Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study.

PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years. METHODS: We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country. RESULTS: A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D.  CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.

Detecting potential outliers in longitudinal data with time-dependent covariates.

BACKGROUND: Outliers can influence regression model parameters and change the direction of the estimated effect, over-estimating or under-estimating the strength of the association between a response variable and an exposure of interest. Identifying visit-level outliers from longitudinal data with continuous time-dependent covariates is important when the distribution of such variable is highly skewed. OBJECTIVES: The primary objective was to identify potential outliers at follow-up visits using interquartile range (IQR) statistic and assess their influence on estimated Cox regression parameters. METHODS: Study was motivated by a large TEDDY dietary longitudinal and time-to-event data with a continuous time-varying vitamin B12 intake as the exposure of interest and development of Islet Autoimmunity (IA) as the response variable. An IQR algorithm was applied to the TEDDY dataset to detect potential outliers at each visit. To assess the impact of detected outliers, data were analyzed using the extended time-dependent Cox model with robust sandwich estimator. Partial residual diagnostic plots were examined for highly influential outliers. RESULTS: Extreme vitamin B12 observations that were cases of IA had a stronger influence on the Cox regression model than non-cases. Identified outliers changed the direction of hazard ratios, standard errors, or the strength of association with the risk of developing IA. CONCLUSION: At the exploratory data analysis stage, the IQR algorithm can be used as a data quality control tool to identify potential outliers at the visit level, which can be further investigated.

Fruit, berry, and vegetable consumption and the risk of islet autoimmunity and type 1 diabetes in children-the Type 1 Diabetes Prediction and Prevention birth cohort study.

BACKGROUND: Prospective studies investigating the association among fruit, berry, and vegetable consumption and the risk of islet autoimmunity (IA) and type 1 diabetes (T1D) are few. OBJECTIVES: In this cohort study, we explored whether the consumption of fruits, berries, and vegetables is associated with the IA and T1D development in genetically susceptible children. METHODS: Food consumption data in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) cohort study were available from 5674 children born between September 1996 and September 2004 in the Oulu and Tampere University Hospitals. Diet was assessed with 3-d food records at the age of 3 and 6 mo and annually from 1 to 6 y. The association between food consumption and the risk of IA and T1D was analyzed using joint models adjusted for energy intake, sex, human leukocyte antigen (HLA) genotype, and a family history of diabetes. RESULTS: During the 6-y follow-up, 247 children (4.4%) developed IA and 94 (1.7%) T1D. Furthermore, 64 of 505 children with at least 1 repeatedly positive autoantibody (12.7%) progressed from islet autoantibody positivity to T1D. The consumption of cruciferous vegetables was associated with decreased risk of IA [hazard ratio (HR): 0.83; 95% credible intervals (CI): 0.72, 0.95, per 1 g/MJ increase in consumption] and the consumption of berries with decreased risk of T1D (0.60; 0.47, 0.89). The consumption of banana was associated with increased risk of IA (1.08; 1.04, 1.12) and T1D (1.11; 1.01, 1.21). Only the association between banana and IA remain significant after multiple testing correction. CONCLUSIONS: In children genetically at risk for T1D, the consumption of cruciferous vegetables was associated with decreased risk of IA and consumption of berries with decreased risk of T1D. In addition, the consumption of banana was associated with increased risk of IA and T1D.

Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk.

BACKGROUND: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence. OBJECTIVES: This study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children. METHODS: Data was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake. RESULTS: At age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03). CONCLUSIONS: Dietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.

The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut.

Diversity of the gut microbiota is crucial for human health. However, whether fruit and vegetable associated bacteria contribute to overall gut bacterial diversity is still unknown. We reconstructed metagenome-assembled genomes from 156 fruit and vegetable metagenomes to investigate the prevalence of associated bacteria in 2,426 publicly available gut metagenomes. The microbiomes of fresh fruits and vegetables and the human gut are represented by members in common such as Enterobacterales, Burkholderiales, and Lactobacillales. Exposure to bacteria via fruit and vegetable consumption potentially has a beneficial impact on the functional diversity of gut microbiota particularly due to the presence of putative health-promoting genes for the production of vitamin and short-chain fatty acids. In the human gut, they were consistently present, although at a low abundance, approx. 2.2%. Host age, vegetable consumption frequency, and the diversity of plants consumed were drivers favoring a higher proportion. Overall, these results provide one of the primary links between the human microbiome and the environmental microbiome. This study revealed evidence that fruit and vegetable-derived microbes could be found in the human gut and contribute to gut microbiome diversity.

