Tuesday, 17 December 2013

Gut permeability in teens with autism and SEN

Naturally I was going to be interested in the findings of Neil Dalton and colleagues* comparing a measure of gut permeability in teenagers (well, those aged 10-14 years old) diagnosed with an autism spectrum disorder (ASD) (n=103) and those with special educational needs (SEN) (n=30).

Regular readers are probably well used to some of my discussions on the possibility of a triad of issues - gut permeability, gut bacteria and immune function - being related to cases of autism. Indeed not so long ago I posted a sort of 'where is research up to' with gut permeability in relation to autism (see here). Already in light of the recent Patterson lab findings on leaky mice guts and immune activation (see here) this megapost is out of date. And now with the Dalton findings it's even more out of date, such is the rapidity of scientific research (and the responsiveness of blogging).

Anyhow, back to the Dalton findings. Well, I've got to really start with a quote from their study: "no statistically significant group difference in small intestine permeability in a population cohort-derived group of children with ASD compared with a control group with SEN". This was based on quite a nice participant number of teens (yes, I'll mention that again) where gut permeability was "assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry-mass spectrometry". That mass spectrometry (MS) mention adds some significant credibility to the detection methods used to assay for those markers of intestinal permeability.

That being said, the devil is in the detail when it comes to the study findings outside the group comparisons between autism and SEN participants. So: "Eleven children (9/103 = 8.7% ASD and 2/30 = 6.7% SEN) had L/M recovery ratio > 0.03". L/M recovery ratios refers to the amount of lactulose and mannitol sugars recovered in urine generally suggested to be below 0.03 to be a 'normal' result (see here). In effect, 8.7% of the children with autism in the Dalton cohort presented with leaky gut.

I have to say that I am a little bit surprised by the Dalton results and how much they contrast with the other work in this area particularly the de Magistris findings** in terms of the percentage of children showing abnormal gut permeability (36% vs. 8%). One might assume that there are potential population differences (UK vs. Italy) or that even age at gut permeability analysis might be an issues. Realising that use of a gluten- and casein-free (GFCF) diet also seems to impact on gut permeability issues (as was perhaps the cases when considering the Robertson paper***) is another potential place to look for reasons for the disparity across the results. If I also had to ask one further thing about the Dalton paper, it would be to have included a typically-developing group alongside their autism and SEN cohorts so we could frame the results with previous data.

In terms of the publication team and very possibly the cohort used for this study, I'm not altogether sure but I think we might have already heard something about these participants insofar as that 'functional bowel problems do seem to be present in autism' work published by Chandler and colleagues earlier this year (see here). I base that on the single result of a participant with autism showing a result representative of "more definitely pathological" gut hyperpermeability (leaky gut) and being subsequently presenting with "undiagnosed asymptomatic celiac disease". Indeed, 1 out of 103 teens with autism presenting with autism is not a dissimilar figure from other work****; bearing in mind the Ludvigsson paper on 'not quite coeliac disease' but something else being potentially related to autism (see here).

So, yet again, more data suggesting that when it comes to gut permeability, autism (at least some cases of autism) is much more deserving of further inquiry. That also 6.7% of the small participant group with SEN also showed potential issues with a leaky gut might also be an important area of future investigation.

Now about zonulin - any takers for a study on that molecule and autism?

[Update: January 2014. Thanks to the wonder that is PubMed Commons, I've transmitted some of my thoughts on this paper to the PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/24339339].

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* Dalton N. et al. Gut Permeability in Autism Spectrum Disorders. Autism Research. 2013. Dec 12. 10.1002/aur.1350

** 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 Oct;51(4):418-24.

*** Robertson MA. et al. Intestinal permeability and glucagon-like peptide-2 in children with autism: a controlled pilot study. J Autism Dev Disord. 2008 Jul;38(6):1066-71.

**** Batista IC. et al. Autism spectrum disorder and celiac disease: no evidence for a link. Arq Neuropsiquiatr. 2012 Jan;70(1):28-33.

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ResearchBlogging.org Neil Dalton, Susie Chandler, Charles Turner, Tony Charman, Andrew Pickles, Tom Loucas, Emily Simonoff, Peter Sullivan, & Gillian Baird (2013). Gut Permeability in Autism Spectrum Disorders Autism Research DOI: 10.1002/aur.1350