Sodium butyrate converts Caco-2 monolayers into a leaky but healthy intestinal barrier resembling that of a newborn infant

A simple and reliable in vitro model of the infant intestinal barrier is needed to study nutrient absorption and drug permeability specifically for this life stage. This study investigated the treatment of 20 day old differentiated Caco-2 monolayers with sodium butyrate at various concentrations (0-...

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Bibliographic Details
Published in:Food & function 2021-06, Vol.12 (11), p.566-576
Main Authors: Kondrashina, Alina, Brodkorb, Andre, Giblin, Linda
Format: Article
Language:English
Subjects:
Cytokines
Cytotoxicity
Electrical resistivity
Immunofluorescence
Infants
Inflammation
Inflammatory response
Interleukin 6
Intestine
Lactulose
Mannitol
Membrane permeability
Monolayers
Permeability
Protein transport
Proteins
Sodium
Sodium butyrate
Toxicity
Tumor necrosis factor-α
Zonula occludens-1 protein
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Summary:A simple and reliable in vitro model of the infant intestinal barrier is needed to study nutrient absorption and drug permeability specifically for this life stage. This study investigated the treatment of 20 day old differentiated Caco-2 monolayers with sodium butyrate at various concentrations (0-250 mM). Monolayer integrity, cytotoxicity, permeability and inflammatory response were tracked. An intestinal barrier model, with infant gut characteristics, was developed based on the treatment of mature monolayers with 125 mM sodium butyrate for 24 h. Such treatment was not cytotoxic but caused a stable transepithelial electrical resistance value of 408 ± 52 Ω cm 2 . The ratio of lactulose to mannitol transport across the intestinal barrier increased 1.79-fold. Redistribution of the tight junction proteins, occludin and ZO-1, in response to sodium butyrate treatment was visualized with immunofluorescence. Levels of the cytokines, TNF-α and IL-6, although modestly increased did not indicate an inflammatory response by Caco-2 to sodium butyrate. This intestinal barrier demonstrated physiologically relevant transport rates for dairy protein of 0.01-0.06%, suggesting it may be used to track permeability of proteins in infant nutritional products. Treating Caco2 monolayers with sodium butyrate will create, in vitro , a leaky but healthy gut barrier that closely resembles that of a newborn baby.
ISSN:2042-6496
2042-650X
DOI:10.1039/d1fo00519g