Fatty acid-mediated signaling as a target for developing type 1 diabetes therapies.

INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease in which pro-inflammatory and cytotoxic signaling drive the death of the insulin-producing ß cells. This complex signaling is regulated in part by fatty acids and their bioproducts, making them excellent therapeutic targets. AREAS COVERED: We provide an overview of the fatty acid actions on ß cells by discussing how they can cause lipotoxicity or regulate inflammatory response during insulitis. We also discuss how diet can affect the availability of fatty acids and disease development. Finally, we discuss development avenues that need further exploration. EXPERT OPINION: Fatty acids, such as hydroxyl fatty acids, ω-3 fatty acids, and their downstream products, are druggable candidates that promote protective signaling. Inhibitors and antagonists of enzymes and receptors of arachidonic acid and free fatty acids, along with their derived metabolites, which cause pro-inflammatory and cytotoxic responses, have the potential to be developed as therapeutic targets also. Further, because diet is the main source of fatty acid intake in humans, balancing protective and pro-inflammatory/cytotoxic fatty acid levels through dietary therapy may have beneficial effects, delaying T1D progression. Therefore, therapeutic interventions targeting fatty acid signaling hold potential as avenues to treat T1D.

Dietary Intake and Body Mass Index Influence the Risk of Islet Autoimmunity in Genetically At-Risk Children: A Mediation Analysis Using the TEDDY Cohort.

Background/Objective: Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods: Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results: We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. Conclusions: This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA.

HLA Genotype and Probiotics Modify the Association Between Timing of Solid Food Introduction and Islet Autoimmunity in the TEDDY Study.

OBJECTIVE: To study the interaction among HLA genotype, early probiotic exposure, and timing of complementary foods in relation to risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes. We used a Cox proportional hazards regression model adjusting for potential confounders to study early feeding and the risk of IA in a sample of 7,770 children. RESULTS: Any solid food introduced early (<6 months) was associated with increased risk of IA if the child had the HLA DR3/4 genotype and no probiotic exposure during the 1st year of life. Rice introduced at 4-5.9 months compared with later in the U.S. was associated with an increased risk of IA. CONCLUSIONS: Timing of solid food introduction, including rice, may be associated with IA in children with the HLA DR3/4 genotype not exposed to probiotics. The microbiome composition under these exposure combinations requires further study.

What is the role of puberty in the development of islet autoimmunity and progression to type 1 diabetes?

In many populations, the peak period of incidence of type 1 diabetes (T1D) has been observed to be around 10-14 years of age, coinciding with puberty, but direct evidence of the role of puberty in the development of T1D is limited. We therefore aimed to investigate whether puberty and the timing of its onset are associated with the development of islet autoimmunity (IA) and subsequent progression to T1D. A Finnish population-based cohort of children with HLA-DQB1-conferred susceptibility to T1D was followed from 7 years of age until 15 years of age or until a diagnosis of T1D (n = 6920). T1D-associated autoantibodies and growth were measured at 3- to 12-month intervals, and pubertal onset timing was assessed based on growth. The analyses used a three-state survival model. IA was defined as being either positive for islet cell antibodies plus at least one biochemical autoantibody (ICA + 1) or as being repeatedly positive for at least one biochemical autoantibody (BC1). Depending on the IA definition, either 303 (4.4%, ICA + 1) or 435 (6.3%, BC1) children tested positive for IA by the age of 7 years, and 211 (3.2%, ICA + 1)) or 198 (5.3%, BC1) developed IA during follow-up. A total of 172 (2.5%) individuals developed T1D during follow-up, of whom 169 were positive for IA prior to the clinical diagnosis. Puberty was associated with an increase in the risk of progression to T1D, but only from ICA + 1-defined IA (hazard ratio 1.57; 95% confidence interval 1.14, 2.16), and the timing of pubertal onset did not affect the association. No association between puberty and the risk of IA was detected. In conclusion, puberty may affect the risk of progression but is not a risk factor for IA.

Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study.

OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron. RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake. CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

Longitudinal consumption of fruits and vegetables and risk of asthma by 5 years of age.

