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Title [sv]
Tidiga miljöfaktorer, tarmfloran och typ-1 diabetes
Title [en]
Early life exposures: the microbiome and type 1 diabetes
Abstract [en]
The incidence of type 1 diabetes has doubled in the last 30 years in Sweden, most likely because of a concomitant increase in one or several as yet unidentified environmental causes. The ‚Äúhygiene hypothesis‚Äù proposes that the increase in immune-related disorders is causally related to the depletion of microorganisms in the home environment and that these microorganisms normally have a crucial role in establishing normal immune regulation. In accordance with the hygiene hypothesis, a higher exposure to microbes, indicated for example by a higher number of siblings, decreases the risk of immune-related disease in childhood, including type 1 diabetes. While studies of the hygiene hypothesis initially focused on overall infectious exposures in early childhood, there has been more recent recognition of a specific role of commensal bacteria in early infancy. Several animal studies indicate that alterations in the intestinal microbiota are associated with the development of autoimmune disease such as type 1 diabetes through an overly activated immune system. A specific role of the microbiome in human type 1 diabetes development has been supported by the finding that the faecal microbiota composition was found to differ between non-diabetic children with Œ≤-cell autoimmunity and those without. The overarching aim of the proposed research program is to test the hypothesis that an early exposure to factors that modifies the microbiome in infancy also affects type 1 diabetes risk. The specific aims of this project are: 1. To elucidate the impact of early life animal exposure and antibiotic treatment on the diversity and functionality of the gut flora of the infant.Recent advances in sequencing techniques have enabled large-scale studies of the human microbiome, i.e. the population of microorganisms living in association with the body. We propose to assess the impact of early life exposures on microbiota diversity and function using repeated faecal samples and detailed phenotypic data from 80 mother-child pairs within the Lifegene: Born into Life cohort and 500 mother-child-(pet) pairs/triplets from the planned study FLORA. These studies will advance the knowledge about the impact of common early life exposures on the microbial ecosystem diversity and function allowing detailed follow-up analysis of disease events.2. To determine whether animal exposure and antibiotic treatment during pregnancy and the first year of life is associated with modified risk of type 1 diabetesAntibiotic treatment and animal exposure are common during pregnancy and in infants, but the impact on type 1 diabetes risk is not clear. We propose to analyse the data from a nation-wide cohort including all children born in Sweden between 2001 and 2011 to assess the risk of type 1 diabetes in relation to exposure to antibiotics, dogs, and farm animals including a sibling-design to account for familial confounding factors. With the large prospective study sample and the detailed data on prescriptions and animal exposure, we will be able to estimate the impact of these factors on the risk of type 1 diabetes. These studies will yield important information on the impact of antibiotic treatment and animal exposure on the diversity and function of the human microbial ecosystem and type 1 diabetes risk. New knowledge in this field could help in making well-informed decisions of antibiotic therapy in pregnant women and infants and also guide families in the appropriateness and timing of animal exposures. More important - if our hypothesis holds true, it would open up new avenues for intervention studies aiming at enriching the infant´s microbiome in order to decrease risk of type 1 diabetes.
Principal InvestigatorFall, Tove
Coordinating organisation
Uppsala University
Funder
Period
2016-01-01 － 2019-12-31
National Category
Endocrinology and DiabetesPublic Health, Global Health, Social Medicine and Epidemiology
Identifiers
DiVA, id: project:5571Project, id: 2015-03477_VR
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