MicrobiotaMi Comment 23_21  by Marco Tonelli

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

This article was published in the: Thorax. 2021 Mar;76(3):256-263. doi: 10.1136/thoraxjnl-2020-215542. Epub 2020 Dec 14. PMID: 33318237

Lung cancer and oral microbiota: possible connections in never-smokers

Lung cancer is the first cause of death among cancer-related deaths. The majority of cases is related to tobacco smoking, nevertheless, 25% of lung cancer cases occur in non-smokers. As we already know, there are lots of other risk factors, such as household and outdoor air pollution, secondhand tobacco smoke, radon exposure and so on. The study by Hosgood et al., published on Thorax, aims at finding an association between oral microbiome and lung cancer in people who have never smoked in their lives.

The study involves patients from two large cohorts of people: the Shanghai Women’s Health Study (SWHS) and the Shanghai Men’s Health Study (SMHS), consisting of more than 60000 subjects. It is based upon oral rinse samples collected at baseline and then the patients were followed prospectively. In seven years of follow-up, among the SWHS cohort there were 90 cases of lung cancer in never-smoker women, while in the SMHS 24 cases occurred. Controls were identified matching them to the cases by sex, age, timing of sample collection, antibiotic use before collection and menopausal status for women. So, overall, the study consisted of 114 case-control pairs of patients.

A metagenomic shotgun sequencing of the baseline oral rinse samples was conducted to evaluate any possible differences in oral microbiota composition of the two group of patients. The first thing that was noticed by the study group was that patients with an increased alpha diversity, have a decreased risk of lung cancer, in comparison with subjects who have a lower microbial diversity.

As for the actual composition of the oral microbiota, different associations resulted from this study: among the Spirochaetes phylum, Spirochaetia class was more abundant in people who didn’t develop lung cancer. On the other hand, among the Firmicutes phylum, the Bacilli class, and more specifically the Lactobacillales order, was more abundant in people who developed lung cancer. Bacteroidetes, instead, was associated with a lower risk of lung cancer both at the class and family levels. The associations mentioned above were observed both for young (<61 years) and for old subjects (>61) and were similar both for men and women.

This is the first prospective study which examines the possible association between oral microbiota and lung cancer in a cohort of never-smokers. It is not yet clear whether oral microbiota could play an etiological role in this kind of cancer or if it just represents a disease or immunological marker. It is also crucial to understand how much air pollution and other environmental factors can influence the composition of oral microbiota. Besides, if oral microbiota composition actually acts as a risk factor for lung cancer, we should try to understand how it can lead to such a disease: in previous studies a relative abundance of Bacteroidetes and Firmicutes was proved to be associated with clinically stable COPD, while an abundance of Lactobacillales in sputum was associated with lung cancer in another study by Hosgood et al. (Environ Mol Mutagen 2014;55:643–51). One of the hypotheses about the possible pathogenesis is that some microbial changes in oral microbiota may lead to the production of DNA-damaging metabolites and, thus, to the carcinogenesis process.

Of course, these represent preliminary results and much more data worldwide need to be analyzed in order to assess whether there is a clear link between lung cancer pathogenesis and oral microbiota. Anyway, these results evidence how further research should focus on the role of oral microbiota in respiratory diseases.

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