BACKGROUND: Fruit and vegetable consumption has been linked to a decreased risk of asthma, but prospective evidence on longitudinal consumption in childhood is scarce. We aimed to investigate the association between fruit and vegetable consumption in childhood and the risk of asthma by the age of 5 years, and to explore the role of processing of fruits and vegetables in the Finnish Type 1 Diabetes Prediction and Prevention Allergy Study. METHODS: Child's food consumption was assessed by 3-day food records completed at the age of 3 and 6 months, and 1, 2, 3, 4, and 5 years, and asthma and allergies by a validated modified version of the ISAAC questionnaire at the age of 5 years. Consumption of processed and unprocessed fruits and vegetables was calculated. Joint models with a current value association structure for longitudinal and time-to-event data were used for statistical analyses. RESULTS: Of the 3053 children, 184 (6%) developed asthma by the age of 5 years. The risk of asthma was not associated with the consumption of all fruits and vegetables together (HR 1.00, 95%CI 0.99-1.01 per consumption of 1 g/MJ, adjusted for energy and other covariates), or with most subgroups. Weak inverse associations were seen between all leafy vegetables and asthma (HR = 0.87, 0.77-0.99), and unprocessed vegetables and nonatopic asthma (HR = 0.90, 95% CI 0.81-0.98). CONCLUSION: Total consumption of fruits and vegetables in childhood was not associated with the development of asthma by the age of 5 years. Weak inverse associations found for vegetables need to be confirmed or rejected in future studies.

Infant Feeding, Gut Permeability, and Gut Inflammation Markers.

OBJECTIVES: Increased gut permeability and gut inflammation have been linked to the development of type 1 diabetes. Little is known on whether and how intake of different foods is linked to these mechanisms in infancy. We investigated whether the amount of breast milk and intake of other foods are associated with gut inflammation marker concentrations and permeability. METHODS: Seventy-three infants were followed from birth to 12 months of age. Their diet was assessed with structured questionnaires and 3-day weighed food records at the age of 3, 6, 9, and 12 months. Gut permeability was assessed with the lactulose/mannitol test and fecal calprotectin and human ß-defensin-2 (HBD-2) concentrations were analyzed from stool samples at the age of 3, 6, 9, and 12 months. The associations between foods and gut inflammation marker concentrations and permeability were analyzed using generalized estimating equations. RESULTS: Gut permeability and gut inflammation marker concentrations decreased during the first year of life. Intake of hydrolyzed infant formula ( P = 0.003) and intake of fruits and juices ( P = 0.001) were associated with lower intestinal permeability. Intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and oats ( P = 0.003) were associated with lower concentrations of HBD-2. Higher intake of breast milk was associated with higher fecal calprotectin concentrations ( P < 0.001), while intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and potatoes ( P = 0.007) were associated with lower calprotectin concentrations. CONCLUSIONS: Higher intake of breast milk may contribute to higher calprotectin concentration, whereas several complementary foods may decrease gut permeability and concentrations of calprotectin and HBD-2 in infant gut.

Intake and sources of dietary fibre and dietary fibre fractions in Finnish children.

The current definition of dietary fibre was adopted by the Codex Alimentarius Commission in 2009, but implementation requires updating food composition databases with values based on appropriate analysis methods. Previous data on population intakes of dietary fibre fractions are sparse. We studied the intake and sources of total dietary fibre (TDF) and dietary fibre fractions insoluble dietary fibre (IDF), dietary fibre soluble in water but insoluble in 76 % aqueous ethanol (SDFP) and dietary fibre soluble in water and soluble in 76 % aqueous ethanol (SDFS) in Finnish children based on new CODEX-compliant values of the Finnish National Food Composition Database Fineli. Our sample included 5193 children at increased genetic risk of type 1 diabetes from the Type 1 Diabetes Prediction and Prevention birth cohort, born between 1996 and 2004. We assessed the intake and sources based on 3-day food records collected at the ages of 6 months, 1, 3 and 6 years. Both absolute and energy-adjusted intakes of TDF were associated with age, sex and breast-feeding status of the child. Children of older parents, parents with a higher level of education, non-smoking mothers and children with no older siblings had higher energy-adjusted TDF intake. IDF was the major dietary fibre fraction in non-breastfed children, followed by SDFP and SDFS. Cereal products, fruits and berries, potatoes and vegetables were major food sources of dietary fibre. Breast milk was a major source of dietary fibre in 6-month-olds due to its human milk oligosaccharide content and resulted in high SDFS intakes in breastfed children.

Impact of Cultivation and Origin on the Fruit Microbiome of Apples and Blueberries and Implications for the Exposome.

