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| Kofi... |
 Posted: Fri Oct 30, 2009 3:31 am |
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Nature. 2009 Oct 29;461(7268):1282-6.
Regulation of inflammatory responses by gut microbiota and
chemoattractant receptor GPR43.
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC,
Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR.
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst,
New South Wales 2010, Australia.
The immune system responds to pathogens by a variety of pattern
recognition molecules such as the Toll-like receptors (TLRs), which
promote recognition of dangerous foreign pathogens. However, recent
evidence indicates that normal intestinal microbiota might also
positively influence immune responses, and protect against the
development of inflammatory diseases. One of these elements may be
short-chain fatty acids (SCFAs), which are produced by fermentation of
dietary fibre by intestinal microbiota. A feature of human ulcerative
colitis and other colitic diseases is a change in 'healthy' microbiota
such as Bifidobacterium and Bacteriodes, and a concurrent reduction in
SCFAs. Moreover, increased intake of fermentable dietary fibre, or
SCFAs, seems to be clinically beneficial in the treatment of colitis.
SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as
FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect
inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for
the normal resolution of certain inflammatory responses, because
GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving
inflammation in models of colitis, arthritis and asthma. This seemed to
relate to increased production of inflammatory mediators by Gpr43(-/-)
immune cells, and increased immune cell recruitment. Germ-free mice,
which are devoid of bacteria and express little or no SCFAs, showed a
similar dysregulation of certain inflammatory responses. GPR43 binding
of SCFAs potentially provides a molecular link between diet,
gastrointestinal bacterial metabolism, and immune and inflammatory
responses.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19865172 |
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