Yap, Angley, Veselkov, Holmes, Lindon, and Nicholson (2010) have ignited a lightning storm of interest with their theoretical urine test for autism that could prevent autism, at least according to study author Nicholson, speaking to Richard Alleyne of the Telegraph:

"Professor Jeremy Nicholson, the author of the study, said: "Children with autism have very unusual gut microbes which we can test for before the full blown symptoms of the disease come through.

'If that is the case then it might become a preventable disease.'"

Yap et al. write that “Autism has been shown to have strong associations with various metabolic abnormalities, immunological function and gastrointestinal disturbances, although their mechanistic significance is unknown.5–8”

Let’s look at their sources for the idea that children with autism have intestinal issues that are causal for said autism, since this is outside mainstream scientific findings (Ibrahim et al., 2009; Buie et al., 2010), especially in light of Nicholson’s whole gut microbe bit.

(5) Kidd, P. M. Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base. Altern. Med. Rev. 2002, 7 (4), 292–316.

So, one source for this whole gut microbe difference is from a journal entitled Alternative Medicine Review. And Kidd (2002) has this to say about autism:

“Frequent vaccinations with live virus and toxic mercurial content (thimerosal) are a plausible etiologic factor.”

So, Yap et al. used a dubious source with outdated information regarding a debunked thimerosal connection with autism? Really?

Moving on.

(6) Ashwood, P.; Anthony, A.; Pellicer, A. A.; Torrente, F.; Walker-Smith, J. A.; Wakefield, A. J. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J. Clin. Immunol. 2003, 23 (6), 504–17.

Okay, so in spite of all the controversy surrounding Walker-Smith and Wakefield, Yap et al. used a 2003 journal article by them for their gut theory?

Yeah, kinda lessons the legitimacy, doesn’t it?

Moving on:

(7) Chugani, D. C.; Sundram, B. S.; Behen, M.; Lee, M. L.; Moore, G. J. Evidence of altered energy metabolism in autistic children. Prog. Neuropsychopharmacol. Biol. Psychiatry 1999, 23 (4), 635–41.

1999? And it’s a pilot, with 9 to 15 autistic children in it. Hardly definitive and has nothing to do with gut microbes whatsoever or with gastrointestinal issues or differences.

Let’s look at the last study Yap et al., and especially Nicholson, seem to be using to hang their hat on the gut differences theory.

(8) Levy, S. E.; Souders, M. C.; Ittenbach, R. F.; Giarelli, E.; Mulberg, A. E.; Pinto-Martin, J. A. Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders. Biol. Psychiatry 2007, 61 (4), 492–7.

Of all the sources, this perhaps is closest to being credible except for the fact that there are more recent, more exhaustive studies that discount there being more gastrointestinal issues in autistic individuals than the general population (Ibrahim et al., 2009; Buie etal., 2010). There’s a problem, though, even with this study in that it uses Wakefield’s retracted Lancet case series as one of its backbones.

In other words, Yap et al., despite the opportunity to be aware of the weakness of their sources, good mainstream science countering those sources, chose to use dubious sources as the backbone for their theory regarding “gut disturbances.”

Let’s say we ignore all the above and look at the actual science conducted by Yap et al. and contrast it to what Nicholson says in the Telegraph article.

Who did the researchers look at? Yap et al. report that they used “34 controls, 28 siblings and 39 autistic urine samples.” The controls came from the Swiss Tropical Institute, and the autistic and siblings were from Australia. But the researchers assure readers that they made sure there was no difference: “To address bias deriving from geographical location, urine samples from the second group of controls were profiled together with the first group of controls. The two control data sets were shown to be statistically indistinguishable (data not shown).”

Okay, so this is an extremely small sample. It’s a new theory, so qualifies as a pilot investigation. Surely the researchers recognize that and don’t hype it past a “hey, isn’t this interesting?” kind of level, right? Wrong.

Let’s just replay Nicholson’s quote again:

"Professor Jeremy Nicholson, the author of the study, said: "Children with autism have    very  unusual gut microbes which we can test for before the full blown symptoms of the disease come through.

'If that is the case then it might become a preventable disease.'"

There is no indication of how these study participants were selected, there’s no mention of differences in diet that would contribute to differences.

In addition, Nicholson with his five pound urine test to diagnose autism as early as six months and thereby prevent it goes much farther than the study itself does. And Alleyne certainly goes well beyond it:

“Eventually the link between the learning difficulties and the gut microbes could be established and that could lead to "probiotic" treatments or cures.”

There is an abundance of evidence that gastrointestinal issues are not causative or correlated with autism (Ibrahim et al., Buie et al.).

There is no reason despite 34 autistic children (whose selection criteria is not visible) having different urine results to believe what Nicholson is asserting in his interview with Alleyne. Yap et al. didn’t call for using the urine test to diagnose early, but noted that further, larger studies needed to be done. Certainly, relying on sound scientific data for one’s theories is important and it is not clear, based on the four studies the authors rely on for their assumption of a gastrointestinal link with autism, that they are on solid ground.

Nicholson, at least as presented by Alleyne, did not speak as a circumspect scientist with preliminary data from a small sample, would or should.

Alleyne, as a member of the media, went too far in asserting “The latest breakthrough shows that it is possible to distinguish between autistic and non-autistic children by looking at the by-products of gut bacteria and the body's digestive processes in the children's urine.” No, that’s not what this study showed. It showed that the three groups were different, but it didn’t show why and it didn’t rule out sample selection bias.


(Buie et al., 2010). Buie, Timothy, Campbell, Daniel B., Fuchs, George J., III, Furuta, Glenn T., Levy, Joseph, VandeWater, Judy, Whitaker, Agnes H., Atkins, Dan, Bauman, Margaret L., Beaudet, Arthur L., Carr, Edward G., Gershon, Michael D., Hyman, Susan L., Jirapinyo, Pipop, Jyonouchi, Harumi, Kooros, Koorosh, Kushak, Rafail, Levitt, Pat, Levy, Susan E., Lewis, Jeffery D., Murray, Katherine F., Natowicz, Marvin R., Sabra, Aderbal, Wershil, Barry K., Weston, Sharon C., Zeltzer, Lonnie, Winter, Harland. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report Pediatrics 2010 125: S1-S18

(Ibrahim et al., 2009) Samar H. Ibrahim, Robert G. Voigt, Slavica K. Katusic, Amy L. Weaver, and William J. Barbaresi Incidence of Gastrointestinal Symptoms in Children With Autism: A Population-Based Study Pediatrics, Aug 2009; 124: 680 - 686

(Yap et al., 2010). Ivan K. S. Yap, Manya Angley, Kirill A. Veselkov, Elaine Holmes, John C. Lindon and Jeremy K. Nicholson Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls J. Proteome Res., 2010, 9 (6), pp 2996–3004 Publication Date (Web): March 25, 2010 (Article) DOI: 10.1021/pr901188e