Friday, 30 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.

Thursday, 22 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.

Wednesday, 14 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.

Thursday, 1 September 2011

The gut virome

Our gastrointestinal tract is alive. Teaming with all sort of weird and wonderful compounds and organisms, it truly is a world within a world. Metabolites from food, various neurotransmitters, digestive juices and enzymes; all swimming merrily around doing things which we have only started to understand, not just in the gut but also connected to lots of other systems in the body.

Our gastrointestinal bacteria constitutes a large portion of this 'biochemical soup' and has started to receive quite a lot more research inquiry recently as a result. What is perhaps only now starting to be realised is that our gut also house a lot more than just bacteria, it is also home to quite a few viruses also.

Think viruses and people automatically assume infection and bad things like bird flu. Even today, alerts are cropping up suggesting that bird flu might be making a comeback and this time with even more lethal strains. Viruses do not have a great reputation despite the fact that perhaps not all are the devil incarnate as exemplified by this recent advance in a potential anti-cancer virus.

A recent paper by Minot and colleagues* published in Genome Research suggests that our gut might house quite a few viruses and that what we eat has the potential to affect both the bacterial and viral signature in our gut.

The paper which has been summarised here suggests the gut virome, similar to the gut bacterial microbiome is both unique to a person and dynamic; in this case, changing the fibre and fat content of a persons diet resulted in changes to the gut virome.

I await more investigation on this topic. Investigation into how our gut virome interacts with our health and disease and how potentially other environmental factors might affect our viral world within a world.

* Minot S. The human gut virome: inter-individual variation and dynamic response to diet. Genome Research. August 2011.