Chronic rhinosinusitis (CRS) is one of the most common diseases for which people visit a health care provider and receive antibiotics. Recent studies have reported that veterans deployed to the Iraq or Afghan theaters of operation are twice as likely to develop upper respiratory disorders. Veterans of OEF/OIF presenting with post deployment onset of rhinosinusitis undisputedly recount that their symptoms were initiated within several weeks of being deployed supporting an environmental contribution. While bacteria in the sinonasal cavity contribute to the pathophysiology, one puzzle is how microbial species that are more common in people with this disease are also constituents of the normal sinonasal microbiota of healthy people. These phenotypic differences may be due to the inborn genetics of the human host, specifically variation in the taste receptor gene family that are accentuated with exposure to varied environments. Some of these bitter taste receptors, in addition to detecting chemicals on the tongue (taste), also detect secreted bacterial chemicals and trigger the ciliated cells of the sinonasal epithelium to launch an attack. One by-product of this particular physiological system is that people who are not able to taste certain types of bitter compounds may be less able to fight certain bacteria with the same weak sensory signaling pathway. The goal of the proposed research is to combine the expertise of three laboratories to test whether there are interactions between genetic variation of the human host, individual nasal microbiota, and the development of chronic rhinosinusitis: (1) A surgeon scientist with expertise in the medical and surgical treatment of individuals with CRS with access to patients with and without exposure to a foreign environment will ascertain and evaluate the patients. (2) A genomics expert will quantify the human microbiome to the species level using new technologies. (3) A human geneticist and her team will genotype human genomic DNA and evaluate subjects for their ability to taste bitter compounds. The hypothesis is that people with different inborn differences in their ability to detect the chemicals secreted by bacteria will have a different microbiome patterns and susceptibility to CRS. To that end, we will evaluate 60 patients with CRS (cases) and 60 age-, sex, and race-matched healthy controls. This ?bitterome? research could explain, at least in part, how bacterial virulence arises in specific individuals and perhaps lead to simple clinical tests to determine how best to personalize treatment.

Public Health Relevance

We discovered an unexpected role for taste receptors in the human nose: they detect and respond to the chemical signals produced by bacteria. In this project we will test the idea that people with inborn differences in taste receptor function have different microbial signatures and different susceptibilities to chronic rhinosinusitis. This ?bitterome? research could explain, at least in part, how bacterial virulence arises in specific individuals and perhaps how best to personalize treatment.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01CX001617-02
Application #
9652667
Study Section
Infectious Diseases B (INFB)
Project Start
2017-10-01
Project End
2021-09-30
Budget Start
2018-10-01
Budget End
2019-09-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Philadelphia VA Medical Center
Department
Type
DUNS #
071609291
City
Philadelphia
State
PA
Country
United States
Zip Code
19104