Tuesday, 10 January 2012

Autism and Sutterella

Barely a few days into 2012 and like the tulips in my garden sprouting very early this year because of our exceptionally mild winter, the first research papers of the new year are popping up through the scientific soil. Two studies have so far caught my eye: the first by Harumi Jyonouchi and colleagues* (full-text) looked at some potential overlap between cases of autism spectrum condition and specific polysaccharide antibody deficiency (SPAD); the second by Brent Williams and colleagues** (full-text) reported on some of the differences in gastrointestinal (GI) bacteria present in children with autism compared with controls.

I am going to leave the Jyonouchi paper for now, except for pointing out quite an interesting detail from the paper suggesting that levels of the anti-inflammatory cytokine IL-10 seemed to be an issue (lower) for many participants with autism compared with asymptomatic controls. IL-10 has cropped up before in autism research circles and might yet hold some interesting clues about things like inflammation.

The last paper that I discussed on this blog from Brent Williams holds a special place for me in terms of it uniting gut bacteria, carbohydrate metabolism and GI issues in some cases of autism. His latest offering was therefore always going to be one to watch for me. Before progressing with the summary, it is interesting to note the involvement of Prof. Ian Lipkin in this research. I have quite a bit of time for Prof. Lipkin and his pretty extensive repertoire of research that he has published on ranging from maternal infection inducing subtle neuropathology in offspring to the continuing saga of viral infections 'associated' (?) with conditions like CFS/ME. This is a chap who is not afraid of a little controversy.

The paper is open-access but just in case:

  • Biposy samples from 23 participants diagnosed with autism and gastrointestinal (GI) symptoms were compared with 9 samples from control participants with GI symptoms. Ages ranged from 3-10 years old.
  • Same as last time, pinch biopsies were taken from the terminal ileum and cecum. Various methods were used to analyse these samples including a novel PCR method used to detect and quantify bacteria from the Sutterella genus.
  • Following on from the previous findings of a high abundance of sequences from the Alcaligenaceae family in quite a few of the samples from the autistic group, further more detailed analysis showed that "all sequences of Alcaligenaceae found in AUT-GI patients’ biopsy samples were classified as members of the genus Sutterella". Sutterella presence was confirmed by their super-duper PCR method and the presence of various strains of Sutterella are reported for individual participants. Wikipedia has a more in-depth discussion about categorising bacteria on the basis of their taxonomic rank.
  • Plasma antibodies against a specific strain of Sutterella (Sutterella wadsworthensis) were also detected in the autistic group (IgG) (IgM antibodies in one case) confirming its presence. 
  • In total 12/23 (52%) of the autism group were PCR positive for Sutterella compared with none of the control group. This is the point that most of the media so far have focused on.

Sutterella, apparently named in memory of one Vera Sutter, who as the linked article suggests worked with Sydney Finegold (remember this paper) is a bacteria that I've not come across before. This paper describing the discovery of S.wadsworthensis explains it as a gram-negative bacteria thriving in low oxygen or anaerobic conditions. Sutterella has been previously linked to inflammatory bowel disease such as Crohn's disease although the more recent data has cast some doubt on the exclusivity of this link.

Whilst the methods and findings used in the current study are interesting, I wait to see where this work will go. It is interesting that in the discussion, the authors talk about abnormal intestinal permeability (the so-called leaky gut) and the potential resulting consequences of the the immune system meeting GI bacteria in places where they shouldn't really be meeting. In this study they specifically looked at plasma antibodies against S.wadsworthensis. The question is: what other antibodies might be present in cases of autism against other GI bacterial companions and what the net effect of this antibody load might be on a person. Interesting that increased epithelial IgG density has been noted before in cases of autism and bowel enteropathy.

I remain very attentive to this whole area of gut bacteria and autism (and other conditions) and hope to see a few more papers like this one in 2012 further probing the various goings-on of our bacterial masters. To finish, a song about a different type of bloom.

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* Jyonouchi H. et al. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): Case study. Journal of Neuroinflammation. January 2012.

** Williams B. et al. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. mBio. January 2012

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ResearchBlogging.org Williams BL, Hornig M, Parekh T, & Lipkin WI (2012). Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. mBio, 3 (1) PMID: 22233678

16 comments:

  1. Fascinating and for our family a possible understanding of recent events. My 20 yr old nephew who had been having pain associated with ulcers that appeared to be healing became increasingly distraught over the continual pain and on Dec 26th of this year took his own life. My sister who is a RN sent me this article and we find ourselves wondering if this could have been the missing puzzle piece that no one identified after numerous scopes, scans, and labs. I am curious if these findings would also mean that a milder form of autism, specifically aspergers (which we felt he had but was never diagnosed with) would also be associated with the sutterella bacteria. If so, it's astounding to think that a correct treatment for GI problems was dependent on a correct diagnosis for a developmental disorder. Thank you so much for your blog.
    Ellen Wilson

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  2. Many thanks Ellen and welcome. It is always a tragedy when the events you talk about occur particularly in one so young.
    As far as I am aware, this is the first time Sutterella has been linked to autism spectrum conditions and so at the moment we are limited to these findings and await further study. For the most part this paper was more about the various ways and means of finding and confirming the presence of Sutterella following on from the same teams' last paper which linked gut bacteria, issues with carbohydrate metabolism and GI issues in some cases of autism. There is still some speculation as to whether Sutterella is anything more than just a harmless bystander or something rather more pathogenic as per the Georgina Hold study on IBD and Sutterella: http://aura.abdn.ac.uk/bitstream/2164/2168/1/A_Comprehensive_Evaluation_of_Colonic_Mucosal_Isolates_of_Sutterella_wadsworthensis_from_Inflammatory_Bowel_Disease.pdf
    Having said that this does not rule out a more generalised role for this and other type of bacteria in cases of autism, and indeed highlights other issues such as the gut hyperpermeability issue as having the potential to turn something harmless into some rather more problematic.

