Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study

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).

The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

“…The present observational prospective cohort study continues research efforts in the context of intestinal barrier function in a cohort of Polish newborns, described in detail in previous publications [28,29]. Twenty four healthy full-term newborns at the Department of Obstetrics, Gynecology and Neonatology, the Pomeranian Medical University/Independent Public Clinical Hospital No.…”

“…Of note, the microbial changes in the rst two years of life are very dynamic and depend on the mode of delivery, feeding, antibiotic treatment, and other environmental factors. [28,29] However, a comprehensive analysis of all factors in uencing the gut microbiota is beyond the scope of this study, which is focused on the relationship between the microbiota and the fecal zonulin and calprotectin content. This said the compositional and functional comparison of the PMU and HMS cohorts' microbiota would be very interesting.…”

“…Additionally, we found that after birth, zonulin levels increased up until 12 months of age, remaining high thereafter, while calprotectin levels decreased until six months of age, stabilizing thereafter. [29] Of note, in this previous study, we did not assess the fecal microbiota, which was a signi cant limitation; we were not able to trace the relationships between the fecal microbiome and the concentrations of the abovementioned stool markers. Therefore, in this study, we decided to analyze the microbiota in faecal samples collected longitudinally over 24 months from 21 subjects to test the hypothesis that small intestinal barrier permeability is linked to the gut microbiota.…”

“…The concentrations of zonulin and calprotectin in the fecal samples were measured as previously described. [28,29].…”

Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy: Does It Matter in Clinical Practice? A Retrospective Observational Study

“…Elevated FC levels have also been associated with the use of nonsteroid anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), and proton-pump inhibitors (PPIs) [17][18][19]. Furthermore, FC levels are affected by age, that is, elevated levels are seen in the elderly as well as in neonates [19,20].…”