Does the level of bacterial exposure in early life impact the risk of Type 1 diabetes?

IntroductionThere is increasing evidence that environmental exposures may be important in the pathogenesis of type 1 diabetes (T1D). Ultraviolet radiation (UVR) is of interest in relation to the development of T1D because of its immunoregulatory actions. Ecological studies testing the correlation between levels of UVR and T1D have shown a significant inverse relationship for both incidence and prevalence. Objectives and Approach We used large linked datasets to test ambient UVR during early life against T1D risk at the individual level. We conducted a nested case-control study using linked data from state-wide administrative datasets and NASA satellites. Cases (n=1819) were all children born in Western Australia from 1980-2014 with a diagnosis of T1D on the population-based Western Australian Children’s Diabetes Database between 0-16 years of age. Controls (n=27 259) were randomly selected from all live births in Western Australia and matched to cases on sex and date of birth. Daily UVR data from NASA satellites, that were date-and location-specific for each individual, were used to estimate total UVR dose for each trimester of pregnancy and the first year of life. ResultsConditional logistic regression showed that T1D risk was 44% lower in boys of mothers with UVR levels in the highest quartile (compared to the lowest quartile) during their third trimester of pregnancy (p=0.04). Higher UVR in the first year of life was also associated with a significantly lower risk of T1D in later childhood among boys. Among girls, there was no evidence of an association between total UVR dose and T1D risk. ConclusionHigher UVR in the third trimester and first year of life appears to interact with sex-specific factors to lower T1D risk among boys (but not girls) in Western Australia.

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Infant anthropometry, early life infection, and subsequent risk of type 1 diabetes mellitus: a prospective birth cohort study

Pediatric Diabetes ◽

10.1111/j.1399-5448.2010.00693.x ◽

2011 ◽

Vol 12 (4pt1) ◽

pp. 313-321 ◽

Cited By ~ 6

Author(s):

Anne-Louise Ponsonby ◽

Angela Pezic ◽

Jennifer Cochrane ◽

Fergus J Cameron ◽

Mark Pascoe ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Cohort Study ◽

Type 1 Diabetes Mellitus ◽

Early Life ◽

Birth Cohort Study ◽

Prospective Birth Cohort ◽

Prospective Birth Cohort Study ◽

Subsequent Risk

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Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

eLife ◽

10.7554/elife.37816 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 25

Author(s):

Xue-Song Zhang ◽

Jackie Li ◽

Kimberly A Krautkramer ◽

Michelle Badri ◽

Thomas Battaglia ◽

...

Keyword(s):

Gene Expression ◽

Type 1 Diabetes ◽

Early Life ◽

System Development ◽

Nod Mice ◽

Intestinal Microbiome ◽

Host Immune System ◽

Intestinal Immunity ◽

Immune System Development

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

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