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.

Gut bacteria - obesity and coeliac disease - stem cells

Another very quick post to bring to your attention two very interesting papers which caught my attention recently.

The first is by Ciccocioppo and colleagues* and how, quote: "allogeneic HSCT may lead to induction of gluten tolerance in patients with CD [coeliac disease]." HSCT = hematopoietic stem cell transplantation, which is indeed as controversial as it sounds. Two patients, both with CD and β-thalassemia major who at 5 year follow-up after HSCT did not appear to show a reappearance of the some of the serological and histological markers of CD following gluten consumption. I'm not making any recommendations from this (or anything else) aside from stressing the need for quite a bit more research in this area.

The second paper by Liou and colleagues** suggested that based on a mouse model, changes to the gastrointestinal (GI) bacterial population following a gastric bypass might play some role in the weight loss above and beyond the surgery itself. This paper has received gallons of media coverage from places such as the BBC (see here) to Scientific American (see here) to Nature (see here). It's an interesting idea, that our gut bacteria might actually influence our body shape and particularly pertinent to our modern day obsession with weight and its health implications. That's not to say that this is the first time such a suggestion has been made (see this and this post from a sister blog) but at least now it is in the public consciousness and potentially opens the door to lots of possibilities not least the dreaded fecal bacterial transplant...

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* Ciccocioppo R. et al. Allogeneic Hematopoietic Stem Cell Transplantation May Restore Gluten Tolerance in Patients With Celiac Disease. J Pediatr Gastroenterol Nutr. 2013; 56: 422-427.

** Liou AP. et al. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Sci Transl Med 2013; 5: 178ra41.

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.

General Zod? No, General Zonulin

I hold my hands up and admit that gut hyperpermeability - leaky gut - is a bit of an obsession of mine. I know to some the mere mention of leaky gut conjures up images of 'alternative medicine' and all things tree-hugging. Just for the record I've never knowingly hugged any tree and am a meat eating, petrol car driving, house dwelling regular guy who has yet to dabble in anything 'alternative' assuming that the odd vitamin D tablet and probiotic counts as regular. Still I remain very interested in how abnormal gastrointestinal (GI) permeability might be tied into quite a few conditions.

One aspect of GI permeability in particular has surfaced quite recently on my research radar, an interesting compound called zonulin.

A description first. Zonulin enjoys quite a special place in the science of the tight junctions. Tight junctions (TJs) among other roles, serve quite an important barrier function in lots of parts of the body; so making sure that things stay in and other things stay out. Zonulin seems to be part and parcel of the chemistry of tight junctions and in particular sharing quite an important relationship with the enhanced permeability of TJs.

With the gut in mind, zonulin has found quite a bit of interest. A familiar name to this blog, Dr Alessio Fasano, seems to have been present right at the beginning of interest in zonulin, with a particular focus on gut permeability tied into the presence of coeliac (celiac) disease as per this article* and write-up.

Ever since then, zonulin has just been making wave** (full-text) after wave*** (full-text) after wave**** as per its 'disassembly' activity when it comes to TJs. The initial link with coeliac disease is an interesting one given that later work suggested that gluten, or rather the gliadin fraction of gluten, has the propensity to induce zonulin release***** (at least under certain laboratory conditions).

But coeliac disease was just the starting point for zonulin, as more recent research has suggested a potential role for this protein in relation to gut permeability in type-1 diabetes (here and here), obesity (here) and potentially quite a few other conditions (here) with a specific focus on autoimmune conditions. General Zod? No, General Zonulin.

Accepting that there still remains some work to do on zonulin with regards to the methods and mode of action of zonulin on gut permeability******* this is a very interesting protein.

With my 'wondering' hat on, I have a few questions:

• Assuming the link between type-1 diabetes, gut permeability and zonulin holds up, does this mean that a gluten-free diet might be 'advantageous' for at least some people with type-1 diabetes? I'm thinking about this recent case study******* as a template. I would also add that no medical advice is given or intended by  this question.
• Gut hyperpermeability, leaky gut, has been documented in other conditions including one close to my research heart, autism spectrum conditions (see here). Again noting the suggestions by de Magistris and colleagues (here) on how a gluten- & casein-free diet seemed to affect measures of gut permeability in their cohort, is it perhaps time to look at zonulin with regards to conditions like autism? How about schizophrenia also? 
• Finally(!), the amino acid glutamine and its proposed tie up with gut permeability. Might glutamine affect zonulin production or even the other way around? Or am I just confusing things and heading out a step too far? 

