@article{MAKHILLJAVA20181734558,
    title = {Natural Betaine Maintains Intestinal Epithelial Cell Integrity and
Energy Levels and Does Not Induce Immune Reactions in an <i>in vitro</i>
Caco-2 Model Compared with Synthetic Betaine-HCL},
    journal = {Journal of Animal and Veterinary Advances},
    volume = {17},
    number = {3},
    pages = {74-81},
    year = {2018},
    issn = {1680-5593},
    doi = {javaa.2018.74.81},
    url = {https://makhillpublications.co/view-article.php?issn=1680-5593&doi=javaa.2018.74.81},
    author = {H.,P.,K. and},
    keywords = {IL-8,transepithelial electrical resistance,ATP,in vitro digestion,Caco-2,influence animal},
    abstract = {Betaine is commonly used in feed, improving feed conversion ratios and performance in animals.
Betaine can be supplemented as natural betaine, isolated from natural sources; synthetic anhydrous betaine
or synthetic betaine-HCl. Scientific data on the comparison between synthetic betaine-HCl and natural betaine
are limited, prompting us to examine whether the 2 forms of betaine have disparate cellular effects. Natural
betaine or betaine-HCl was mixed with feed in equimolar amounts and subjected to <i>in vitro</i>
 digestion, mimicking
the conditions in the upper gastrointestinal tract of poultry. After digestion, the soluble component was
separated and Caco-2 intestinal epithelial cells were used to examine how soluble factors affect inflammatory
markers, ATP and tight junction integrity at 1, 6 and 24 h after treatment. Soluble factors from in vitro-digested
feed that was supplemented with betaine-HCl changed significantly compared with those from control feed or
feed to which natural betaine was added. Tight junction integrity at 1 and 6 h decreased, recovering to basal
levels at 24 h. ATP levels declined after 1 h and were restored to baseline values after 6 and 24 h. IL-8 rose after
6 and 24 h as did IL-6 after 24 h, indicating that betaine-HCl induces inflammatory responses in Caco-2 cells
compared with natural betaine and the control. Our results show that despite possessing the same core betaine
molecule, synthetic betaine-HCl induced cellular changes that were indicative of transient damage in cells.
Thus, the supplementation of feed with various sources of betaine is not equal at the cellular level which can
influence animal performance and welfare, especially during stress.}
    }