A true rise in pediatric coeliac disease

Consider this something of a micro blog post as I offer up your scientific TV dinner today in the form of the paper by White and colleagues* (open-access) on the numbers game when it comes to coeliac disease (even celiac disease if you prefer) in children.

On the understanding that not everyone knows about the currently known hows and whys of coeliac disease (CD) - the premier autoimmune condition linked to the protein gluten - readers might want to check out my CD mega-post over on a sister blog (see here).

Self-promotion over and done with, the paper from White et al looking at the incidence (that's incidence not prevalence) of CD is an important one, because as the authors conclude: "The significant increase in classic cases is strongly suggestive of a true rise in CD incidence". In other words, it's not just about better case ascertainment, at least when it comes to CD in Scotland.

So to the next question: 'why the increase?' We've been given a few areas that might require some further investigation (see here and here and here) but I'm not going to make any sweeping generalisations at this time.

Gluten exclusion for cases of diarrhoea predominant IBS

If I had the intellect I would try and deliver this very concise entry in the form of a witty poem or ditty just to try and make things a little more entertaining for readers rather than enduring yet another dry excuse for not making a proper "chatty" post. Unfortunately, I am to poetry what chocolate is to teapot material, so won't even try.

Instead I offer a link to a potentially very, very interesting trial by Maria Vazquez–Roque and colleagues* (open-access) reporting physiological results based on the use of a gluten-free diet for cases of irritable bowel syndrome (IBS) diarrhoea predominant type. The accompanying editorial by Lowe and Moseley** does a great job of summing up what Vazquez-Roque et al found, so leaves me very little to add.

Basically, under randomised-controlled conditions, "Patients on the gluten-containing diet exhibited greater small intestinal permeability than those on the gluten-free diet. The study was able to measure significant changes that provided physiologic support for a gluten-free diet in patients with IBS-D without celiac disease".

Whilst small intestinal permeability - also known as gut hyperpermeability or leaky gut - is already discussed in coeliac disease (CD) circles, the added-value from this recent trial is the suggestion that the effect of gluten on permeability might extend slightly outside of just diagnosed CD. I'm not getting into the nitty-gritty of the MHC and those CD-related serotypes at this point even though they were important to the findings. Also too were some interesting results based on those tight junction proteins including 'General' zonulin.

I do wonder how far outside of CD and indeed IBS-D we might venture with these findings. Y'know that very interesting paper from Laura de Magistris and colleagues*** (discussed here) with autism in mind; bearing in mind of course the experimental differences between the studies and that autism is not IBS....

Maybe also at this point I'll also introduce the latest study by Jessica Biesiekierski and colleagues**** on non-coeliac gluten sensitivity (see here) in relation to FODMAPs and gluten as further fodder for consumption.

Now, 'the boy stood on the burning deck....' (scroll down the link to see the Spike Milligan parody).

---------

* Vazquez–Roque MI. et al. A Controlled Trial of Gluten-Free Diet in Patients With Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function. Gastroenterology. 2013; 144: 903-911.

** Lowe AW. & Moseley RH. Covering the Cover. Gastroenterology. 2013; 144: 859-862.

*** de Magistris L. et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010; 51: 418-424.

**** Biesiekierski JR. et al. No Effects of Gluten in Patients with Self-Reported Non-Celiac Gluten Sensitivity Following Dietary Reduction of Low-Fermentable, Poorly-Absorbed, Short-Chain Carbohydrates. Gastroenterology. May 2013.

----------

Gluten, guts and glory

Yep, I know. First post for several months - indeed first post for 2013 - and more apologies to readers about not keeping up with this blog. A short post on this occasion focused on an interesting opinion piece by Moises Velasquez-Manoff titled: Who has the guts for gluten?

I'll admit to being pretty entertained by the work of Velasquez-Manoff given his previous articles crossing over into topics like autism spectrum disorders (see here and also covered here). This latest piece is equally thought-provoking and alongside the opinions of people like Alessio Fasano, he of the [General] zonulin (see here), asks some potentially important questions about our relationship with gluten.

One quote in particular caught my attention from Dr Fasano: “Keep the lactobacilli high enough in the guts of these kids, and you prevent autoimmunity.” following some observations based on the onset of type 1 diabetes and coeliac (celiac) disease.

I'm intrigued and am waiting for that confirmatory peer-reviewed evidence.

Newsflash: defining gluten-related disorders

In the style of one Homer J Simpson... can't stop... must finish for the day.. new guidance of what constitutes a gluten-related disorder just published by Sapone and colleagues*.

If there is one document that you absolutely have to look at which summarises where we are in relation to gluten-related conditions, not just coeliac disease, this is it.

It's full-text, has a myriad of gluten research names included on it (including Alessio Fasano, Marios Hadjivassiliou and David Sanders), so enjoy.

* Sapone A. et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. February 2012.
DOI: 10.1186/1741-7015-10-13

Gluten, bacteria and mouthwash

Peptides. Those short-ish chains of amino acids, are interesting characters. Therapeutically, certain peptides have the propensity to do great things as exemplified by compounds such as the glucagon-like peptides and speculation on a therapeutic role in conditions like diabetes and intestinal disease.

