Unexpected improvement in core autism symptoms following a probiotic?

The paper by Enzo Grossi and colleagues [1] (open-access) is definitely worthy of a post today and the suggestion that the "appropriate use of probiotics" might be something to consider for at least some diagnosed as being on the autism spectrum.

Accepting that I'm slightly curious as to what would be considered 'inappropriate use of probiotics', the Grossi paper describes the clinical journey of a boy aged 12 diagnosed with an autism spectrum disorder (ASD) accompanied by learning (intellectual) disability who was concurrently diagnosed with coeliac disease (CD). The CD diagnosis was a slightly complicated affair given that whilst he presented with the relevant 'genetics' of CD (HLA genotypes) and "a slight elevation of transglutaminase antibodies" a gluten-free diet seemingly did very little in terms of clinical benefits and when it came to the "blood-specific tests for celiac disease" they were always negative. I'll come back to some of these points shortly but his chronic gastrointestinal (GI) symptoms that were first thought to be CD related were subsequently put down to irritable bowel syndrome (IBS).

In light of the IBS diagnosis and given some pretty important research suggesting that specific probiotic formulations might have treatment-potential for some IBS (see here), a probiotic intervention was prescribed: VSL#3. What happened next is intriguing...

After a few weeks of probiotic treatment, some 'apparent improvements' were noted in the boy's behavioural presentation. This led the authors to start looking more systematically at whether said improvements could be charted and possibly tied into his probiotic use. We are told that the various components of his behavioural plan that had been in place for some 6 years were continued without "any particular change." Use of the gold-standard assessment tool that is the ADOS - Autism Diagnostic Observation Schedule - was employed over a period of about a year-and-a-half to covering the period of probiotic use. Data for two ADOS assessments were available before the probiotic was installed and four assessments were carried out during and post-intervention. The results suggested that scores relevant to social affect (the DSM-5 term describing issues with social and communicative domains) changed over the intervention period in line with some of the observations made of this boy. Further: "This change was surprising since in our assessment records over several years, the patient status had remained steadily unchanged." It should also be noted that the GI symptoms, the initial target of probiotic use, also reduced "as expected."

Yes, I know that this is a case report (and N=1) and given what we (think we) know about autism, such results can by no means be generalised to all autism. There could also be a million and one other variables potentially accounting for the results including something called puberty potentially playing a role (see here) given the age of the boy. One needs to be cautious.

But... these are still potentially important results for quite a few different reasons. Going back to the description of CD being diagnosed and then un-diagnosed, regular readers might know about my interest in something called non-coeliac gluten sensitivity (NCGS) when it comes to something like autism (see here). The suggestion being that although a diagnosis of autism is not protective against a diagnosis of CD, the still emerging peer-reviewed data seems to suggest something slightly more gluten-fuzzy when it comes to at least some autism. That elevated levels of tissue transglutaminase are also not an uncommon finding in relation to [some] autism (see here) adds to the curiosity in this area.

Bowel or GI issues occurring alongside autism? Well, I've said it before and I'll say it again: GI issues (both functional and pathological) are over-represented when  it comes to autism (see here). You can call it IBS or similar other bowel related label but the fact of the matter is that such issues are not uncommon and lots more resources need to be poured into looking at and importantly, treating such issues save any further health inequalities appearing alongside the label of autism. It makes good sense that if something like IBS is diagnosed, and the various meta-analyses suggest that probiotics might be one part of an intervention strategy for IBS, their use where IBS clusters with autism should be the same as when autism is not part of the equation. Simple as.

The Grossi case report also highlights how gut and brain, with a healthy portion of gut microbiome, might show some important links for some on the autism spectrum [2]. This is by no means 'a new thing' (see here) and to some extent, justifies the various studies where gut bacteria for example, have been looked at in the context of autism (see here for example). That such a connection might also include issues with gut permeability (see here) is another important detail and is evidenced by the possibility that probiotics may also work on the gut membrane [3] as well as those trillions of wee beasties that call us home.

In short, more research on the use of probiotics with autism is very much implied (and indeed is already in progress). Watch this space.

To close, first we had Mr Pharmacist from The Fall. Now we have Oxymoronic from NOFX. Spot the difference...

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[1] Grossi E. et al. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Medical Case Reports. 2016; 4: 2050313X16666231.

[2] Inoue R. et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders. Biosci Biotechnol Biochem. 2016 Sep 1:1-9.

[3] Mennigen R. et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1140-9.

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Grossi, E., Melli, S., Dunca, D., & Terruzzi, V. (2016). Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics SAGE Open Medical Case Reports, 4 DOI: 10.1177/2050313X16666231