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* Fasano A. et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000; 355: 1518-1519.

** Wang W. et al. Human zonulin, a potential modulator of intestinal tight junctions. Journal of Cell Science. 2000; 113: 4435-4440.


*** Fasano A. Intestinal zonulin: open sesame! Gut. 2001; 49: 159-162.


**** El Asmar R. et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002; 123: 1607-1615.


***** Clemente MG. et al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003; 52: 218-223.


****** Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences. 2012; 1258: 25-33.


******* Sildorf SM. et al. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Reports. June 2012

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Coeliac disease as a model of autoimmunity

A very short post primarily to link to a recent paper by Kumar and colleagues* (full-text, at least for the moment).

The paper is a sort of 'all you ever wanted to know about coeliac / celiac disease but were afraid to ask' type piece and jolly informative in terms of what we think we know so far about the condition regarding genes, heritability, biochemistry and the like.

Just for good measure, here also are a few other links to some interesting discussions appearing in Nature recently on our gut microbiota and the Barker hypothesis. All I will say is 'all hail our gut bacteria' and onwards with the epigenetic revolution.

Happy reading!

P.S. I know I have been neglecting this blog for a few weeks and apologise. I will hopefully devote more time to it as the year goes on. In the meantime, a link to a peculiar song which has been running through my mind for a few week now.. Gotye and 'Somebody that I used to know' (UK readers might have heard this as an advert for 2Day 2012 from BBC Radio 2).

* Kumar V. et al. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Seminars in Immunopathology. May 2012
DOI: 10.1007/s00281-012-0312-1

Gut microflora, coeliac disease and introducing gluten

A new paper by Sellitto and colleagues* (full-text) has been causing quite a bit of interest in certain circles. The paper as the name suggests is [partially] a 'proof of concept' study which includes several topics of interest for this blog with its focus on gut microflora (and dysbiosis), coeliac (celiac) disease (CD) and some interesting metabolomics science. The added value comes with the name Alessio Fasano as part of the authorship list.

There is quite a bit of details to this paper but in essence the aims were: (i) to characterise the changes from birth to 24 months in terms of gut bacteria to genetically at-risk of coeliac disease children as a function of early or delayed introduction of gluten to the diet, and (ii) to undertake a range of analytical methods to map such bacterial populations with the hope of further informing on any relationship between gut bacteria and coeliac disease.

The paper is full-text but a quick summary of proceedings and findings:

• Forty-seven infants who had one parent with biopsy-proven CD were initially recruited before weaning had commenced. All were breastfed from birth to at least 6 months of age. From 6-12 months of age, 30 infants positive for either the HLA DQ2 and/or HLA DQ8 genotypes were randomly allocated to either a gluten-free - delayed gluten exposure - group (n=13) or a gluten load - early exposure - group (n=17).
• A smaller number of children from each group (n=8 each) were selected randomly for the analytical side of the study (which is what this paper in essence reports) where stool samples were collected at various points over the study period ranging from 7 days in to 24 months.
• The results: none of the 8 infants from the delayed gluten exposure group developed CD over the course of the study. One of the 8 infants in the early gluten introduction group did go on to develop CD at 2 years of age as measured by various serological panels and went on to a gluten-free diet with a remission of serology at follow-up.
• When levels of anti-gliadin antibodies (AGA) (IgG) were examined and corrected for gluten exposure time, the early gluten introduction group showed a higher number of IgG-AGA positive results than the delayed exposure group. The authors discuss how AGA is not necessarily a particularly good measure of CD but could indicate greater levels of intestinal hyperpermeability (leaky gut) as a result of exposure to the gliadin fraction of the gluten protein in the same way that IgG levels have been interpreted in other studies (see Sutterella and autism post). 
• Pyrosequencing of the various species and families of bacteria present across the groups at different time frames suggested some interesting goings-on. To quote: "the GI tract microbiota in DQ2+/DQ8+ infants appears to be lacking significant numbers of member of the phylum Bacteroidetes". That and a higher abundance of Firmicutes, implies that maturationally, the gut microflora of children at elevated risk of CD is different from lower risk groups as determined by comparison with an external dataset** (full-text).
• The application of 1H-Nuclear Magnetic Resonance Spectroscopy (NMR) to proceedings added that metabolomic touch as "..SCFA succinate, acetate, propionate and butyrate are found in the feces" following the introduction of solid foods. Having said that little distinguishing data was found to categorise the two groups in any significant, universal way.

