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.

Consumption of differently processed milk products and the risk of asthma in children.

BACKGROUND: Consumption of unprocessed cow's milk has been associated with a lower risk of childhood asthma and/or atopy. Not much is known about differently processed milk products. We aimed to study the association between the consumption of differently processed milk products and asthma risk in a Finnish birth cohort. METHODS: We included 3053 children from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Asthma and its subtypes were assessed at the age of 5 years, and food consumption by food records, at the age of 3 and 6 months and 1, 2, 3, 4, and 5 years. We used conventional and processing (heat treatment and homogenization)-based classifications for milk products. The data were analyzed using a joint model for longitudinal and time-to-event data. RESULTS: At the age of 5 years, 184 (6.0%) children had asthma, of whom 101 (54.9%) were atopic, 75 (40.8%) were nonatopic, and eight (4.3%) could not be categorized. Consumption of infant formulas [adjusted hazard ratio (95% confidence intervals) 1.15 (1.07, 1.23), p < .001] and strongly heat-treated milk products [1.06 (1.01, 1.10), p = .01] was associated with the risk of all asthma. Consumption of all cow's milk products [1.09 (1.03, 1.15), p = .003], nonfermented milk products [1.08 (1.02, 1.14), p = .008], infant formulas [1.23 (1.13, 1.34), p < .001], and strongly heat-treated milk products [1.08 (1.02, 1.15), p = .006] was associated with nonatopic asthma risk. All these associations remained statistically significant after multiple testing correction. CONCLUSIONS: High consumption of infant formula and other strongly heat-treated milk products may be associated with the development of asthma.

Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial.

OBJECTIVES: To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. STUDY DESIGN: By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9 months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. RESULTS: Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs .028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. CONCLUSIONS: It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01735123.

Consumption of differently processed milk products in infancy and early childhood and the risk of islet autoimmunity.

Several prospective studies have shown an association between cows' milk consumption and the risk of islet autoimmunity and/or type 1 diabetes. We wanted to study whether processing of milk plays a role. A population-based birth cohort of 6081 children with HLA-DQB1-conferred risk to type 1 diabetes was followed until the age of 15 years. We included 5545 children in the analyses. Food records were completed at the ages of 3 and 6 months and 1, 2, 3, 4 and 6 years, and diabetes-associated autoantibodies were measured at 3-12-month intervals. For milk products in the food composition database, we used conventional and processing-based classifications. We analysed the data using a joint model for longitudinal and time-to-event data. By the age of 6 years, islet autoimmunity developed in 246 children. Consumption of all cows' milk products together (energy-adjusted hazard ratio 1·06; 95 % CI 1·02, 1·11; P = 0·003), non-fermented milk products (1·06; 95 % CI 1·01, 1·10; P = 0·011) and fermented milk products (1·35; 95 % CI 1·10, 1·67; P = 0·005) was associated with an increased risk of islet autoimmunity. The early milk consumption was not associated with the risk beyond 6 years. We observed no clear differences based on milk homogenisation and heat treatment. Our results are consistent with the previous studies, which indicate that high milk consumption may cause islet autoimmunity in children at increased genetic risk. The study did not identify any specific type of milk processing that would clearly stand out as a sole risk factor apart from other milk products.