posted on 2021-05-05, 18:35authored byNoora Nurminen, Damiano Cerrone, Jussi Lehtonen, Anirudra Parajuli, Marja Roslund, Maria Lönnrot, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Mikael Knip, Juho Rajaniemi, Olli H. Laitinen, Aki Sinkkonen, Heikki Hyöty
OBJECTIVE
<div><p>Environmental microbial
exposures have been implicated to protect against immune-mediated diseases such
as type 1 diabetes. Our objective was
to study the association of land cover
around the early-life dwelling with the development of islet autoimmunity and
type 1 diabetes in order to evaluate the role of environmental microbial biodiversity
in the pathogenesis.</p>
<p>RESEARCH DESIGN AND METHODS</p>
<p>Association between land
cover types and the future risk of type 1 diabetes was studied by analyzing
land cover types classified according to CORINE 2012 and 2000 data around the
dwelling during the first year of life for<a> </a><a></a><a>10681</a> children genotyped for disease associated HLA-DQ
alleles and followed from birth in the DIPP study. Land cover was compared
between children who developed type 1 diabetes (N=271) or multiple
diabetes-associated islet autoantibodies (N=384) and non-diabetic autoantibody
negative children.</p>
<p>RESULTS</p>
<p>Agricultural land cover <a>around the home </a>was inversely associated with diabetes
risk (OR 0.37, 95% CI 0.16-0.87, <i>P =</i> 0.02 <a>within a
distance of 1500 m</a>). The association was observed among children with the
high-risk HLA-genotype and among those living in the southernmost study region.
<a>Snow cover on the ground seemed to block the transfer of
microbial community indoors leading to reduced bacterial richness and diversity
indoors which might explain the regional difference in the association. </a>In
survival models, agricultural environment was associated with a decreased risk
of multiple islet autoantibodies (HR=1.60, <i>P =</i> 0.008) and a decreased
risk of progression from single to multiple autoantibody positivity (HR=2.07, <i>P
=</i> 0.001) compared to urban environment known to have lower environmental microbial
diversity.</p>
<p>CONCLUSIONS</p>
<p>The study suggests that
exposure to agricultural environment (comprising non-irrigated arable land, fruit
trees and berry plantations, pastures, natural pastures, land principally
occupied by agriculture with significant areas of natural vegetation, and agro-forestry
areas) early in life is inversely associated with the risk of type 1 diabetes.
This association may be mediated by early exposure to environmental microbial diversity.</p></div>
Funding
This work is supported by the Finnish Funding Agency for Innovation TEKES under the Large Strategic Opening project ‘ADELE’ (grant number 40333/14) and HiLIFE Proof of Concept grant. This work and the DIPP study is additionally supported by JDRF (grants 1-SRA-2016-342-M-R, 1-SRA-2019-732-M-B); Novo Nordisk Foundation; Academy of Finland (Decision No 292538 and Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017, Decision No. 250114); Special Research Funds for University Hospitals in Finland; Sigrid Juselius Foundation and the Diabetes Research Foundation in Finland.