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I wanted to collect some of the info on NCGI in one place so that visitors who test negative but may still have an issue with gluten can be directed there. I'll add to this post as I find new links, but feel free to add or contribute anything you think may be of use! :)

Matt

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Useful links:

An overview from Alessio Fasano, one of the world's leading researchers on celiac and gluten sensitivity: https://www.youtube.com/watch?v=VvfTV57iPUY

Umberto Volta, another leading researcher in the field gives some of the latest findings about NCGI: 

Presentation slides from Dr Volta's visit to Coeliac UK  - NCGS about halfway through

A scholarly overview from celiac disease magazine: https://www.researchgate.net/profile/Knut_Lundin/publication/232528784_Non-celiac_Gluten_Sensitivity/links/09e415098bbe37c05b000000.pdf

A good overview from a sceptical but fair perspective: https://sciencebasedmedicine.org/a-balanced-look-at-gluten-sensitivity/

Another overview: https://celiac.org/celiac-disease/understanding-celiac-disease-2/non-celiac-gluten-sensitivity-2/

University of Chicago's excellent celiac site's take: http://www.cureceliacdisease.org/category/faq-non-celiac-gluten-sensitivity/

A compelling account in the British Medical Journal from an NCGI patient: http://www.bmj.com/content/345/bmj.e7982

Here's some positive news about a potential new test: http://www.medicaldaily.com/non-celiac-gluten-insensitivity-blood-test-392850

NCGI in children: 

 

NCGI and auto immune study: https://www.ncbi.nlm.nih.gov/pubmed/26026392

Also consider:

Fodmaps: http://www.kcl.ac.uk/lsm/research/divisions/dns/projects/fodmaps/faq.aspx This Monash study: http://fodmapmonash.blogspot.co.uk/2015/03/the-truth-behind-non-celiac-gluten.html suggested some who think they're reacting to gluten should actually be reducing fodmaps

Sibo: http://www.webmd.boots.com/digestive-disorders/small-intestinal-bacteria-sibo

 

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I used to work as a lab assistant in a parasitology lab.  Once a week at lab meetings, someone would pick a paper, present it, and then we would analyze it and pick it apart.  It was then that I realized that much research has holes, there are always more questions, and nothing is ever "proven" in science...unless you are Newton and discovering basic Laws of nature.  What you do have are experiments that demonstrate (hopefully) the question you are exploring, which then generate more questions.  I learned that there were many ways to look at the data.

 

So, with this in mind, I have been reading and rereading the paper "Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease."  I stay away from poular summaries of research papers because they almost always overreach their conclusions.  Here is the actual paper:

 

http://gut.bmj.com/content/early/2016/07/21/gutjnl-2016-311964

 

I'd like to discuss it with those who are interested. Because I think there are some really interesting things to notice.

 

First, please see this terrific, highly technical video about what happens with celiac disease.  I like it because it is technical.  Oversimplification doesn't help when you are trying to make sense of a complex process. 

 

https://www.youtube.com/watch?v=nXzBApAx5lY&app=desktop

 

Everyone keeps pointing to this paper as a potential screening test for NCGS. The paper does show that those with NCGS do have increased intestinal permeability as well as innate immune system response.  This is key.  NCGS is not in your head! And the paper probably does set the stage for establishing markers for NCGS.  However, look at the data points.  This is really important:

 

-  BOTH the celiac and NCGS cohorts showed increased intestinal permeability over healthy controls.  In some cases equally.  

 

-  BOTH celiac and NCGS cohorts showed significant response to native gliadin peptide over healthy controls (this is looking for IgG and IgA response to gliadin that is NOT deamidated.  It is the old anti gliadin antibody test that was thrown out in the US when DGP was discovered.  DGP is closely correlated to intestinal damage found in celiac disease.  In Europe, some labs are still running native anti gliadin antibody test because it appears to correlate with those who are HLA DQ2/8 positive, have no GI symptoms but neurological symptoms that resolve with a gluten free diet - namely gluten ataxia.).  

 

-  BOTH celiac and NCGS cohorts showed DGP IgG and IgA response over heathly controls.  Yes, the celiac response was higher than the NCGS response.  But the point is that the NCGS folks DO have tTG enzymes deamidating the gluten peptide.  Which means that the process described in the celiac video I posted above (secretory IgA binds to gliadin, which binds to a transferrin receptor, which moves the gliadin through the cell into the lamina propria, where tTG deamidates it creating DGP...) THIS is happening in some of the NCGS cohort.

 

-  HLA status is reported in a chart at the beginning of the paper.  I want to know if the positive DGP correlates to the HLA status.  Or what does it correlate to?

 

-  The only places where the NCGS cohort is remarkably higher than the celiac cohort is the IgM response to gliadin and the response to bacterial invasion through the compromised GI epithelial cells.  It is speculated that the immune system response in the gut due to celiac disease may keep these potential bacterial invaders at bay for the celiac cohort.  The fact that the bacteria in the gut make it into the blood stream of the NCGS as well as the IgM response (the first response of bacterial invasions) makes sense.  The overactive immune response of celiac disease helps keep the innate immune system response seen in NCGS at bay in the celiac cohort.  BUT the innate immune system response is STILL seen in the celiac cohort, at a lower lever than NCGS, but still higher than the healthy cohort.

 

So seriously, to me, as I look at this, I don't see a test for NCGS.  I see a demonstration of how similar NCGS is to celiac disease.  I see elevated DGP, elevated native AGA, I DON'T see elevated tTG, BUT, if there is DGP in the NCGS cohort, there must be tTG but it's not measurable. Why? I see intestinal permeability and adaptive immune system response (per the elevated native AGA).  The authors mention toll like receptors release pro-inflammatory cytokines in NCGS which leads to deleterious systemic effects...BUT that is also one of the steps in the celiac process (per the attached video) when the deamidated gliadin peptide binds to the HLA DQ2/8 antigen presenting cells.  That process produces cytokines that damage the epithelial cells.  Since some of the NCGS cohort are HLA DQ2/8 positive, it is possible that there is also that inflammatory response in the NCGS cohort but the damage is not detectable.

 

As much as everyone is talking about a test for NCGS, I see the demonstration of a pathway towards the development of celiac disease. 

 

Lots here.  Anyone with comments?  

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On 6/20/2017 at 8:01 PM, Feeneyja said:

Anyone with comments?  

What a great post! I will reply, I'm very interested in this topic too, but I'll do it when I have enough time to do your questions justice. :)

 

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