Impact of the Microbiota on Immune Development and Disease

Project Information

Project Title:

Impact of the Microbiota on Immune Development and Disease

Principal Investigator(s):

Finlay, Barton B; McNagny, Kelly M; Mohn, William W

Co-Investigators:

Kollmann, Tobias R; Moore, Richard; O’Doherty, Kieran C; Turvey, Stuart E

Institution Paid:

University of British Columbia

Research Institution:

University of British Columbia 

Department:

Michael Smith Laboratories

Program:

Emerging Team Grant: Canadian Microbiome Initiative – Full Application

Competition(Year/Month):

201005 

Assigned Peer Review Committee:

CMF Emerging Team Grant: Canadian Microbiome Initiative

Primary Institute:

Infection and Immunity 

Primary Theme:

Biomedical 

Term (Yrs/Mths):

5 yrs 0 mth  

CIHR Contribution:

External Funding Partner(s):

Keywords:

16S RRNA; ANTIBIOTICS; ASTHMA; ATOPIC DISEASES; COHORT STUDY; IMMUNE DEVELOPMENT; MICROBIOTA; NORMAL FLORA; TH1/TH2; WHEEZING

Abstract:

There is increasing evidence that intestinal microbiota impact on immune development and disease. Allergic asthma is an ever-increasing problem in developed countries and affects up to 20% of all Canadians. Although there are many theories about the potential cause of asthma, the actual causes remain undefined. Recent evidence suggests that shifts in resident microbiota (normal flora) may play a significant role in atopic diseases such as asthma (the so-called hygiene hypothesis. However, the role of the gastrointestinal microbiota in asthma has not been explored experimentally, and no attempt has been made to identify microbial populations affecting asthma. We propose to assemble a strong interdisciplinary team to explore the contribution of the microbiota to immune development and the atopic disease asthma in both murine and human hosts. We will employ a well-characterized murine model of asthma to determine how the microbiota affects this disease by varying the microbiota using different antibiotics. The murine immune responses will be monitored following these microbiota shifts. Moreover, as part of the CHILD longitudinal cohort study, immune analysis will be performed on samples taken from children from birth until 1 year of age. In correlation with these studies, the composition of the intestinal microbiota will be characterized, and correlated with atopic diseases, as well results from the murine studies. Applied ethical questions associated with these results will also be studied. Collectively, these approaches will provide key information about the role of the intestinal microbiota in immune development and atopic diseases such as asthma. It will also bring together investigators with very different skills all working on a common problem. Ultimately this information could be used to develop new ways of treating asthma.