Birth weight in newborn infants with different diabetes‐associated HLA genotypes in three neighbouring countries: Finland, Estonia and Russian Karelia

Peet, Aleksandr; Kool, Pille; Ilonen, Jorma; Knip, Mikael; Tillmann, Vallo

doi:10.1002/dmrr.2303

Cited by 23 publications

(23 citation statements)

References 37 publications

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“…The infants were followed from birth to three years of age by monthly stool sampling along with collection of extensive clinical metadata. The cohort thus provides the largest longitudinal functional profile of the infant gut microbiome in relation to immune-mediated diseases to date, representing an unprecedented opportunity to understand the microbial ecology and molecular mechanisms potentially underlying the hygiene hypothesis (Peet et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Vatanen

Kostic

d’Hennezel

et al. 2016

Cell

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Summary According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore their Lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.

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Section: Introductionmentioning

confidence: 99%

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Vatanen

Kostic

d’Hennezel

et al. 2016

Cell

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1,036

808

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“…Prospective studies have followed infants and children with high‐risk HLA haplotypes to identify early life risk factors . Islet‐specific autoimmunity is marked by multiple anti‐islet autoantibodies (AAb) that are strongly predictive of disease progression .…”

Section: The Gut Microbiome In T1dmentioning

confidence: 99%

Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome

Paun

Danska

2016

Pediatr Diabetes

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The prevalence of type 1 and type 2 diabetes have both risen dramatically over the last 50 years. Recent findings point towards the gut microbiota as a potential contributor to these trends. The hundred trillion bacteria residing in the mammalian gut have established a symbiotic relation with their host and influence many aspects of host metabolism, physiology, and immunity. In this review, we examine recent data linking gut microbiome composition and function to anti-pancreatic immunity, insulin-resistance, and obesity. Studies in rodents and human longitudinal studies suggest that an altered gut microbiome characterized by lower diversity and resilience is associated with type 1 and type 2 diabetes. Through its metabolites and enzymatic arsenal, the microbiota shape host metabolism, energy extracted from the diet and contribute to the normal development of the immune system and to tissue inflammation. Increasing evidence underscores the importance of the maternal microbiome, the gestational environment and the conditions of newborn delivery in establishing the gut microbiota of the offspring. Perturbations of the maternal microbiome during gestation, or that of the offspring during early infant development may promote a pro-inflammatory environment conducive to the development of autoimmunity and metabolic disturbance. Collectively the findings reviewed herein underscore the need for mechanistic investigations in rodent models and in human studies to better define the relationships between microbial and host inflammatory activity in diabetes, and to evaluate the potential of microbe-derived therapeutics in the prevention and treatment of both forms of diabetes.

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“…Altogether we studied 159 children: 28 Finnish children with type 1 diabetes, 90 children (57 Finnish and 33 Estonian children) from the DIABIMMUNE study (18), and 41 children from the Finnish Type 1 Diabetes Prediction and Prevention study (19 Nine of the 29 children (31%) with early b cell autoimmunity had one autoantibody at the study visit, 7 children (24%) tested positive for two autoantibodies, 6 children (21%) were positive for three autoantibodies, and 7 children were positive for four autoantibodies. One of nine children with advanced b cell autoimmunity and IGT tested positive for one biochemical autoantibody (11%), two children were positive for two autoantibodies (22%), four children were positive for three autoantibodies (44%), and two children were positive for four biochemical autoantibodies (22%) at the time of assessing the activation of Th17 immunity.…”

Section: Study Subjectsmentioning

confidence: 99%

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

Reinert-Hartwall¹,

Honkanen²,

Salo³

et al. 2015

The Journal of Immunology

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Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions.

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Birth weight in newborn infants with different diabetes‐associated HLA genotypes in three neighbouring countries: Finland, Estonia and Russian Karelia

Abstract: The previously reported association between HLA-risk haplotypes for T1D and an increased birth weight was not confirmed. This suggests that the mechanisms behind the association between high birth weight and risk for T1D may be not directly HLA related.

Cited by 23 publications

References 37 publications

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

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