The DOGMA of dysbiosis

I think it's been time enough for the initial excitement of first results from the Human Microbiome Project (HMP) to have subsided and questions like 'where next?' to be asked. Although the research possibilities are almost endless and have the potential to re-write some biochemistry textbooks, I admit that I raised a smile when seeing a post about the potential for further study of bacteria in autism research on the Simons Foundation website. This kinda spurred me on to write this post on bacteria and more specifically dysbiosis with autism in mind following on from some previous interest in this topic; that and the publication of an opinion piece* by Dr Petra Louis from the University of Aberdeen.

Dysbiosis, or DOGMA if you wish(!), describes a state of 'imbalance' with regards to the multitude of microbes which call us humans (and animals) home. I suppose one could call it a sort of bacterial homeostatic dysregulation (if that makes any sense) illustrating how we should be at one with our bacteria which seem to be able to do all manner of things aside from just aiding digestion (see here about GABA and another link to inflammation). Excuse me for a moment while I bring my bacteria into planetary alignment...

Most mention of dysbiosis in the research literature tends to focus on bacterial dysbiosis of the gut, which is where I also want to focus attention with this post. Indeed dysbiosis is finding quite a comfortable spot when it comes to the gut, gastrointestinal (GI) tract if you will, as per the links being made with conditions such as inflammatory bowel disease (here) and coeliac disease (here). Don't however be fooled into thinking that bowel-related conditions have the monopoly as per other research in alcoholic liver disease (here) and conditions related to obesity (here). The important caveat however being that establishing cause and effect from dysbiosis is not yet cut-and-dried.

Aside from the quite speculative post discussing the possible associations made between PCOS, DOGMA and autism, dysbiosis has had another mention on this blog previously as part of the excellent Brent Williams paper on carbohydrate digestion** in cases of autism and gastrointestinal symptoms. I was, and remain, excited about the Williams paper despite the small sample group and preliminary nature of the findings reported not only because of the authorship group (Buie, Bauman, Lipkin) but also because results spanned genetics, biochemistry and importantly, endophenotypes. I await further confirmatory studies with some expectation.

There is other research on dysbiosis and autism in the research literature, some of which mentions dysbiosis, others not overtly so:

• Dr Parris Kidd seemed to be ahead of the game with his two papers (here and here) which speculatively talked about dysbiosis and autism among other things. That and another paper published by Richard Blaylock (here), seemed to introduce the possibility that dysbiosis may be a feature of some cases of autism alongside a few other bits of speculation. Looking at these paper, I could imagine that some people would be put off by for example, the types of publishing journals used for these works, which almost seem to stress that dysbiosis is 'alternative' or 'complementary' and hence just for the 'tree-huggers'. It's not by the way - unless that is, you think Nature for example, is of a similar ilk (see here).
• Dysbiosis has been mentioned by a favourite researcher of mine, Harumi Jyonouchi (of SPAD fame) as part of this paper*** which was discussed in this post. The long and short of it was the potential for innate immune system issues in cases of autism to perhaps place someone at greater risk of things like dysbiosis. I was interested how this work might tie into quite a new piece of research looking at innate lymphoid cells (in mice) and how the immune system might act as a barricade to keeping gut bacteria from connecting with neighbouring tissues (see here). More work perhaps required on IL-22?
• Clinical findings suggestive of the presence of dysbiosis via analysis of organic acids have also been reported.  Another name mentioned in a previous post crops up, Dr Joanna Kałużna-Czaplińska, and her studies on urinary organic acids (here**** and here*****). Indeed, although not specifically mentioning dysbiosis in the title, the results published by Bill Shaw****** on the detection of 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) in the urine of a group of people with autism might also be relevant. I could also at this point mention the Yap/Nicholson paper and that recent speculative paper from Dr Clayton on bacteria and amino acids as part of the mix.

Obviously there are quite a few gaps in the research base with regards to autism and dysbiosis. The primary problem being that these and all the other studies which have been done on gut bacteria and autism are still very preliminary, based on relatively small participant numbers and really just 'fishing expeditions' in the absence of a reliable picture of what should or shouldn't be happening to gut bacteria in a more general sense.  As per the Williams paper, there is also the added interference from comorbidity to think about, noting the extent to which the HMP had to go to rule out some important variables like gum disease for example from complicating their results.

The next question is what can be done about dysbiosis if present? This is where I need to be careful and stick to my mantra about not giving medical advice or anything approximating medical advice. I have thought about this quite a bit and wondered if it is so easy as to just look at supplementing with probiotics or that other 'undesirable' therapy particularly where dysbiosis might be chronic rather than acute following use of antimicrobials for example. As a sidenote to that 'undesirable' therapy, I was interested to read a proper Doctor's take on this with autism in mind (here).

Going back to the Williams paper on carbs and autism, they (and their other paper) seemed to suggest that issues with the enzymes used to process carbs might be an initial starting point for dysbiosis. If this is true, the logical answer would be to either supplement with the relevant carb metabolising enzymes (or their cofactors if needed) or look at removing the foods which a person may have issues with metabolising. Whether or not this could tie into Dr Fallon's CM-AT preparation or even the usefulness of diets like the gluten- and casein-free intervention / GAPS diet is still source for investigation. I might add again that no advice or endorsement is intended.


I have a 'gut feeling' that gut bacteria and dysbiosis is going to crop up a lot more in autism research circles following the HMP publications and dare say this is not the last that you will hear from me on the topic. 


To finish, songs don't normally translate into images for me; aside that is from a dark, rainy Friday night at the guitar club described in the Sultans of Swing. "He can play the honky tonk like anything" apparently and as for the rain, it's a British summertime, what do we expect? 

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* Louis P. Does the human gut microbiota contribute to the etiology of autism spectrum disorders? Digestive Diseases & Sciences. June 2012.

** Williams B. et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS ONE. September 2011.
DOI: 10.1371/journal.pone.0024585

*** Jyonouchi H. et al. Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes. Journal of Neuroimmunology. 2011; 238: 73-80.

**** Kałużna-Czaplińska J. Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children. Clinical Biochemistry. 2011; 44: 686-691.

***** Kałużna-Czaplińska J. et al. B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children. Nutrition Research. 2011; 31: 497-502.

****** Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutritional Neuroscience. 2010; 13: 135-143.