Nature Communications

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

J John P. McElderry T Tongwu Zhang W Wei Zhao P Phuc H. Hoang S Samuel Anyaso-Samuel J Jian Sang A Azhar Khandekar C Caleb Hartman F Frank J. Colón-Matos M Mona Miraftab M Monjoy Saha O Olivia Lee S Sunandini Sharma K Kristine M. Jones B Bin Zhu M Marcos Díaz-Gay L Luis Mas O Oscar Arrieta E Eric S. Edell J Jacobo Martínez Santamaría M Matthew B. Schabath S Sai Yendamuri M Marta Manczuk J Jolanta Lissowska B Beata Świątkowska A Anush Mukeria O Oxana Shangina D David Zaridze I Ivana Holcatova V Vladimir Janout D Dana Mates S Simona Ognjanovic M Milan Savic M Milica Kontic Y Yohan Bossé B Bonnie E. Gould Rothberg D David C. Christiani V Valerie Gaborieau P Paul Brennan G Geoffrey Liu P Paul Hofman M Maria Pik Wong K Kin Chung Leung C Chih-Yi Chen C Chao Agnes Hsiung N Nathaniel Rothman C Charles Leduc M Marina K. Baine W William D. Travis L Lynette M. Sholl P Philippe Joubert R Robert Homer S Soo-Ryum Yang Q Qing Lan M Martin A. Nowak D David C. Wedge L Ludmil B. Alexandrov S Stephen J. Chanock E Emily Vogtmann C Christian C. Abnet (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD) J Jianxin Shi M Maria Teresa Landi

Abstract

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.

Download PDF View Original
APA MLA Chicago BibTeX RIS

Article Details

Volume / Issue Vol. 17, Issue 1
Published December 12, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (62)

J

John P. McElderry

T

Tongwu Zhang

W

Wei Zhao

P

Phuc H. Hoang

S

Samuel Anyaso-Samuel

J

Jian Sang

A

Azhar Khandekar

C

Caleb Hartman

F

Frank J. Colón-Matos

M

Mona Miraftab

M

Monjoy Saha

O

Olivia Lee

S

Sunandini Sharma

K

Kristine M. Jones

B

Bin Zhu

M

Marcos Díaz-Gay

L

Luis Mas

O

Oscar Arrieta

E

Eric S. Edell

J

Jacobo Martínez Santamaría

M

Matthew B. Schabath

S

Sai Yendamuri

M

Marta Manczuk

J

Jolanta Lissowska

B

Beata Świątkowska

A

Anush Mukeria

O

Oxana Shangina

D

David Zaridze

I

Ivana Holcatova

V

Vladimir Janout

D

Dana Mates

S

Simona Ognjanovic

M

Milan Savic

M

Milica Kontic

Y

Yohan Bossé

B

Bonnie E. Gould Rothberg

D

David C. Christiani

V

Valerie Gaborieau

P

Paul Brennan

G

Geoffrey Liu

P

Paul Hofman

M

Maria Pik Wong

K

Kin Chung Leung

C

Chih-Yi Chen

C

Chao Agnes Hsiung

N

Nathaniel Rothman

C

Charles Leduc

M

Marina K. Baine

W

William D. Travis

L

Lynette M. Sholl

P

Philippe Joubert

R

Robert Homer

S

Soo-Ryum Yang

Q

Qing Lan

M

Martin A. Nowak

D

David C. Wedge

L

Ludmil B. Alexandrov

S

Stephen J. Chanock

E

Emily Vogtmann

C

Christian C. Abnet

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD

J

Jianxin Shi

M

Maria Teresa Landi

Related Articles from this Journal

Synthesis of adaptive 15N-nitrosyl-Co7 nanocluster for electrocatalytic C–H functionalization

Chao Wu, Xu Zhang et al. Aug 2026 10.1038/s41467-026-76516-1

Pan-Ebolavirus nanoparticle vaccine provides protection in rodents from lethal infection by Zaire and Sudan viruses

Connor Weidle, Natalie Brunette et al. Aug 2026 10.1038/s41467-026-76114-1

Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk

Ludmila Prokunina-Olsson, Oscar Florez-Vargas et al. Aug 2026 10.1038/s41467-026-76157-4

Genome-wide annotation of human multi-nucleotide variants reveals widespread functional differences from single nucleotide variants

Weiwei Jin, Wen Cao et al. Aug 2026 10.1038/s41467-026-76470-y

Allele-specific chromatin architecture shapes imprinted domains and coordinates a distal enhancer and antisense transcription at the mouse Mest-Copg2 domain

Bongmin Bae, Katherine Gu et al. Aug 2026 10.1038/s41467-026-76506-3