It's taken me a while to get my head around all the findings from this recent paper because there was a lot of data produced bearing in mind the small participant group and preliminary status of the paper. One of the first things that did strike me is the overlap in these findings and some fairly recent data published looking at carbohydrate metabolism and autism included in this post. Decreasing Bacteriodetes and increasing Firmicutes was the preliminary finding from Williams and colleagues*** bearing in mind the difference in samples being analysed and the lack of data on HLA DQ2 / HLA DQ8 genotype provided in the group with autism being studied. I'm not going to say too much more of this 'similarity' aside from the fact that screening for coeliac disease and/or excessive intestinal permeability perhaps ought to be much more commonly undertaken in cases of autism spectrum conditions just to rule them out.

Quite a few mentions of the word 'dysbiosis' are also recorded in the current paper which reaffirms the possibility of a connection between the various populations of bacteria that reside within us and our potential risk of disease. I like the idea that this study looked at both the metabolomic and genomic side of things even if it was just based on the HLA DQ geneotypes.

So from the starting point of a genetic susceptibility to gluten, we have preliminary data on functional changes to the microbiome in susceptible people and some interesting tools for looking at how this might be expressed functionally. I look forward to more studies of this type with greater participant numbers, and in particular how such findings might extend into other autoimmune conditions and even beyond just somatic presentation.

* Sellitto M. et al. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS ONE. March 2012
DOI: 10.1371/journal.pone.0033387

** Palmer C. et al. Development of the human infant intestinal microbiota. PLoS Biology. 2007; 5:e177
DOI: 10.1371/journal.pbio.0050177

*** Williams B. et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS ONE. September 2011.
DOI: 10.1371/journal.pone.0024585

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

Diagnosis by gut bacteria?

Please don't take the title of this post too literally. Sciences is only just beginning to unravel the first strands of the complicated universe that is our gut microbiota but two recent papers certainly do make for some interesting reading.

The first paper by Iebba and colleagues* provides quite a nice summary of where we stand (research-wise) with regards to different bacterial species seemingly predominating in different childhood conditions. The second paper by Jeffery and colleagues** details the intriguing possibility that irritable bowel syndrome (IBS), or some phenotypes of IBS based on the presence of functional bowel disturbances, might be classifiable by the predominating types of gut bacteria.

The Iebba paper was of double (triple) interest to me because it mentioned autism, coeliac disease (CD) and inflammatory bowel disease (IBD) in the same sentence. In particular, the prevalence of Bacteroidetes alongside a parallel decrease of Firmicutes was a commonality between these three conditions; the first time I've seen a research group looking (bacterially) at these conditions together. I have to point out that autism is an extremely heterogeneous condition with quite a lot of scope for comorbidity; hence I am careful with any generalisations.

By contrast the Jeffery paper, although based on quite a small participant group, suggested quite a few things including that cluster analysis might be able to 'pick out' those cases of IBS associated with diarrhoea compared with those where constipation or alternating bowel habits were more common. Interestingly, their analysis also reported the opposite trend in terms of an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa in some of their participant cases. This alongside other related findings which perhaps indicate that the so-called 'leaky gut' (gut hyperpermeability) might also show some differences in terms of site when sub-categorising IBS on the basis of predominant functional bowel patterns.

