Environmental Arsenic (As) exposure causes non-malignant lung diseases such as COPD and bronchiectasis. Both pathologies have been associated with the infectious etiology. Recently, a lung microbiome study provides evidence that a particular bacterial phylum is associated with severe COPD. Based on Dr. Rogelio recio Vega's data, the kids exposed to high arsenic containing drinking water had high incidence of infection. In our preliminary study, As repressed airway major mucin expression both in vivo and in vitro. Because mucociliary clearance is the major airway defense system, we hypothesize that As exposure significantly represses arway mucin expression, thereby altering lung microbiome, which may plan an important role in As-induced lung diseases. Therefore, we propose the following two aims:
- Aim 1. To determine the potential alterations of lung microbiome in the induced sputum samples from the subjects exposed to high and low arsenic containing drinking water. In this aim, we will use cutting edge deep sequencing technology to profile lung microbiome using the existing induces sputum samples collected by Dr. Rogelio Recio Vega. Mucin content in these samples will also be measured.
- Aim 2. To determine the alterations of lung microbiome in the mice exposed to low-dose arsenic-containing drinking water and mucin knockout (KO) mice. In this aim, we will determine if the mouse lung microbiome is affected by the arsenic exposur, and if mucin KO mice have the similar alterations. We will also determine if the potential changes of lung microbiome have any effect on airway inflammation and lung function.
The long-term objective of the present proposal is to elucidate the role of lung microbiome in the pathogenesis of arsenic induced lung diseases. The strengths of this project include: joint expertise in the microbiome, lung biology and animal model of arsenic exposure, ready access to clinical samples, and full utilization of three SWEHSC sponsored cores: Integrated Health Science Facility Core, Cellular Imaging Facility Core, and Genomics Facility Core. Successful completion of this pilot can lead to at least two R01 grants: one for NIEHS focusing on microbiome and the environmental exposure to arsenic, and the other for NLHBI focusing on microbiome and mucin.