The Hygiene Hypothesis and Type 1 Diabetes Mellitus

An agroforestry area

D.P. Strachan in 1958 proposed an idea called the “hygiene hypothesis.” The theory is that infections and exposure to microbes (germs) in early life decreases the incidence of allergic and autoimmune diseases such as type 1 diabetes, asthma, and atopic dermatitis. Autoimmune and allergic diseases seem to be on the rise for more than a half-century, perhaps related to our urbanized lifestyles that have taken us away from the germ-rich environment of farms and forests. And we do our best to sterilize our homes with antimicrobial soaps, countertop cleaners, and hand sanitizers that we didn’t use even 20 years ago.

Exactly how early-life exposure to infections and germs could lead to autoimmune and allergic diseases is beyond the scope of today’s post. I’ll just say that germ exposure may help teach our immune system to better regulate itself. In case you don’t know, the immune system plays a large role in allergic diseases and symptoms.

A recent study out of Finland supports the hygiene hypothesis and was published in Diabetes Care:

OBJECTIVE 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 to evaluate the role of environmental microbial biodiversity in the pathogenesis.

RESEARCH DESIGN AND METHODS Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease-associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies.

RESULTS Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16–0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity.

CONCLUSIONS The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry 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.

From the introduction:

“The incidence of type 1 diabetes has increased during the past 70 years in the developed countries paralleling similar increase in other immune-mediated diseases such as allergies and asthma. The rapid increase, together with the conspicuous variation in incidence rates between countries, supports the role of environmental factors in the pathogenesis. Overall, the incidence rate tends to be high in countries located in the north, although exceptions to this trend exist.

“Living in an agricultural environment and contacts with farm animals and pets at home has been associated with a higher microbial diversity indoors and a decreased risk of allergic diseases. Although the mechanisms of this phenomenon are not fully understood, several lines of evidence suggest that exposure to environmental microbial diversity and direct soil contacts may play a role. This, in turn, could lead to the activation of immunoregulatory pathways suppressing overreactive immune responses, as presented by the biodiversity hypothesis. A wide exposure of the skin and mucosal surfaces to all kinds of microbes, including bacteria, viruses, and eukaryotes, regardless of whether they are infecting or colonizing humans, could provide constant immunological stimulation to the immune system, which is needed for the development of healthy immune regulation.

“As with allergic diseases, type 1 diabetes is also associated with failure to control hyperreactive immune responses. In type 1 diabetes, these immune responses target β-cell autoantigens instead of allergens.” 

Steve Parker, M.D.

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