Aside from factors such as different ages, different populations, different genders, et al, all of this makes me wonder about things like the immune system differences between conditions like IBD and CD compared with IBS. Indeed a few open questions: do the gut bacteria findings in autism perhaps reflect similar immune features to CD and IBD or is it all merely a coincidence? Is IBS an immune-mediated condition the same way as CD or IBD are or are other forces at work?

Without getting too Arthur C. Clarke, there are lots of potential possibilities to these collected works based on our individual and collected patterns of gut microbiota. Unlike fingerprints or retinal scans, gut bacteria is perhaps slightly more dynamic as a function of diet, environment, etc. and so is probably not going to be biometrically encoded onto your passport any time soon. Having said that, if the subtle differences between our gut bacteria might also be reflective of our condition or disease, this could potentially offer some quite startling insights into the way medicine diagnoses and also manages a wide variety of conditions.

Finally, this is probably my last post on this blog until the New Year. I would like to wish readers Merry Christmas and a Happy New Year. I raise a glass of water to your good digestive health over the holiday period!

* Iebba V. et al. Gut microbiota and pediatric disease. Digestive Diseases. December 2011.

** Jeffery IB. et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. December 2011.

The emergency exits are here and here

The title of this post has very little to do with steward / stewardess instructions delivered just before take-off, despite my recently watching the very funny Walliams/Lucas series 'Come Fly With Me'. Rather, with a straight face, I refer to your route into the world and whether Mother Nature required a helping hand in bringing you from the comfort of your watery cocoon into the real world. Could your route of entry alter your risk of developing certain things in later life... say coeliac (celiac) disease?

I am going to keep this post brief because this is a question that I have tackled before on a sister blog post: caesarean section and coeliac disease? The crux of that entry was the emerging suggestion that people born via caesarean section (c-section) were at greater risk of coeliac disease than those who were pushed through the bacteria-filled birth canal.

Further evidence has now emerged concerning a possible relationship in this paper by Marild and colleagues*. The details summarised:

• A case-control study where recorded pregnancy information was collected via a central database between 1973 and 2008.
• Biopsy-verified coeliac disease (CD) was determined for 11,749 participants compared with 53,887 age- and gender-matched non-CD general population controls.
• There was a positive significant association between elective c-section delivery and later CD diagnosis (p=0.005) but none for emergency c-sections.
• Small for dates babies were over 20% more likely to develop CD also.
• No other pregnancy variables showed an association with CD.

I quote from the author's final sentence of their abstract: ".. consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease".

I must point out that whilst bacterial colonisation of the infant gut may be a variable in determining your risk of CD, it is most probably not the only important variable. I don't want anyone reading this entry and taking it to their healthcare provider as 'proof' of anything; it is not. Likewise I am not trying to overturn any 'too posh to push' arguments.

What however can be inferred from this paper is that there may consequences to every action; some consequence might be positive (such as getting a breech presenting infant out of mum and avoiding any very serious complications), some of them might be not-so positive. The trick is to see where this research leads and, just a suggestion, whether an early bacterial 'transplant' from mum to baby one day becomes the norm for those babies who don't end up traversing the birth canal. Just a suggestion.

* Marild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. October 2011.

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.

Parasitic infection, coeliac disease and inflammation

My day-to-day job does not normally include giving lectures and presentations but today was an exception. I was asked to give a short talk on autism, and specifically some of the more 'somatic' research aspects to the condition. One of the issues that cropped up during that talk was some discussion on how we might think that we are in charge of our behaviour, but more often than not external environmental forces might also influence us. By environment, I mean the physical environment we can see and interact with but also the more hidden aspects. Words like Toxoplasma gondii and schizophrenia were used as examples, but also some speculative suggestions about how other 'parasitic' infections might affect our health and wellbeing.

Such discussion brings me neatly to a recent paper by Henry McSorley and colleagues from Australia published in PLoS ONE. The crux of the paper (which is open-access) is that purposeful infection with hookworm might have some interesting positive effects on various aspects of inflammation in relation to coeliac (celiac) disease (CD).

I must admit that I have covered parasitic infection in a previous post on autism (here); the conclusion being that our modern-day obsession with hygiene leads to the eradication of certain parasitic species which have evolved alongside us, and with it, a suggested increase in things like inflammation and conditions manifesting inflammation.

