Gastrointestinal and microbiome changes in autism?

Tony Persico and V. Napolioni have just published a review article centered around their finding that a particular molecule, p-cresol, is excreted (found in the urine) at higher levels in autistic kids than in controls. I described their initial finding in a 5/18/12 post, but now they say that a similar finding is arising in preliminary data from a study of an independent cohort in Tours, France. Interestingly, in both patient populations the levels of this molecule are higher in female autistic kids compared to males, it is higher in the most severely affected kids, and it is higher in kids that underwent regression – loss of language and social interaction. The high levels are restricted to young kids, less than 8 years old. Why is this important/interesting? This molecule is produced in the gut by certain types of bacteria, and some of these same bacteria have been reported to be strongly increased in in the GI tract of autistic kids. At higher concentrations, p-cresol and its main metabolite can cause inflammation, which could possibly be linked to the “leaky gut” syndrome that has been reported in a major subset of autistic kids. Is this the way this molecule gets into the blood and then through the kidneys and into the urine? What causes p-cresol to go up in this subset of autistic kids in the first place? Does it affect behavior? Persico hints that it may indeed do so in preliminary animal experiments. We just submitted a paper on our mouse model of maternal immune activation that reports some related findings – stay tuned!

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5 Responses to Gastrointestinal and microbiome changes in autism?

  1. Inasy says:

    Bacteria seems to be a critical piece to the autism puzzle. The bacteria /disease connection has become a common theme. Any ideas on how one reduces p- cresol levels.
    Thank you for another great post.

  2. Thanks for the post.

    Whilst this is a potentially interesting finding, I’m taken back to some Australian research conducted by Manya Angley and colleagues on short chain fatty acid metabolism and autism: http://www.ncbi.nlm.nih.gov/pubmed/22535281
    They concluded that no elevations in p-cresol were noted in their group (bearing in mind their analysis was based on stool samples).

    That and the 2010 Yap findings: http://www.ncbi.nlm.nih.gov/pubmed/20337404 (no overall difference in urinary levels of 4-cresol sulfate) makes me wonder whether we need some definitive research in this area.

    Bear also in mind the various isomers of cresol which can (as our lab has found out!) complicate analysis and that also the original Persico findings were based solely on HPLC with UV detection (no mass spectrometry) http://www.ncbi.nlm.nih.gov/pubmed/21329489 (hence I would perhaps question exactly what they were looking at and finding).

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