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Grant: Project Grant

University of Victoria (British Columbia)

$1,082,476.00

Environmental factors and mechanisms influencing oral tolerance to dietary antigens during early life

FY 2025-26

Summary
Food allergies are becoming increasingly common, and to stop the rise in new cases we need to better understand the factors that prevent, or contribute, to food allergy development. Evidence from large studies of human infants now suggests that early oral introduction of potentially problematic foods such as eggs and peanuts (as opposed to avoiding these foods) is protective against developing an allergy against these foods later in life. We know that in healthy individuals (who do not have food allergies), a process occurs called "oral tolerance"- where the immune system actively learns which food substances it should not inappropriately react to. There has been a lot of previous work to identify the immune cell types involved in oral tolerance development from experimental studies in mice, however, most of this knowledge comes from studies of adult mice, not from young mice that are still suckling milk. The immune system functions differently in young animals as it is still developing, and exposure to breastmilk impacts cell types involved in oral tolerance. For these reasons we plan to study how oral tolerance develops in young mice, as we think this will give us the best insight into the mechanisms helping to prevent food allergy develop in infants who are being exposed to solid foods for the first time. Pregnant females in North America are commonly given antibiotics prior to and during labour, for various reasons. While this antibiotic treatment is effective at preventing transmission of potentially dangerous bacteria to the infant during birth, it has unintended consequences in that it changes the types of gut bacteria in the infant over the first year of life. Whether this type of early life antibiotic exposure influences the infant's ability to develop oral tolerance to food substances in early life has not yet been investigated, and we plan on using a mouse model to address this question.
Program
Project Grant
Location
British Columbia, Canada
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
564904
Name
Reynolds Lisa A
Region
British Columbia
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Infection and Immunity
Theme2
Biomedical
Prcname2
Immunology
Projecttitle
Environmental factors and mechanisms influencing oral tolerance to dietary antigens during early life
Programtype2
Operating Grants
Orgnameinp2
University of Victoria (British Columbia)
Cihramount2
$1,082,476
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Adoptive Cell Transfer; Cd4 T Cells; Dietary Antigens; Early Postnatal Life Immunology; Flow Cytometry; Intrapartum Antibiotic Exposure; Metabolites; Microbiome; Mouse Models; Oral Tolerance
Abstract
Food allergies are becoming increasingly common, and to stop the rise in new cases we need to better understand the factors that prevent, or contribute, to food allergy development. Evidence from large studies of human infants now suggests that early oral introduction of potentially problematic foods such as eggs and peanuts (as opposed to avoiding these foods) is protective against developing an allergy against these foods later in life. We know that in healthy individuals (who do not have food allergies), a process occurs called "oral tolerance"- where the immune system actively learns which food substances it should not inappropriately react to. There has been a lot of previous work to identify the immune cell types involved in oral tolerance development from experimental studies in mice, however, most of this knowledge comes from studies of adult mice, not from young mice that are still suckling milk. The immune system functions differently in young animals as it is still developing, and exposure to breastmilk impacts cell types involved in oral tolerance. For these reasons we plan to study how oral tolerance develops in young mice, as we think this will give us the best insight into the mechanisms helping to prevent food allergy develop in infants who are being exposed to solid foods for the first time. Pregnant females in North America are commonly given antibiotics prior to and during labour, for various reasons. While this antibiotic treatment is effective at preventing transmission of potentially dangerous bacteria to the infant during birth, it has unintended consequences in that it changes the types of gut bacteria in the infant over the first year of life. Whether this type of early life antibiotic exposure influences the infant's ability to develop oral tolerance to food substances in early life has not yet been investigated, and we plan on using a mouse model to address this question.
Competitiondate
202603
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Reynolds, Lisa A
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $1,082,476~ $0~