It does appear that similar findings were reported by McSorley and colleagues, where:

• A 2-stage clinical trial was undertaken. Trial 1: 20 participants in total with CD and on a gluten-free diet; 10 were randomly infected with the larvae of the hookworm (Necator americanus) administered via the skin, the controls were given topically administered chilli pepper. At 20 weeks post-infection (with a top-up at 5 weeks), a gluten-challenge was given. Trial 2: a follow-up control participants, infecting 7 of them with hookworm, top-up infection and gluten challenge.
• Levels of duodenal interferon-gamma (IF-y) (sorry about the lack of Greek gamma symbols) and the cytokine IL-17A were significantly decreased in the hookworm infected group from Trial 1 post gluten challenge. This and other results led the authors to assume that helminth therapy might skew the immune response in CD towards a Th2 phenotype; in effect, a more anti-inflammatory response (see this article for a better description of Th1 and Th2).

I must point out that I am in no way advocating such parasite therapy for anyone. I am also under no illusion that these results suggest a simple relationship between parasite and inflammation because they do not. I am however drawn (again!) to the notion that such parasites might carry some important evolutionary function for human health and as such, our recent leanings towards cleanliness (next to Godliness apparently) and sterility might just be to the detriment of our health.

* McSorley HJ. et al. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. 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.

Coeliac disease in Type 1 diabetes

When I think of coeliac (celiac) disease and the various names attached to research on this exquisite sensitivity to gluten, I think of a few names with a good publishing track record in this area. First name out of the hat is Mario Hadjivassiliou. Second is David Sanders. Without turning this post into some idol worship, when I see new papers appearing from one or other of these guys, my interest is piqued.

So when this paper from Leeds and colleagues* appeared bearing both names on the author group, I was interested. When I saw that the paper was also looking at another autoimmune condition, type-1 diabetes alongside coeliac disease (CD), I was even more interested.

The main facts from the Leeds case-control study are:

• The prevalence of CD in their cohort of people with type-1 diabetes was 3.3%. Although there is still some debate about prevalence of CD in the general population, it is generally accepted to be currently around 1%. Interestingly, 3.3% is exactly the prevalence of CD in cases of autism described in this paper from a few years back. What a coincidence. 
• At diagnosis of CD, type-1 diabetes seemed to be associated with a higher prevalence of retinopathy, nephropathy and peripheral neuropathy. Some of these conditions have been noted in 'gluten sensitivity' alone.
• Glycemic control was also worse in the diabetes-CD group, accompanied by lower HDL (good guy) and total cholesterol.
• A gluten-free diet is generally well tolerated by individuals with CD and comorbid type-1 diabetes. 

I am excited by this research. Excited because as well as linking two autoimmune conditions, the genetics of which are starting to receive some attention, it extends into some other areas already discussed on this blog that may affect quality of life and importantly, longevity.

* Leeds JS. et al. High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care. September 2011.

Metabolic syndrome and gluten

I am pretty used to hearing about and using the word 'metabolic' in my day-to-day work. In this context, metabolic refers to a few things: a metabolic pathway, describing some chemical reactions leading to an end compound or other endpoint process; or an in-born error of metabolism, describing some genetic 'malfunction' predominantly with enzymes or enzymatic reactions.

A new term has started to creep into my dictionary over the past few months or so, metabolic syndrome. Whilst sounding like it should have something to do with the other uses I described, metabolic syndrome actually describes a set of risk factors which might predispose a person to subsequent problems of coronary artery disease, stroke and type-2 diabetes. The main risks taken from the various descriptions tend to include:

• elevated central obesity (your waist measurement above a certain threshold)
• dyslipidemia (abnormal levels of cholesterol or fat in blood)
• hypertension (elevated blood pressure)
• elevated fasting plasma glucose levels

Why might metabolic syndrome be important to this blog? Well, because of this paper by Garcia-Manzanares and colleagues* published in the World Journal of Gastrointestinal Pathophysiology which reported on a case study of a woman presenting with the features of metabolic syndrome alongside coeliac (celiac) disease, and what happened when a gluten-free (GF) diet was installed.

