Abstract
Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: “Closure of the intestines” is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).
Highlights
The developing gastrointestinal system has important roles in the creation of a barrier to infectious materials as well as having a nutritional role [1]
Macromolecule intestinal permeability can be assessed by non-invasive methods and recently stool zonulin and calprotectin have been identified as markers of intestinal barrier development in healthy newborns
Children of mothers who had an increase in body mass index (BMI) > 5.7 during pregnancy showed a 73.7% increase in zonulin concentrations at 12 months of age (p = 0.049, r = 0.25)
Summary
The developing gastrointestinal system has important roles in the creation of a barrier to infectious materials as well as having a nutritional role [1]. Intestinal permeability is high and drops sharply after delivery, which leads to a process known as “gut closure” [2], a phenomenon which is poorly understood. Growth factors, hormones, breast milk and changes in the thickness and viscosity of the mucus gel layer play a role in this process [2,6,7]. “Gut closure” is associated with two physiological mechanisms [8]: (1) the movement of macromolecules from the lumen through paracellular spaces into the blood stream, and (2) the active transport of Immunoglobulin G (IgG) and immune complexes (ICs) from breast milk to the submucosa. Macromolecule intestinal permeability can be assessed by non-invasive methods (e.g., lactulose/mannitol test) and recently stool zonulin and calprotectin have been identified as markers of intestinal barrier development (with different kinetics concerning intestinal permeability) in healthy newborns
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