The unfolding of bacterial homeostasis in the gut continues apace and with each new stone uncovered there are interesting pathways that provide avenues for exploration and explanation in the management of inflammatory bowel diseases and functional disorders.
A paper out in Science[1] has identified that the protein β-catenin has an important role to play in inflammation control (β-catenin is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells) plays an important role in the management of mucosal tolerance.
β-catenin signalling promotes the induction of regulatory T (TReg) cells while suppressing T helper 1 (TH1) and TH17 cells in the gut by maintaining intestinal dendritic cells (DCs) in a tolerogenic state.
Intestinal DCs, constitutive β-catenin signalling (which was shown to be independent of commensal bacteria) is needed to maintain intestinal homeostasis and tolerance through the induction of anti-inflammatory factors and the suppression of pro-inflammatory cytokines by these cells. Therefore, β-catenin is a potential target for the treatment of inflammatory bowel disease. The DC’s which are professional information delivering cells which collect data from the intestinal lumen contents, bacteria and other microbes need Vitamin A to be able to promote Treg cells.
This study noted that in the mouse model induced with inflammation that retinoic acid – the converted part of vitamin A would induce tolerance suggesting a role for β-catenin and retinoic acid in the management of inflammation in the gut.
β-catenin in intestinal dendritic cells was required for the expression of anti-inflammatory mediators such as retinoic acid–metabolizing enzymes, interleukin-10, and transforming growth factor–β, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells.
Comment
What natural agents are agonists to B catenin – meaning that they bind to relevant receptors to increase the availability or production of β-catenin in the gut, only really applicable where there is no condition associated with its unwanted increase such as colorectal cancer.
In the case of unwanted β-catenin you may want to explore the use of green tea extract – tea polyphenol epigallocatechin-3-gallate (EGCG).[2]
As yet no natural agent has been explored to see if they have a promoting effect – but this will change soon as many scientists are looking for safe strategies t o resolve functional inflammation and loss of tolerance.
References
[1] Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez RM, Wang YC, Pulendran B. Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010 Aug 13;329(5993):849-53 View Abstract
[2] Dashwood WM, Carter O, Al-Fageeh M, Li Q, Dashwood RH. Lysosomal trafficking of beta-catenin induced by the tea polyphenol epigallocatechin-3-gallate. Mutat Res. 2005 Dec 11;591(1-2):161-72. Epub 2005 Jul 27 View Abstract
3 Comments. Leave new
This is interesting, to me in particular as a intestinally-compromised type. Is it worth giving green tea extract a try to reduce gut-based inflammation, and if so, by what mechanism does it work?
Hi Roger.
My post was a little unclear and so I have updated the last section. Natural agonists or promoters of B-Catenin surely exist, but there are no published studies on what may be used unlike those that may inhibit B-Catenin in the case of overexpression and the resulting alteration in inflammatory balance. Here green tea has been shown to have an effect. So how do we determine if you have an over or under expression – well unless you are willingto be sacrificed and opened up and your inner epithelial tissues analysed we are currently in the realms of future therapies rather than current options.
It is possible that Tumeric will be found to have a modulating effect of B-Catenin as there are anumber of related studies on scondary immune related molecules, so this may be an option a bit later
Mike
Thanks Mike. Sacrifice sounds like an interesting treatment option, I’ll discuss it with the wife – I’m sure she’ll be positive.