Friday, 2 November 2012

That recent metabolomics study on autism (part 2)

Consider this a part-two to my previous post introducing the paper from Dr Xue Ming and colleagues* on metabolomics, amino acids and gut bacteria with autism in mind. It's going to be another micropost (sort of!) given that quite a bit of the background has already been discussed previously.

So straight to the paper:

  • As expected, the study from Yap and colleagues** (including Prof. Nicholson) was the template for undertaking this study.
  • Spot urine samples were collected from 48 children diagnosed with DSM-IV autism; in some cases confirmed by the gold-standards that are ADOS and ADI, and compared with 53 matched asymptomatic controls.
  • Alongside the various screening measures, a gastrointestinal [disorder] GI severity scale was used to ascertain the presence of GI dysfunction. (verified in 29/48 children with autism).
  • Mass spectrometric analysis of the urine sample, blah, blah, blah, and out of a total of 391 metabolites, confirmed metabolites, located in samples, 82 of them were altered between autism and control samples.
  • Amino acids et al: several amino acids were significantly lower in the autism group including glycine, serine and the alanines. Taurine also featured. Indeed quite a few of the gamma glutamyl amino acids were also reduced in the autism group with a link to GI disorders potentially suggestive of issues with gamma glutamyl transpeptidase.
  • Gut bacterial metabolites: some really interesting stuff here and very much influenced by the presence of GI problems or not. Of particular note, "significantly increased levels of 2-(4-hydroxyphenyl)propionate and taurocholenate sulfate" and reduced levels of 3-(3-hydroxyphenyl)propionate and 5-aminovalerate.
  • Mention is also made of some of the gut bacterial findings previously made with autism in mind, and even the possibility of gut hyperpermeability (leaky gut) as influencing the absorption of metabolites. Think back to Paul Patterson' recent announcement on mice, leaky gut and gut bacteria.

A couple of quick observations. Taurine: OK, more an organic acid than an amino acid. Found to be significantly lower in the autism group results compared with controls in this study, but by contrast, elevated in the Yap study. One could argue that there were participant geographical differences (Ming: USA vs. Yap: Australian/Swiss) which might reflect genetic, dietary or environmental differences across different geographical groups. It's interesting to note also that in the Yap paper they noted that "taurine concentrations were hypervariable in the autism group". That and the differences across analytical technologies (Ming: mass spec vs. Yap: NMR). Autisms not autism? Who knows?

Lower urinary glycine and indeed N-acetylglycine were also picked up in the autism group of the Ming study. I don't want to make too much of this at the moment but perhaps will throw in two possibly relevant things: (a) that very interesting paper from Andrew Clayton on autism, aromatic amino acids and gut bacteria (see this post) which talked about benzoic acid and hippuric acid and the link with glycine and (b) the very interesting area of glycine and sleep (see this post). I'm not making any value judgements bearing in mind the focus on urinary glycine not plasma levels of glycine, so just putting it out there.

There's not too much more to say on the the Ming paper apart from being a really interesting piece of research and with a strong requirement for independent scientific replication. That and given the focus on comorbid GI conditions appearing alongside some cases of autism, perhaps a lot more inspection into the root causes and management of them. Indeed look no further than the special Pediatrics supplement on autism for quite an interesting opinion paper*** on this topic with some pretty big hitters as part of the authorship group.

And rest.


* Ming X. et al. Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res. October 2012.

** Yap IK. et al. Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res. 2010; 9: 2996-3004.

*** Coury DL. et al. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics. 2012; 130: S160-S168.

---------- Ming X, Stein TP, Barnes V, Rhodes N, & Guo L (2012). Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study. Journal of proteome research PMID: 23106572