Wednesday, 4 January 2017

A distinctive microbial signature in kids with autism and GI issues?

"Our findings identify distinctive mucosal microbial signatures in ASD [autism spectrum disorder] children with FGID [functional gastrointestinal disorders] that correlate with cytokine and tryptophan homeostasis."

So said the study results published by Ruth Ann Luna and colleagues [1] who "compared mucosa-associated microbial communities in children with ASD to previous reports characterizing stool in this population" among other things. If you are eating breakfast/lunch/dinner at the time of reading this post, maybe give it a few minutes before reading on...

So rectal biopsies and blood specimens were the samples under investigation and the focus was very much on those children on and off the autism spectrum who also presented with various functional bowel issues. Just before anyone starts to question the ethics of taking biopsies and the like, the authors expand by reporting that participants were "undergoing a lower endoscopy for one of the following symptoms: abdominal pain, altered stool patterns, or painless bright red blood per rectum." In these days of health inequality attached to the label of autism (see here for an example), these were children who were being investigated for their bowel issues and not being unnecessarily subjected to such invasive techniques just for the sake of science.

The various analyses undertaken on those blood and biopsy samples were pretty wide-ranging. Bacterial species present in mucosal samples and their supernatants were included but so researchers also looked at cytokines (various chemical markers linked to immune function among other things) in blood samples and supernatants and levels of "serotonergic metabolites" (chemicals related to the aromatic amino acid tryptophan) pertinent to their "microbiome-neuroimmune signatures" hypothesis testing. Bear in mind that when it comes to the neurotransmitter called serotonin (5-HT), the gut truly is the second brain.

Results: taking into account the relatively small participant numbers included for study - "ASD children with functional GI disorders (ASD-FGID, n=14), as compared to neurotypical (NT) children with (NT-FGID, n=15) and without abdominal pain (NT, n=6)" - there were some interesting, if not unexpected, results to be seen. "Principal component analysis showed clear separation between the ASD-FGID group and the NT-FGID and NT groups" on the basis of the bacterial communities present in those mucosal samples. In the autism group, several mucosa-associated Clostridiales species were predominant as per that noted in other independent findings (see here). Interestingly authors also observed "marked decreases in Dorea and Blautia, as well as Sutterella" species perhaps contrasting with other research in this area (see here). I'll let readers trawl through the other bacterial families talked about in the paper including those potentially linked to the presence of specific functional bowel states derived from questionnaire data from participants.

Looking at any potential associations between mucosal bacterial communities, cytokines and those tryptophan metabolites, researchers also reported some important, if preliminary, observations. So: "Group comparisons revealed that IL-6 [interleukin 6] and tryptophan release by mucosal biopsies was highest in ASD children with abdominal pain, whereas serotonergic metabolites were generally elevated in children with FGIDs." I'd like to see these findings replicated in larger groups before I make anymore of what their potential significance could be but it is intriguing that pain might play some hand in immune signalling and the production of amino acid metabolites. More so when one considers other related research [2].

On the back of a recent post talking about blood-based 'biomarkers' pertinent to more pathological bowel states occurring alongside cases of autism (see here) it is good to see that autism + GI issues is starting to receive a little more scientific attention. It shows that science has moved on from the question 'are bowel symptoms over-represented when it comes to autism?' (answer: yes) and actually started to look at the questions of 'why? and 'how?' The focus on gut bacteria is a worthy cause (see here) and if replicated and found to be important, opens up various intervention options derived from work in other areas of medicine (see here). Indeed, there is a 'watch this space' call for investigations looking at probiotics and autism for example (see here) with the promise of more to come [3]. Oh, and don't forget the good old 'gut-brain axis' when it comes to a possible tie-up between bowel and brain with at least some autism in mind.

But for now, autism, gut disorder, gut bacterial composition, mucosal immune function and little old tryptophan and its metabolites get some well deserved combined research attention...

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[1] Luna RA. et al. Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. CMGH Cellular and Molecular Gastroenterology and Hepatology. 2016. Dec 11.

[2] Ahmad SF. et al. Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children. Mol Immunol. 2016 Dec 24;82:57-65.

[3] Navarro F. et al. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol. 2016 Dec 14;22(46):10093-10102.

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ResearchBlogging.org Luna, R., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G., Savidge, T., & Williams, K. (2016). Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder CMGH Cellular and Molecular Gastroenterology and Hepatology DOI: 10.1016/j.jcmgh.2016.11.008