genome sequencing (WGS) with paired blood, and RNA-seq. We observe very low biomass and few microbiome associations in LCINS using 16S and WGS tissue. Using RNA-seq, we observe more total microbial reads, and decreased relative abundance of several commensal bacteria at the genus and species levels in tumors relative to paired normal lung tissue. Among all datasets, we see no consistent associations between the lung tissue microbiome, or circulating bacterial DNA, and any available demographic and clinical features, including age, sex, genetic ancestry, second-hand tobacco smoking exposure, LCINS histology, stage, and overall survival. We also observe no microbiome associations with any human genomic alterations within the same samples. Every null result should be interpreted with caution given the possibility of future methodological breakthroughs. However, all together, using multiple data types in nearly 1000 patients, we find no substantive role for the lung cancer microbiome in treatment-naïve LCINS.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-12-12
DOI
https://doi.org/10.1038/s41467-025-66780-y
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Microbiome analysis of 940 lung cancers in never-smokers reveals lack of clinically relevant associations

Beata Świątkowska, Jolanta Lissowska, Paul Brennan, David C. Wedge et al.
Nature Communications
Gut microbiota and health
article

Microbiome analysis of 940 lung cancers in never-smokers reveals lack of clinically relevant associations

Beata Świątkowska, Jolanta Lissowska, Paul Brennan, David C. Wedge, Monjoy Saha, Christian C. Abnet, Chao A. Hsiung, Dana Mateș, Luis A. Mas, Samuel Anyaso‐Samuel, Oxana Shangina, Ivana Holcátová, Kristine M. Jones, John McElderry, William D. Travis, Zhao Wei, Milan Savić, Milica Kontić, Kin Chung Leung, Jian Sang, Olivia W. Lee, Valérie Gaborieau, Marina K. Baine, Vladimí­r Janout, Bonnie E. Gould Rothberg, Tongwu Zhang, Azhar Khandekar, Robert Homer, Sai Yendamuri, Matthew B. Schabath, Soo‐Ryum Yang, Simona Ognjanovic, Chih-Yi Chen, Bin Zhu, Yohan Bossé, Emily Vogtmann, Phuc H. Hoang, Ludmil B. Alexandrov, Martin A. Nowak, Maria Teresa Landi, Marta Mańczuk, Marcos Díaz‐Gay, Paul M Hofman, Lynette M. Sholl, David C. Christiani, Philippe Joubert, Stephen J. Chanock, Frank J. Colón-Matos, Geoffrey Liu, Jianxin Shi, Qing Lan, Charles Leduc, Maria Pik Wong, Sunandini Sharma, Nathaniel Rothman, Juan Miguel Santamaría, Eric S. Edell, Caleb Hartman, David Zaridze, Anush Mukeria, Óscar Gerardo Arrieta Rodríguez, Mona Miraftab
article en

Abstract

In spite of the growing interest in the microbiome in human cancer, there are currently only small-scale lung cancer microbiome studies conducted directly on tissue. As part of the Sherlock-Lung study, we studied the microbiomes of 940 lung cancers (4090 samples) in never smokers (LCINS) directly from lung tissue using three data types: 16S rRNA gene sequencing (16S), whole-genome sequencing (WGS) with paired blood, and RNA-seq. We observe very low biomass and few microbiome associations in LCINS using 16S and WGS tissue. Using RNA-seq, we observe more total microbial reads, and decreased relative abundance of several commensal bacteria at the genus and species levels in tumors relative to paired normal lung tissue. Among all datasets, we see no consistent associations between the lung tissue microbiome, or circulating bacterial DNA, and any available demographic and clinical features, including age, sex, genetic ancestry, second-hand tobacco smoking exposure, LCINS histology, stage, and overall survival. We also observe no microbiome associations with any human genomic alterations within the same samples. Every null result should be interpreted with caution given the possibility of future methodological breakthroughs. However, all together, using multiple data types in nearly 1000 patients, we find no substantive role for the lung cancer microbiome in treatment-naïve LCINS.

Nature CommunicationsVol. 17(1)
Leidos (United States) (US), Brigham and Women's Hospital (US), Roswell Park Comprehensive Cancer Center (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Harvard University (US), University of Miami (US), National Health Research Institutes (TW), Nofer Institute of Occupational Medicine (PL), Charles University (CZ), Queen Mary Hospital (CN), Princess Margaret Cancer Centre (CA), University of Manchester (GB), Centre Hospitalier Universitaire de Nice (FR), Moffitt Cancer Center (US), Yale University (US), Massachusetts General Hospital (US), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES), University Hospital in Motol (CZ), Chung Shan Medical University Hospital (TW), Instituto Nacional de Cardiologia (BR), Centar za Promociju Nauke (RS), University of Miami Hospital (US), National Institute of Oncology (HU), National Institute of Public Health (LA), Instituto Nacional de Enfermedades Neoplásicas (PE), Cancer Research UK Manchester Institute (GB), Frederick National Laboratory for Cancer Research (US), La Jolla Bioengineering Institute (US), Institut universitaire de cardiologie et de pneumologie de Québec (CA), National Cancer Institute (US), Centre Hospitalier de l’Université de Montréal (CA), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Instituto Nacional de Cancerología (MX), Centre international de recherche sur le cancer (FR), Université Laval (CA), Division of Cancer Epidemiology and Genetics, Palacký University Olomouc (CZ), University of Hong Kong (HK), Chung Shan Medical University (TW)
U.S. Department of Health and Human Services, World Health Organization, Yale University, Harvard University, Ministry of Health and Welfare, Moffitt Cancer Center, Ministry of Science and Technology, Taiwan, Centre Hospitalier Universitaire de Nice, Connaught Fund, INCLIVA Instituto de Investigación Sanitaria, National Institutes of Health, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Fonds de Recherche du Québec - Santé, Health and Medical Research Fund, National Cancer Institute
Openalex Percentile: Top 64%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.