Microbial Buffer? The Human Lung Microbiome and Immune Responses to Diesel Exhaust

Short abstract

Having a more diverse lung microbiome was associated better lung capacity and lower measures of airway inflammation among a small group of volunteers exposed to diesel exhaust—even in those with COPD.

The impact of air pollutants and other environmental exposures on the human microbiome is well documented.^1,2 A Research Letter recently published in Environmental Health Perspectives³ suggests that the microbiome may also modify the body’s response to traffic-related air pollution, also called TRAP.

The researchers conducted a unique controlled exposure study to examine how the human airway microbiome—the multispecies microbial community that dwells in the respiratory tract—reacts to TRAP. They recruited 25 participants to inhale filtered air or diesel exhaust (a model for TRAP) from an electric generator in an exposure booth for two hours. All participants had both exposures, separated by at least four weeks, and were randomly assigned the order of their exposures. Twenty-four hours after each exposure session, the researchers collected tissue samples from the participants' airways with bronchial brushes, and fluid samples with a washing called bronchoalveolar lavage.

The researchers fitted a bronchoscope, similar to the silver device shown here inside a bronchial tube, with a brush to obtain microbiome samples from the lower airways of participants. They also collected lavage fluid. Image: © Carol and Mike Werner/Science Source.

After each exposure, the researchers also measured lung function as the forced expiratory volume (or amount of air the participant could exhale in one second) and converted this to the percent of volume predicted for their age and sex. They analyzed the sampled tissue for a panel of cytokines to measure the immune system's response to the inhaled air. In addition, the team calculated the lung microbiome’s richness, or the number of species of bacteria present. Statistical analyses showed that after breathing diesel exhaust, participants who had less bacterial richness had a significantly greater increase in levels of three cytokines—interleukin-6 (IL-6), IL-7, and IL-15—compared with participants who had greater bacterial richness. IL-6 is among the most consistently identified cytokines associated with air pollution–related inflammatory processes.⁴ The group with less bacterial richness also had a significantly larger reduction in their lung function after diesel exhaust exposure compared with those who had greater richness.

The study participants (45–80 years of age, 37% female)—who self-reported as never- or ex-smokers—ranged from those with normal lung function to those with mild or moderate chronic obstructive pulmonary disease (COPD). Recruiting participants representing a range of lung function was a specific goal of Chris Carlsten, the study’s senior author and a professor of medicine at the University of British Columbia (UBC) in Vancouver, Canada.

“This is a hallmark of the study [and] distinguishes it from previous work,” says Carlsten. “The most commonly studied people in crossover designs are healthy, even though much of the community concern about air pollution is for susceptible populations based on age or existing health conditions.”

Carlsten, left, holds several positions at UBC, including director of the Centre for Lung Health and of the Air Pollution Exposure Laboratory. The study’s first author, Min Hyung Ryu, right, conducted the research while a PhD student at UBC. He is now a postdoctoral fellow at Channing Division of Network Medicine at Brigham and Women’s Hospital and Harvard Medical School. Images: Courtesy of Kevin Lau.

The researchers calculated several summary metrics of microbial richness, including one called the number of amplicon sequence variants (ASVs).⁵ This focus on ASVs was of particular interest to Yvonne Huang, an associate professor of pulmonary and critical care medicine and of microbiology and immunology at the University of Michigan. “ASVs are a newer approach to identifying bacteria from this type of sequencing data,” says Huang, who was not involved in the study.

The findings suggest the possibility that a more diverse airway microbiome may offer some protection against the harmful effects of inhaled pollutants. This is consistent with recent reports that a more diverse microbiome was associated with greater improvement in lung function among people with COPD.⁶

James Gern, a professor of allergy, immunology, and rheumatology at the University of Wisconsin School of Medicine and Public Health, who also was not involved in the study, notes that it remains to be seen whether the observed changes in lung function are of clinical significance. “This is a terrific first-of-its-kind study because it used an exposure chamber and collected lower-airway samples,” says Gern. “Those two features go beyond what's been done before, but more work is needed to determine if the observed changes in IL-6 levels and [the measure of lung function] are clinically meaningful.”

The study did not identify which microbes might contribute to the potential role of the lung microbiome as a buffer. Whether the microbial composition can be modified with dietary or other interventions is a research topic of great interest.⁷ Dietary fiber consumption reduced markers of lung inflammation in mouse models of asthma,^8,9 but associations between diet and the airway microbiome have rarely been examined in humans.⁷

The gut microbiome, on the other hand, has been studied extensively and found to interact with our immune system in multiple ways.¹⁰ Links between the gut and airway microbiomes—the so-called gut–lung axis^11,12—and between gut health and air pollution have been reported, including increased risk of gut diseases in humans exposed to inhaled pollutants.^13,14 “This is why we would like to study next if the diversity of the gut microbiome, as measured in stool samples, affects our response to air pollution,” says Carlsten.

There is also growing interest¹⁵ in a third kind of sample: nasal secretions collected with swabs or brushes for analysis of the nasal microbiome. “This is much less invasive than [using] a bronchoscope for lower-airway sampling,” says Huang. “Studies with multiple sample types from the same person would help us understand how microbial communities in distinct compartments along the respiratory tract respond to air pollution.”

Biography

Silke Schmidt, PhD, writes about science, health, and the environment from Madison, Wisconsin.