I am sure that readers can guess what I am going to say. The woman, who was overweight, presented with high cholesterol and triglycerides, alongside iron deficiency was eventually found to present with comorbid metabolic syndrome and coeliac disease. Installation of a GF diet seemed to solve the iron problems (as one would expect it would in coeliac disease) but also seemed to positively affect dyslipidemia and measured glucose levels. In short, some of her metabolic disease risk factors seemed to be reduced.

It would of course be easy to say that all the effects were from the GF diet (and indeed I might try and further that view) but stepping back there are quite a few potential confounders which might also have played a hand in the results. So things like the fact that entering onto a GF diet probably quite fundamentally changed her diet anyway; out goes the wheat and other gluten-containing grains yes, but in comes perhaps more protein, more vegetables and fruits, more dairy products? What about any additional supplementation for all those vitamins and minerals that might be lost from the diet? I dare say that she was also told to do a little more exercise to help reduce her weight burden also. Lots of confounders which could potentially affect her metabolic disease risk factors.

Having said all that, there has for quite a while, been some discussions about how a GF diet might potentially be linked to lots of different things outside of just managing coeliac disease and other gluten sensitivities. I am not going to go down the autism or schizophrenia route too much, but there are some suggestions of potential effects in these areas and for related conditions particularly the health effects of components of our modern diet such as carbohydrates and what happens when you reduce the carbs. Another quite interesting thought (as least to me!) is whether or not the link between gluten removal and subsequent altered gut permeability in coeliac disease might also tie into some of the effects noted. So does a better gut barrier function promote better lipid and glucose measures?

I am going to stop there as I fast approach the limits of my competence in an area which is screaming out for further investigation. I state my disclaimer that I am not providing any medical or dietary advice from the research discussed in this post - that's the job of your healthcare professional, and I strongly suggest you consult them before making any changes to diet or anything else.

* Garcia-Manzanares A. et al. Resolution of metabolic syndrome after following a gluten-free diet in an adult woman diagnosed with celiac disease. World Journal of Gastrointestinal Pathophysiology. June 2011.

Milk, gut bacteria and coeliac disease

Coeliac disease (CD), that exquisite sensitivity to dietary gluten, has long been the focus of quite a bit of research. That's not to say that in all those years we don't know a little bit about CD; some of its genetics, its diagnostic markers, its treatment, but there are still lots of things we don't know about CD as well as the various non-coeliac forms of gluten sensitivity which seem to be emerging.

When it comes to early markers or risk factors for CD, there are quite a few already in the research literature. I covered some of them on one of the sister blogs (here and here). Indeed the last link including this paper on your choice of entry into the world and subsequent gut bacteria, provides a good example of what might affect your start-up gut bacteria and potentially your subsequent risk of things like CD on the back of my previous post.

Enter a new potential player into the world of CD risk; surprisingly enough from your earliest form of nourishment post-partum, milk. The research by Sanchez and colleagues* postulated a connection between the genetic risk of CD and the type of bacteria from the Bacteroides species identified in fecal samples from infants with a parent with CD. An overview of the results can be found here.

The results from this study point towards two important points:

• Genetic risk of CD as measured by the HLA-DQ genotype might influence the composition of the gut bacteria.
• The type of early feeding practices (breast vs. bottle) might also influence gut bacterial composition at different times of infancy.

Whilst there are some interesting links made in this and other studies in this area, as always we need to be cautious in jumping to conclusions. Several authors have speculated that the type of early feeding pattern might alter the risk of developing CD. The evidence is however far from conclusive; indeed whilst there may be some effect in delaying the onset of CD, delay does not mean the condition will not develop. Indeed we will have to wait for studies like this one to formally reports before we can draw any firmer conclusions.

Still what studies like this offer is an insight into the complicated world of genetics and environment in conditions like CD and how our gut bacteria might well be king-maker (or at least a prince/princess) when it comes to conferring risk and protection against lots of conditions.

* Sanchez E. et al. Influence of environment and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species. Applied & Environmental Microbiology. August 2011.