Ambient particle pollution, which can be a trigger for myocardial infarction, has been estimated to be the 13th leading cause of premature death and one of the top ten contributors to the global burden of disease world- wide. Despite evidence that ambient particles carry variable amounts of the gram-negative bacterial component endotoxin, the contribution of microbial communities on pollution particles to their inflammatory and cardiovascular effects is poorly defined. Studies suggest that the warm season is lengthening in North America with climate influences on patterns of airborne microbes. We have published and preliminary data demonstrating associations of the endotoxin component of concentrated ambient particles (CAPs) with increased systemic inflammation, oxidative stress and blood pressure in our completed randomized cross-over controlled human exposure study of 55 Toronto adults. Up to forty-percent of the increase in leukocyte count attributed to particle mass could be attributed to its endotoxin content. Endotoxin may be a sentinel marker for a complex array of microbial exposures with other pathogen-associated-molecular patterns (PAMPs) that stimulate human innate immune inflammation potentially relevant to cardiovascular outcomes. Leveraging on our Toronto study, we will combine 16S,18S, ITS rRNA gene and selective whole genome shotgun sequencing with innovative bioinformatic methods to characterize the bacterial and fungal communities on coarse, fine and ultrafine CAP exposures, at the phylum and genus level (Aim 1). We will evaluate how the relative abundance of microbial taxa on CAPS is influenced by ambient temperature and humidity levels in the two weeks prior to testing (Aim 4). We will test the hypothesis that increased abundance of gram-negative phylum Proteobacteria on CAPs will be associated with increased blood pressure, brachial artery narrowing and, secondarily, with increases in intermediate biomarkers of vascular stimulation(vascular endothelial growth factor), systemic inflammation (e.g., white blood cell count), and oxidative stress (e.g., 8-hydroxy-deoxy-guanosine), and will assess the relative contribution of individual bacterial genera within Proteobacteria to these associations (Aim 2). We will evaluate whether the most abundant fungal taxa on CAPs are independently associated with our outcomes (Aim 3). Finally, we will apply bioinformatic methods to our metagenomic data to quantify the relative abundance of synthesis pathways for active components of PAMPS, and explore how pathway abundance influences blood pressure, inflammation and oxidative stress. Understanding the microbial contributions to particle toxicity will help define mechanisms whereby particle pollution increases cardiovascular risk, and will inform regulators estimating the benefits of controlling particle pollution to improve cardiovascular health.

Public Health Relevance

Particle pollution increases systemic inflammation and worsens heart health. With in-chamber filter samples and data from a completed controlled human exposure study, we plan to use innovative methods to define the contribution of bacteria and fungi on pollution particles to increases in subclinical responses relevant to heart health, including blood pressure and inflammation. If microbes on outdoor pollution particles increase their toxicity, then improved health may result from reduction of levels of those particles and the microbes that they carry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21ES024804-01
Application #
8805972
Study Section
Special Emphasis Panel (ZRG1-DKUS-C (90))
Program Officer
Nadadur, Srikanth
Project Start
2015-01-15
Project End
2016-12-31
Budget Start
2015-01-15
Budget End
2015-12-31
Support Year
1
Fiscal Year
2015
Total Cost
$262,188
Indirect Cost
$88,709
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Hanson, Blake; Zhou, Yanjiao; Bautista, Eddy J et al. (2016) Characterization of the bacterial and fungal microbiome in indoor dust and outdoor air samples: a pilot study. Environ Sci Process Impacts 18:713-24