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Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to
Heli Siljander1, Eeva Jason2, Terhi Ruohtula3
1Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Insights
Weaning infants at high risk for type 1 diabetes to extensively hydrolyzed formula (EHF) significantly reduced gut permeability. This dietary intervention may lower early exposure to dietary antigens in susceptible infants.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Nutrition Science
Background:
- Infants with HLA-conferred susceptibility for type 1 diabetes are at increased risk.
- Early life nutrition plays a critical role in immune development and gut health.
- Understanding the impact of formula type on gut barrier function is crucial for at-risk infants.
Purpose of the Study:
- To evaluate if extensively hydrolyzed formula (EHF) reduces gut permeability and intestinal inflammation markers in infants with type 1 diabetes susceptibility.
- To compare EHF with conventional formula in this high-risk infant population.
Main Methods:
- Randomized controlled trial involving 73 infants with HLA-conferred type 1 diabetes susceptibility.
- Infants received either EHF or conventional formula from 3 to 9 months of age if not breastfed.
- Gut permeability assessed by lactulose to mannitol ratio (L/M ratio) at 9 months; secondary outcomes included L/M ratio at other time points and fecal markers.
Main Results:
- The EHF group showed a significantly lower median L/M ratio at 9 months compared to the control group (0.006 vs. 0.028, P=0.005).
- No significant differences were observed in other intestinal permeability markers, fecal calprotectin, or human beta-defensin 2 (HBD-2) levels between groups.
- Some age-related dynamic differences in markers were noted.
Conclusions:
- Weaning to an extensively hydrolyzed formula can decrease intestinal permeability in infants.
- This dietary approach may mitigate early exposure to dietary antigens in susceptible infants.
- Further research is warranted to explore long-term implications.
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.
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