Vegetables and fruits are a crucial part of the planetary health diet, directly affecting human health and the gut microbiome. The objective of our study was to understand the variability of the fruit (apple and blueberry) microbiome in the frame of the exposome concept. The study covered two fruit-bearing woody species, apple and blueberry, two countries of origin (Austria and Finland), and two fruit production methods (naturally grown and horticultural). Microbial abundance, diversity, and community structures were significantly different for apples and blueberries and strongly influenced by the growing system (naturally grown or horticultural) and country of origin (Austria or Finland). Our results indicated that bacterial communities are more responsive towards these factors than fungal communities. We found that fruits grown in the wild and within home gardens generally carry a higher microbial diversity, while commercial horticulture homogenized the microbiome independent of the country of origin. This can be explained by horticultural management, including pesticide use and post-harvest treatments. Specific taxonomic indicators were identified for each group, i.e., for horticultural apples: Pseudomonas, Ralstonia, and Stenotrophomonas. Interestingly, Ralstonia was also found to be enriched in horticultural blueberries in comparison to such that were home and wildly grown. Our study showed that the origin of fruits can strongly influence the diversity and composition of their microbiome, which means that we are exposed to different microorganisms by eating fruits from different origins. Thus, the fruit microbiome needs to be considered an important but relatively unexplored external exposomic factor.

Dietary fatty acid intake in childhood and the risk of islet autoimmunity and type 1 diabetes: the DIPP birth cohort study.

PURPOSE: The aim was to study the associations between dietary intake of fatty acids in childhood and the risk of islet autoimmunity and type 1 diabetes (T1D). METHODS: The prospective Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study included children with genetic susceptibility to T1D born between 1996 and 2004. Participants were followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Dietary intake of several fatty acids at the age of 3 months to 6 years was assessed 1-8 times per participant with a 3-day food record. Joint models adjusted for energy intake, sex, HLA genotype and familial diabetes were used to investigate the associations of longitudinal intake of fatty acids and the development of islet autoimmunity and T1D. RESULTS: During the 6-year follow-up, 247 (4.4%) children of 5626 developed islet autoimmunity and 94 (1.7%) children of 5674 developed T1D. Higher intake of monounsaturated fatty acids (HR 0.63; 95% CI 0.47, 0.82), arachidonic acid (0.69; 0.50, 0.94), total n-3 fatty acids (0.64; 0.48, 0.84), and long-chain n-3 fatty acids (0.14; 0.04, 0.43), was associated with a decreased risk of islet autoimmunity with and without energy adjustment. Higher intake of total fat (0.73; 0.53, 0.98), and saturated fatty acids (0.55; 0.33, 0.90) was associated with a decreased risk of T1D only when energy adjusted. CONCLUSION: Intake of several fatty acids was associated with a decreased risk of islet autoimmunity or T1D among high-risk children. Our findings support the idea that dietary factors, including n-3 fatty acids, may play a role in the disease process of T1D.

Relationships of Local Food and Physical Activity Environments With Overweight in 5- to 17-Year-Old Malaysian Children.

Evidence on the associations between built environment and overweight in children outside developed countries is scarce. We examined associations between access to local food and physical activity environments and overweight in 5- to 17-year-old Malaysians in two states with differing overweight levels. Information on children was measured in the National Health and Morbidity Survey 2015 and combined with Geographic Information System-derived data on local food and physical activity environments. Access to the built environment was measured by presence and distance from child's residence. Complete data were available for 880 children. Access to local food outlets and parks was higher and associated with higher occurrence of overweight in children living in the state with higher overweight prevalence. When adjusted for sociodemographic factors, higher presence of and shorter distance to convenience stores and parks were associated with overweight. Both built environment and children's sociodemographic backgrounds should be considered when planning interventions to curb the overweight epidemic in Malaysia.

Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism.

The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative analysis expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.

Comprehensive self-tracking of blood glucose and lifestyle with a mobile application in the management of gestational diabetes: a study protocol for a randomised controlled trial (eMOM GDM study).

INTRODUCTION: Gestational diabetes (GDM) causes various adverse short-term and long-term consequences for the mother and child, and its incidence is increasing globally. So far, the most promising digital health interventions for GDM management have involved healthcare professionals to provide guidance and feedback. The principal aim of this study is to evaluate the effects of comprehensive and real-time self-tracking with eMOM GDM mobile application (app) on glucose levels in women with GDM, and more broadly, on different other maternal and neonatal outcomes. METHODS AND ANALYSIS: This randomised controlled trial is carried out in Helsinki metropolitan area. We randomise 200 pregnant women with GDM into the intervention and the control group at gestational week (GW) 24-28 (baseline, BL). The intervention group receives standard antenatal care and the eMOM GDM app, while the control group will receive only standard care. Participants in the intervention group use the eMOM GDM app with continuous glucose metre (CGM) and activity bracelet for 1 week every month until delivery and an electronic 3-day food record every month until delivery. The follow-up visit after intervention takes place 3 months post partum for both groups. Data are collected by laboratory blood tests, clinical measurements, capillary glucose measures, wearable sensors, air displacement plethysmography and digital questionnaires. The primary outcome is fasting plasma glucose change from BL to GW 35-37. Secondary outcomes include, for example, self-tracked capillary fasting and postprandial glucose measures, change in gestational weight gain, change in nutrition quality, change in physical activity, medication use due to GDM, birth weight and fat percentage of the child. ETHICS AND DISSEMINATION: The study has been approved by Ethics Committee of the Helsinki and Uusimaa Hospital District. The results will be presented in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: NCT04714762.

