Chance discovery links inflammatory bowel disease with common bacterial gut toxin

[Indigophoton]

Another nail in the coffin of MUS-type designations...

New research has uncovered a surprise link between a common bacterial toxin found in the gut and inflammatory bowel disease (IBD).


The researchers at the John Innes Centre, Norwich, UK, working alongside a team of scientists from Brigham and Women's Hospital (Boston, USA), have helped establish a connection between microcin B17, a well-known toxin produced by E. coli bacteria, and IBD.

IBD includes long-term conditions such Crohn's disease and ulcerative colitis which together affect more than 300,000 people in the UK.

The research, published today in the peer-reviewed journal Cell, raises prospects of future therapy for IBD sufferers.

The article,https://medicalxpress.com/news/2018-05-chance-discovery-links-inflammatory-bowel.amp

Highlights

• •Oxazoles derived from diet, industrial sources, and microbes activate IDO1
• •Environmental oxazoles induce tryptophan-derived metabolites to activate AhR in IECs
• •AhR activation in IECs limits CD1d-restricted production of IL-10
• •Oxazole activation of AhR in IECs results in iNKT-mediated intestinal inflammation

Summary
Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs). CD1d-restricted production of interleukin 10 by IECs is limited through activity of the aryl hydrocarbon receptor (AhR) pathway in response to oxazole induction of tryptophan metabolites. As such, the depletion of the AhR in the intestinal epithelium abrogates oxazole-induced inflammation. In summary, we identify environmentally derived oxazoles as triggers of CD1d-dependent intestinal inflammatory responses that occur via activation of the AhR in the intestinal epithelium.

https://www.cell.com/cell/fulltext/S0092-8674(18)30568-3

Full paper here, http://sci-hub.tw/10.1016/j.cell.2018.04.037

 

[hixxy]

Another nail in the coffin of MUS-type designations...

I've never heard IBD (not IBS) linked to MUS?

 

[Arnie Pye]

I've never heard IBD (not IBS) linked to MUS?

I wonder how many people with IBD are fobbed off with a diagnosis of IBS for years. I suspect a fairly large proportion of the people frequenting this forum have been diagnosed with IBS at one time or another, particularly if they are female with gynaecological problems. It's a diagnosis that doctors appear to love because it allows them to do absolutely nothing, and feel virtuous about it.

 

[Forbin]

This is probably a very big deal if it's been published in "Cell," one of top-ranked peer reviewed scientific journals.

"They produce these toxins to kill their neighbours in their fight for ecological niches but it appears that the breakdown products of the toxin can initiate gut inflammation."

Makes me wonder what else bacterial toxins and their breakdown products are doing that we don't know about.