Early Probiotic Supplementation and the Risk of Celiac Disease in Children at Genetic Risk.

Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk.

Maternal use of dietary supplements during pregnancy is not associated with coeliac disease in the offspring: The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Perinatal exposure to nutrients and dietary components may affect the risk for coeliac disease (CD). We investigated the association between maternal use of vitamin D, n-3 fatty acids (FA) and Fe supplements during pregnancy and risk for CD autoimmunity (CDA) and CD in the offspring. Children at increased genetic risk were prospectively followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. CDA was defined as having persistently positive tissue transglutaminase autoantibodies (tTGA). Diagnosis of CD was either biopsy-confirmed or considered likely if having persistently elevated levels of tTGA>100 AU. Of 6627 enrolled children, 1136 developed CDA at a median 3·1 years of age (range 0·9-10) and 409 developed CD at a median 3·9 years of age (range 1·2-11). Use of supplements containing vitamin D, n-3 FA and Fe was recalled by 66, 17 and 94 % of mothers, respectively, at 3-4 months postpartum. The mean cumulative intake over the entire pregnancy was 2014 µg vitamin D (sd 2045 µg), 111 g n-3 FA (sd 303 g) and 8806 mg Fe (sd 7017 mg). After adjusting for country, child's human leucocyte antigen genotype, sex, family history of CD, any breast-feeding duration and household crowding, Cox's proportional hazard ratios did not suggest a statistically significant association between the intake of vitamin D, n-3 FA or Fe, and risk for CDA or CD. Dietary supplementation during pregnancy may help boost nutrient intake, but it is not likely to modify the risk for the disease in the offspring.

Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study.

IMPORTANCE: Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity. OBJECTIVE: To examine the association between supplemental probiotic use during the first year of life and islet autoimmunity among children at increased genetic risk of T1DM. DESIGN, SETTING, AND PARTICIPANTS: In this ongoing prospective cohort study that started September 1, 2004, children from 6 clinical centers, 3 in the United States (Colorado, Georgia/Florida, and Washington) and 3 in Europe (Finland, Germany, and Sweden), were followed up for T1DM-related autoantibodies. Blood samples were collected every 3 months between 3 and 48 months of age and every 6 months thereafter to determine persistent islet autoimmunity. Details of infant feeding, including probiotic supplementation and infant formula use, were monitored from birth using questionnaires and diaries. We applied time-to-event analysis to study the association between probiotic use and islet autoimmunity, stratifying by country and adjusting for family history of type 1 diabetes, HLA-DR-DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child's antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking. Altogether 8676 infants with an eligible genotype were enrolled in the follow-up study before the age of 4 months. The final sample consisted of 7473 children with the age range of 4 to 10 years (as of October 31, 2014). EXPOSURES: Early intake of probiotics. MAIN OUTCOMES AND MEASURES: Islet autoimmunity revealed by specific islet autoantibodies. RESULTS: Early probiotic supplementation (at the age of 0-27 days) was associated with a decreased risk of islet autoimmunity when compared with probiotic supplementation after 27 days or no probiotic supplementation (hazard ratio [HR], 0.66; 95% CI, 0.46-0.94). The association was accounted for by children with the DR3/4 genotype (HR, 0.40; 95% CI, 0.21-0.74) and was absent among other genotypes (HR, 0.97; 95% CI, 0.62-1.54). CONCLUSIONS AND RELEVANCE: Early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of T1DM. The result needs to be confirmed in further studies before any recommendation of probiotics use is made.

Influence of early nutritional components on the development of murine autoimmune diabetes.

BACKGROUND/AIMS: Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse. METHODS: A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies. RESULTS: A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development. CONCLUSIONS: Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.

The effect of maternal T1DM on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in infants during early life.

BACKGROUND: The risk for type 1 diabetes (T1DM) in children of mothers with T1DM is different to that in children of fathers with T1DM. Fatty acid (FA) intake, in particular EPA and DHA, has been associated with T1DM risk and has been suggested to be inadequate in infants of diabetic mothers. We asked, therefore, whether EPA and DHA FA nutritional status in offspring of mothers with T1DM could contribute to their reduced T1DM risk. METHODS: BABYDIET follows children with increased genetic and familial risk for T1DM from birth to age 3 years. FA nutritional state was assessed by determining the erythrocyte membrane phosphatidylethanolamine (PE) and phosphatidylcholine (PC) composition in children of T1DM mothers and children of T1DM fathers or with T1DM siblings participating in the BABYDIET study. Samples for determination of erythrocyte membrane FA composition were collected at ages 3 and 12 months in 48 and 49 infants, respectively. FA measurements were adjusted for breastfeeding duration, FA supplementation, and gluten exposure. RESULTS: 3-months-old children of T1DM mothers and T1DM fathers/sibs had similar levels of PC DHA and EPA (DHA 1.53+/-0.23 vs. 1.65+/-0.11 wt.%; EPA 0.15+/-0.02 vs. 0.21+/-0.03 wt.%) and PE DHA and EPA (DHA 7.54+/-0.37 vs. 7.92+/-0.38 wt.%; EPA 0.53+/-0.06 vs. 0.61+/-0.04 wt.%). No differences were also observed after stratification for breastfeeding. At age 12 months, a minor reduction of PE DHA was observed in children of T1DM mothers. Expected higher levels for DHA and EPA in fully breastfed children and in children of mothers taking fish oil supplementation were observed at 3 months in all children. Other differences included increased levels of the major saturated FA 16:0 in 3-months-old infants from T1DM mothers (PC 35.45+/-0.35 vs. 33.89+/-0.26 wt.%, mean +/- SEM, P(corr)=0.005; PE 16.13+/-0.39 vs. 14.93+/-0.24 wt.%, P(corr)=0.05). CONCLUSION: Although FA status was not identical in children from T1DM mothers and from T1DM fathers, maternal T1DM was not associated with changes in offspring's EPA and DHA incorporation into erythrocyte membrane.

Delayed exposure to wheat and barley proteins reduces diabetes incidence in non-obese diabetic mice.

Dietary gluten, vitamin D3, and fish-oil are suggested to influence the incidence of autoimmune diabetes. To determine whether modification of their intake could reduce diabetes incidence and autoimmunity in mice, pups from female non-obese diabetic (NOD) mice were fed diets modified for protein source, fatty acid content, and/or vitamin D3 content and were followed for diabetes development, insulin autoantibodies (IAA), and insulitis. Replacement of wheat and barley with poultry as the major protein source significantly affected diabetes development. Diabetes onset was delayed and diabetes incidence was significantly reduced in female mice that received the wheat and barley protein-free diet throughout life (45% by age 32 weeks vs. 88% in control mice; P < 0.01), from weaning (42%; P < 0.005), or from 3 to 10 weeks of age only (36%; P < 0.01), and diabetes development was not completely restored by gliadin supplementation of the wheat and barley protein-free diet (58%; P < 0.05). Insulin autoantibodies (P < 0.01) and insulitis scores (P < 0.02) were reduced, and intra-pancreatic IL-4 mRNA increased (P < 0.05) in wheat and barley protein-deprived mice. Diabetes incidence was neither reduced by fish-oil or vitamin D3 supplementation alone, nor in mice fed a wheat and barley protein-free diet that was supplemented with fish-oil and vitamin D3. These data support a link between dietary wheat and barley proteins and the development of autoimmune diabetes.