Variation in oral microbiome is associated with future risk of lung cancer among never-smokers

Abstract

ObjectiveTo prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.Design and settingA nested case–control study within two prospective cohort studies, the Shanghai Women’s Health Study (n=74 941) and the Shanghai Men’s Health Study (n=61 480).ParticipantsLifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).Main outcomes and measuresMetagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.ResultsSubjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: ptrend=0.05; Simpson: ptrend=0.04; Observed Species: ptrend=0.64). No case–control differences were apparent for beta diversity (pMiRKAT=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (ORlow 1.00 (reference), ORmedium 0.61 (95% CI 0.32 to 1.18), ORhigh 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (ORlow 1.00 (reference), ORmedium 0.66 (95% CI 0.35 to 1.25), ORhigh 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (ORlow 1.00 (reference), ORmedium 1.49 (95% CI 0.73 to 3.08), ORhigh 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (ORlow 1.00 (reference), ORmedium 2.15 (95% CI 1.03 to 4.47), ORhigh 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.ConclusionsOur prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.

Relationships Between Oral Microecosystem and Respiratory Diseases

“…Variations in oral microbiome have been associated with future risk of lung cancer among never-smokers. Lower microbial diversity and richness of salivary microbiota are found in non-smoking lung cancer patients and the abundance of certain specific taxa is associated with altered risk ( Yang et al, 2018 ; Hosgood et al, 2021 ). More specifically, a greater abundance of the Bacilli class and Lactobacillales order in saliva was associated with an increased risk of lung cancer, while a greater abundance of Spirochaetia and Bacteroidetes in saliva was associated with a decreased risk of lung cancer ( Hosgood et al, 2021 ).…”

“…Lower microbial diversity and richness of salivary microbiota are found in non-smoking lung cancer patients and the abundance of certain specific taxa is associated with altered risk ( Yang et al, 2018 ; Hosgood et al, 2021 ). More specifically, a greater abundance of the Bacilli class and Lactobacillales order in saliva was associated with an increased risk of lung cancer, while a greater abundance of Spirochaetia and Bacteroidetes in saliva was associated with a decreased risk of lung cancer ( Hosgood et al, 2021 ). Furthermore, functional analysis indicates that salivary microbiome in non-smoking female lung cancer patients is related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis ( Yang et al, 2018 ).…”

Alterations in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis

“…The abundance of Veillonella , which is another dominant genus of the oral microbiota ( 56 ), was higher in the cancer group, although it did not achieve statistical significance. Overabundance of oral bacteria was found to be correlated with a spectrum of malignancies including but not limited to colorectal cancer ( 57 ), pancreatic cancer ( 58 , 59 ) and lung cancer ( 60 ). Though the relationship between oral microbiome and GC has not yet been clarified, oral microbiome has been considered as a potential biomarker for non-invasive diagnosis of GC ( 44 ).…”

Prospective study of oral microbiome and gastric cancer risk among Asian, African American and European American populations

“…6 Multiple oral microbial taxa have been reported to be associated with increased risks of cancers. [7][8][9][10][11] In addition, a recent prospective cohort study showed that poor oral health was associated with increased gastric cancer risk. 12 To date, only four case-control studies have explored the relationship between oral microbiome and gastric cancer.…”