Serum 25-hydroxyvitamin D and fatty acids in relation to the risk of microbial infections in children: The TRIGR Divia study.

BACKGROUND & AIMS: Nutrient status may affect the risk of microbial infections and play a role in modulating the immune response against such infections. The aim of this study was to determine whether serum 25-hydroxyvitamin D [25(OH)D] and serum fatty acids in infancy are associated with microbial infections by the age of 18 months. METHODS: Altogether 576 newborn infants from Trial to Reduce IDDM in the Genetically at Risk (TRIGR) born between 2002 and 2007 were included. The concentration of 25(OH)D vitamin and proportions of 26 fatty acids (presented as % of total fatty acids) were analyzed in cord blood serum and in sera taken at 6, 12, and 18 months of age. The cord blood samples and mean of 6-18-month values were used as exposures. Infections were detected by screening IgG antibodies against 10 microbes using enzyme immunoassay and antibodies against 6 coxsackievirus B serotypes by plaque neutralization assay in serum samples taken at 18 months of age. RESULTS: A higher proportion of n-3 polyunsaturated fatty acids (PUFAs) and especially long-chain n-3 PUFAs at birth and at the age of 6-18 months was associated with decreased risk of coxsackievirus B2 infection unadjusted and adjusted for region, case-control status, and maternal type 1 diabetes. Higher proportion of docosapentaenoic acid (DPA, 22:5 n-3) at birth was associated with a decreased risk of respiratory syncytial virus infection. 25(OH)D vitamin concentration was not consistently associated with the risk of infections. When only infected children were included docosahexaenoic acid (DHA, 22:6 n-3) and arachidonic acid (20:4 n-6) proportions were positively associated with IgG antibody levels against influenza A virus. 25(OH)D vitamin concentration showed an inverse association with rotavirus IgG levels among children with rotavirus seropositivity. CONCLUSIONS: In young children with increased susceptibility to type 1 diabetes, long-chain n-3 PUFAs may influence the risk of viral infections and immune response against the infections. However, this association may depend on the type of virus suggesting virus-specific effects.

Modulation of the food microbiome by apple fruit processing.

During the early life, introduction to external exposures such as consumption of solid foods contribute to the development of the gut microbiota. Among solid foods, fruit and vegetables are normally consumed during early childhood making them key components of a healthy human diet. The role of the indigenous microbiota of fruits as a source for beneficial gut microbes, especially during food processing, is largely unknown. Therefore, we investigated the apple fruit microbiota before and after processing using functional assays, advanced microscopic as well as sequencing technologies. Apple fruits carried a high absolute bacterial abundance (1.8 × 105 16S rRNA copies per g of apple pulp) and diversity of bacteria (Shannon diversity index = 2.5). We found that heat and mechanical treatment substantially affected the fruit's microbiota following a declining gradient of absolute bacterial abundance and bacterial diversity from shredded > boiled > pureed > preserved > dried apples. Betaproteobacteriales and Enterobacteriales were the two dominant bacterial orders (51.3%, 20.4% of the total 16S rRNA sequence reads) in the unprocessed apple. Boiling and air drying reduced the microbial load, but an unexpected, substantial fraction of 1/3 of the microbiota survived. Boiling and air drying shifted the microbiota leading to a relative increase in low abundant taxa such as Pseudomonas and Ralstonia (>2 log2 fold change), while others such as Bacillus decreased. Bacillus spp., frequently found in raw fruits, were shown to have specific traits, i.e. antagonist activity against opportunistic pathogens, biosurfactant production, and bile salt resistance indicating a probiotic potential. Our findings provide novel insights into food microbial changes during processing and demonstrate that food microbiome studies need a combined methodological approach. Food inhabiting microbes, currently considered being a risk factor for food safety, are a potential resource for the infant gut microbiome.