In terms of 'disease' and ill-health, other peptides have a slightly less desirable side; something which I have been interested in for a few years speculatively in relation to conditions such as autism and schizophrenia. Peptides, such as those immunogenic epitopes derived from gluten, in relation to coeliac (celiac) disease (CD) also perhaps show a less speculative negative side in terms of effect.

What can be done about these immune-stimulating gluten peptides? Well, you could try and break them down via enzymes such as endopeptidases. There are also lots of products on the market which claim to do similar things (bearing in mind that I offer no endorsement). A recent paper by Zamakchari and colleagues* also offers another potential solution: certain enzymes produced by bacteria with the propensity to degrade gluten.

Before you go scouring the Internet for some commercial bacterial supplement, know that the authors suggested that we might already have such bacteria in our 'oral cavity' (mouth in plain speak); in our saliva and dental plaque.

The paper summary:

• Human dental plaque and saliva were collected from willing volunteers and the various oral micro-organisms cultured. Those bacteria with gliadin-degrading activity were identified by 16S rDNA analysis, a sort of molecular fingerprinting service.
• Various bacterial strains were added to synthetic immunogenic peptide sequences from gliadin and the subsequent effects separated and characterised by a combination of reversed-phase HPLC and mass spectrometric detection (MS/MS).
• The results: 27 aerobic and 30 anaerobic bacterial strains capable of metabolising gluten were found. All the final anaerobic strains cultured (n=10 fastest growing) were of the Bifidobacterium genus. The final aerobic strains (n=5 fastest growing) included bacteria of the Rothia genus.
• Several tri-peptide combinations appearing in the greatest frequency within the larger gluten peptides were broken down by individual bacterial strains. Rothia mucilaginosa and Rothia aeria seemed to come out top in terms of their hydrolysing abilities in terms of amounts and time taken. This effect was also noted when the larger immunogenic epitopes were exposed to the Rothia strains. 

There are a few important points to be taken from this research. First is the suggestion that digestion starts in the mouth and that all important motherly advice 'chew your food properly'. Masticating (or chewing to us mere mortals) is an important first step in presenting the food we eat to the rest of our hard-working gastrointestinal (GI) tract. Second is the suggestion that dental plaque (alongside saliva) might actually serve some purpose rather than just being something associated with poor oral hygiene and bad breath. I am not for one minute suggesting that we should all stop our regular tooth cleaning routine; but perhaps just step back and think about when you clean your teeth and what products you might use in your dental hygiene routine. Finally (finally!) I am already a big fan of the idea that our relationship with bacteria, some strains of bacteria, is an important one. A primary implication from this work is that 'addition' of bacteria to food or whilst eating certain foods (bearing in mind the effect of pH on these bacteria) might actually serve as another tool in the arsenal against conditions like coeliac disease, and even gluten sensitivity when it comes to degrading those very difficult gluten peptides. Please note that I am not recommending anything from this point given the slightly more negative press from these strains; just speculating.

* Zamakhchari M. et al. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS ONE. September 2011.

Psychiatric comorbidity and coeliac disease

A short post this one following the recent publication of a paper by Danielle Arigo and colleagues* on the psychiatric comorbidity potentially accompanying a diagnosis of coeliac (celiac) disease (CD) in women. There is nothing particularly earth-shattering about the fact that people with coeliac disease or gluten sensitivity might be at greater risk of other comorbidities, particularly those based outside of the gastrointestinal (GI) tract. If you don't believe me, check out the work of Drs Mario Hadjivassiliou and David Sanders for example and even the suggestion that parts of conditions such as autism and schizophrenia might manifest as a result of dietary gluten.

The Arigo study suggested that despite high compliance with a gluten-free diet, women diagnosed with coeliac disease (N=177) were still reporting symptoms for conditions like depression (37%) and 'disordered eating' (22%) (disordered eating I assume meaning a recognised eating disorder). Whilst the authors suggest that additional psychosocial care might be required for women with CD, I think that this study provides a small snapshot into a more a complex pattern of conditions which perhaps requires further exploration.

Depression for example has cropped up in other studies of CD. This paper suggested pretty much the same thing in gluten-free compliant children with CD and prominent 'internalising' symptoms particularly in females. So perhaps age is not the deciding factor here.

As for eating disorders and CD, you might expect that the adoption of a gluten-free diet might make a person more likely to concentrate on the food they eat, but would it necessarily promote an eating disorder? I find this a little hard to swallow but as yet can offer no other evidence-based explanation aside from the fact that this is again not the first time that an association has been made (see here). If I was to be ultra-speculative (careful!) I might go back to the autism connection, and the suggestion that there may be some overlap in the 'cognitive phenotype' between autism and eating disorders; could this possibly overlap with those 'best responder' cases to dietary intervention in autism spectrum conditions?

* Arigo D. et al. Psychiatric comorbidities in women with celiac disease. Chronic Illness. September 2011.