Mouth Bacteria Linked to Lung Cancer Risk in Never Smokers

By Megan Brooks

January 04, 2021

NEW YORK (Reuters Health) - The type and abundance of bacteria found in the mouth may be associated with lung-cancer risk in people who have never smoked, according a new study.

"When taken together, the limited but growing body of literature suggests that decreased microbial diversity and increased abundance of taxa within the Firmicutes phylum, and more specifically Lactobacillales, in the respiratory tract, may be associated with an increased risk of lung cancer," Dr. Dean Hosgood, Einstein College of Medicine, in New York City, told Reuters Health by email.

In a paper in Thorax, Dr. Hosgood and colleagues note that about a quarter of cases of lung cancer occur in non-smokers and known risk factors, such as exposure to second hand smoke, radon and air pollution, and family history of lung cancer don't fully explain this.

Past research has found ties between gastrointestinal cancers and the gut microbiome. The type and volume of bacteria found in the mouth have been tied to various cancers, including pancreatic cancer.

In one recent prospective study, an increased abundance of oral commensal bacteria was associated with a lower risk for head and neck squamous-cell cancer, "providing evidence that microbiota outside the gut may also be associated with cancer risk," the researchers note in their paper.

To investigate further, they evaluated bacterial diversity and abundance using metagenomic shotgun sequencing on oral rinse samples collected at baseline from participants in the Shanghai Women's Health Study and the Shanghai Men's Health Study, whose health was monitored every two to three years after enrollment between 1996 and 2006. All participants were lifelong nonsmokers.

Using a nested case-control design, they matched 90 women and 24 men who developed lung cancer with 114 age- and sex-matched individuals who did not develop lung cancer.

They found lower oral microbiota alpha diversity, but not beta diversity, was associated with an increased risk of lung cancer.

Additionally, increased relative abundance within the Bacteroidetes and Spirochaetes phyla was associated with a reduced risk of lung cancer, whereas increased abundance within the Firmicutes phylum was associated with an increased risk of lung cancer.

The associations remained when the analysis was restricted to people who had not taken antibiotics in the week before sample collection and after excluding those diagnosed with lung cancer within two years after the oral rinse sample was collected.

"To the best of our knowledge, this is the first prospective study to evaluate the oral microbiome and risk of lung cancer in never-smokers. Given the novelty of our findings and the limited sample size, replication studies are essential," the researchers write.

"Since our analysis was observational and etiological by design, we can't draw clinical implications," Dr. Hosgood told Reuters Health by email. "We can, however, conclude that in our prospective study of never-smokers, 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 etiology of lung cancer in the absence of active tobacco smoking."

In a linked editorial, Dr. David Christiani of Harvard University says that despite some limitations, the results are "robust and the observed loss of alpha-diversity, combined with specific taxa abundance may well play a mechanistic role in the genesis of lung cancer in non-smokers."

"There are several postulated mechanisms of carcinogenic action of oral microbes. One is bacterial stimulation of chronic inflammation, which can cause cell proliferation, mutagenesis, oncogene activation and angiogenesis. Another mechanism is that bacteria can affect cell proliferation, cytoskeletal rearrangements, activation of nuclear factor kappa-beta (NF-kB) and inhibition of apoptosis," Dr, Christiani explains.

Questions that remain, he says, include how stable the human oral microbiome is over time; if it varies over time, what determines that variability? And how does the ambient environment such as exposure to air pollutants, affect the oral (and lung) microbiome?

He adds: "It remains unclear whether the oral microbiome as measured in this (and other) epidemiological studies represents a causative agent or only a marker of disease or immune activity. If it is the former, then it will be important to understand whether the oral microbiome actually seeds the lung microbiome and thus acts locally."

Summing up, Dr. Christiani says, "It will be interesting to see more studies of the oral, nasal and lower respiratory tracts in relation to environmental exposures and various lung disorders. The oral cavity and nasopharynx are the foyers to the lung and further understanding of the functional aspects of the microbiome in these compartments will surely help shed light on disease pathogenesis and disease modification."

SOURCE: and Thorax, online December 14, 2020.