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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

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Title: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
Creators Name:Kaczmarczyk, M. and Löber, U. and Adamek, K. and Węgrzyn, D. and Skonieczna-Żydecka, K. and Malinowski, D. and Łoniewski, I. and Markó, L. and Ulas, T. and Forslund, S.K. and Łoniewska, B.
Abstract:BACKGROUND: The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scare. METHODS: We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. RESULTS: Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after chilbirth and begun to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first two years of life and were correlated with zonulin and calprotectin levels. Feacal calprotectin correlated inversely with alpha diversity (Shannon index, r =-0.30, FDR P (Q)=0.039). It also correlated with seven taxa; i.a. negatively with Ruminococccaceae (r=-0.34, Q=0.046), and Clostridiales (r=-0.34, Q=0.048) and positively with Stapylococcus (r=0.38, Q=0.023) and Staphylococcaceae (r=0.35, Q=0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r=-0.52, Q=0.0004), Clostridiales (r=0.48, Q=0.001) and the Ruminococcus (torques group) (r=0.40, Q=0.026). When time intevals were considered only changes in abundance of the Ruminococcus (torques group) were associcated with changes in calprotectin (β=2.94, SE=0.8, Q=0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β=-4.54, SE=1.08, Q=0.028) and Clostridium acetobutylicum fermentation (β=-4.48, SE=1.16, Q=0.026). CONCLUSIONS: The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first two years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.
Keywords:Zonulin, Calprotectin, Gut Microbiota, Gut Permeability, Newborn
Source:Research Square
Publisher:Research Square
Article Number:rs.3.rs-154335/v1
Date:29 January 2021
Official Publication:https://doi.org/10.21203/rs.3.rs-154335/v1
Related to:
https://edoc.mdc-berlin.de/20230/Final version

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