Implications of Indirect Biomarkers of Intestinal Permeability in the Stools of Newborns and Infants with Perinatal Risk Factors for Intestinal Colonization Disorders and Infant Feeding Patterns

Abstract

Background: The intestinal microbiota of pregnant women and factors disturbing the microbial balance of their gastrointestinal tract during the perinatal period may be the cause of dysbiosis and thus intestinal permeability syndrome in their children. The purpose of this study was to analyze the implications of intestinal permeability parameters in the stools of newborns and infants with perinatal risk factors for intestinal colonization disorders (the route of delivery, antibiotic therapy in the neonatal period and the abandonment of breastfeeding). Methods: The study included 100 mother–child pairs. All children were born from uncomplicated and term pregnancies (between 37 and 42 weeks of gestation). In order to determine the parameters of dysbiosis and intestinal permeability, we determined the concentrations of zonulin and occludin in stool samples taken from all children at 0 (i.e., at birth), 3, 6 and 12 months of age. Elevated levels of lipopolysaccharide (LPS) are associated with metabolic diseases and its presence may be indicative of TJ injury and the onset of leaky gut syndrome. To indirectly determine the presence of endotoxemia, the concentrations of lipopolysaccharide were also measured in stool samples taken from all children at 0, 3, 6 and 12 months of age. We analyzed the relationship between the markers studied and perinatal risk factors for impaired intestinal colonization, including the mode of delivery, the method of feeding, and a family history of allergy. Results: During the first 3 months of infant life, higher concentrations of fecal occludin and zonulin were most often accompanied by higher values of fecal LPS. Similarly, higher concentrations of zonulin were accompanied by higher values of occludin. There were no significant differences in the stool concentrations of the studied markers during the first year of life between children born by caesarean section and those born naturally. In addition, the method of feeding had no significant effect on the changes in the concentrations of the determined fractions. Antibiotic therapy was associated only with an increase in the fecal occludin concentration after birth, without any effect on zonulin, occludin or LPS levels. The use of probiotic therapy in infants resulted in a decrease in only LPS concentrations at 3 months of age, with no effect on zonulin or occludin concentrations at 0, 6 and 12 months. Conclusions: Perinatal factors related to intestinal permeability are important during the first 3 months of infant life. However, we found that the mode of delivery had no influence on the parameters of infant intestinal leakage during the first year of life. In addition, the mode of infant feeding—breast or exclusively formula—did not significantly affect the changes in the concentrations of LPS, zonulin or occludin in the stools of children. A short-term increase in occludin concentrations after delivery in the stools of children from mothers undergoing antibiotic therapy indicates a negative but reversible influence of intrapartum antibiotics on the intestinal integrity of children in the perinatal period. Probiotic therapy seems to have a positive effect on reducing endotoxemia in children during the first 3 months of life. The presence of LPS at 3 months did not affect intestinal tightness at any of the later measured periods of the infants’ lives.

Midgut Volvulus Adds a Murine, Neutrophil-Driven Model of Septic Condition to the Experimental Toolbox

“…Moreover, we also observed a pertinent number of CFU in liver, spleen and the lung of mice subject to LPS injection. As described previously by others, this finding is most likely to be explained by bacteremia resulting from an increased intestinal barrier permeability and bacterial translocation, which can be found in various systemic and inflammatory diseases and play an important role in the pathogenesis of sepsis induced organ failure [28,29].…”

Endotoxin Content in Neonatal Formulas, Fortification, and Lactoferrin Products: Effect on outcomes and need for measurement in enteral products and guidance on acceptable limits.

“…Some important neonatal factors include gut microbiome diversity, endothelial tight junction health, and the presence of other molecules, such as lactoferrin, which binds endotoxin. (Sochaczewska et al, 2022;Van Saene et al, 1992) Future studies should examine exotoxin stool levels with gut function and diseases as well as neonatal infectious related outcomes in preterm infants.…”

Programming Factors of Neonatal Intestinal Dysbiosis as a Cause of Disease

“…The limitation of zonulin as a parameter of intestinal inflammation is the small number of studies examining the neonatological population. In the study by Sochaczewska D et al [ 70 ], the concentration of zonulin, occludin, and lipopolysaccharide in the stool of newborns was determined as the parameter of dysbiosis and intestinal permeability. The limitations of the study are that the results depend on the method of delivery, the intake of probiotics, or the diet of the mother, so this marker cannot currently be used in the diagnostics of inflammatory bowel diseases [ 71 ].…”