Publikationsdatum:
2009-10-30
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256734/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256734/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maslowski, Kendle M -- Vieira, Angelica T -- Ng, Aylwin -- Kranich, Jan -- Sierro, Frederic -- Yu, Di -- Schilter, Heidi C -- Rolph, Michael S -- Mackay, Fabienne -- Artis, David -- Xavier, Ramnik J -- Teixeira, Mauro M -- Mackay, Charles R -- P30 DK040561/DK/NIDDK NIH HHS/ -- P30 DK040561-14/DK/NIDDK NIH HHS/ -- R01 AI061570/AI/NIAID NIH HHS/ -- R01 AI061570-06/AI/NIAID NIH HHS/ -- R01 AI074878/AI/NIAID NIH HHS/ -- R01 AI074878-02/AI/NIAID NIH HHS/ -- R01 AI095466/AI/NIAID NIH HHS/ -- R01 HL088297/HL/NHLBI NIH HHS/ -- R01 HL088297-02/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Oct 29;461(7268):1282-6. doi: 10.1038/nature08530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865172" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Acetates/therapeutic use
;
Animals
;
Arthritis/metabolism
;
Cells, Cultured
;
Chemotactic Factors/*metabolism
;
Colitis/drug therapy/metabolism/microbiology
;
Fatty Acids, Volatile/metabolism
;
Germ-Free Life
;
Humans
;
Inflammation/drug therapy/*metabolism/*microbiology
;
Intestines/*microbiology
;
Metagenome
;
Mice
;
Mice, Inbred C57BL
;
Neutrophils/metabolism
;
Oligonucleotide Array Sequence Analysis
;
Protein Array Analysis
;
Receptors, G-Protein-Coupled/deficiency/*metabolism
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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