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  3. Are these patients Sutterella + treated with antibiotics ?

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  4. Hi Didier. From what I remember there is nothing in the paper mentioning treatment with antibiotics in this cohort. These are children with autism also presenting with gastrointestinal issues. Whether there is other information, I don't know.

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  5. these latest findings are really making me remember an event. about 2 years ago our 5 year old son (pretty severe asd) had to go to the ER and they treated him there with a high IV dose of rosefin (sp?) for non asd related infection. But, for the next several days to a week his behavoirs and cognitive function were very noticibly better. other times, he has had a few other anitibiotics orally without any noticibale change. but we have always been wondering what that great response was about. maybe this is a clue ?

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  6. Interesting story. Noting that I am not giving medical advice, from what I read, ceftriaxon (Rocephin) has quite a lot of activity and uses. I'd like to think that subsequent research on Sutterella and the various other bacterial species linked to cases of autism might start looking at how susceptible such bacteria are to the range of antimicrobials available (bearing in mind that antibiotics and the fear of resistance need to be used with great caution).

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  7. Fascinating!!! My 13 yr old son, Jordan, is Asperger's and was recently hospitalized with Acute Rhuematic Fever with follow up treatment of Penicillin for the rest of his life. With that we began giving him a heavier dose of pro-biotics along with some natural anti-inflammatories, Protandim and Zyflamed to counteract the destruction of good flora from the anti-biotics. Jordan has always had intenstianl issues along with gas and processing any form of carbohydrates. We have found since taking the probiotics and anti-inflammatories that his stomach and intenstinal symptoms have decreased. Any thoughts on that? And how would I have him tested for Sutterella?

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  8. Hello Sweet Surrender and welcome.

    Thanks for the comment about your son which is very interesting indeed.

    Unfortunately I am not a medical doctor so am unable to provide specific advice. What I will say is that there is some [preliminary] evidence about the use of probiotics in certain bowel-related conditions such as IBS. Here is a link to a review of some of that research: http://www.ncbi.nlm.nih.gov/pubmed/21992954

    As for the carbohydrate metabolism issues, it has been raised before in autism (on more than one occasion) - http://questioning-answers.blogspot.com/2011/03/enzyme-activity-milk-and-autism.html & http://questioning-answers.blogspot.com/2011/09/carbs-and-dysbiosis-in-autism-reloaded.html

    At the moment I can't point you in any specific direction for Sutterella testing aside from perhaps suggesting that you contact the authors of the study for their view on this.

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  9. Hi, I have had cfs for about 25+ yrs, mlong term anitibiotics for rhematic fever as a child, as a child then parasite for 15 yrs in my early 20's and again massive antibiotics for that and other infections. For the past 12 yrs I have managed my health by not eating carbs, whenever I ate any carbs I got brain fog, cognitive, memory, emotional problems, fatigue, and the weight just piled on and wasn't in proportion to what I had eaten. Last year I underwent donor stool infusion at the Centre for Digestive Diseases in Sydney in order to correct altered gut flora. Prior to that I took the antibiotic Rifampicin and biofilm enzymes as per Dr Usmans biofilm treatment. That turned my life around, the weight just fell off me all my symptoms disappeared and my health returned to what it was in my teens and my cognitive ability improved markedly - I was a new woman, a woman I had never known, my life was fantastic for the first time I was the true me. I can't describe how wonderful a feeling of health I had. However after several months following the stool infusion and eating carbs for the first time in over a decade with no problems my symptoms started to creep back in and the weight/fluid retention started to increase again. Now I again have no carbs to manage my health. I have also been taught how to do home donor stool infusion as I just can't get the good flora to take up residence in my bowel. I know there is inflamation in my gut lining and I am convinced there is an infection residing there. This new discovery of Sutterella has given me confidence that I am on the right path to solve my illness. I have lost so many years of my life to this illness and I think this is at the base of it. Denise

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  10. Thanks for comment Denise.

    A very interesting history. The more recent research around bacterial transplantation is starting to look very promising for quite a few conditions: http://gutness-gracious-me.blogspot.com/2011/10/bacterial-transplantation-undesirable.html

    Dr Borody (who I assume you were seeing) is making some interesting progress in this area and at last some of his ideas are starting to take a foothold in more mainstream circles.

    At the moment, the Sutterella findings are quite specific to autism (or least this cohort of children with autism ). I would however imagine that more people will become interested in the findings and perhaps start looking at other conditions such as ME/CFS with this and other bacterial species in mind.

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  11. Maybe this is also why children with autism seem more cognitively aware when they spike a super high fever. My daughter has the most eloquent speech when she is febrile above 101 for a day.

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  12. Thanks for the comment Rendi.

    Fevers and autism has been discussed on a related post, in light of some interesting data which may mirror your experiences:

    http://pediatrics.aappublications.org/content/120/6/e1386.long

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  13. Hello Paul,

    I am a follower of your blog and I respect very much the neutral way you analyze the diversity of scientific articles. I would love to hear your opinion on the "Discovery of Abnormal Gene Pathways Suggests Targets for Future Medicines" and how this discovery fits the gut brain theory (in which I belive). Thank you.

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  14. Many thanks for the comment Monica.

    I think this refers to the work of Eric Courchesne and this paper (full-text):
    http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002592

    It built on a previous study which I discussed a few months back:
    http://questioning-answers.blogspot.co.uk/2011/11/brains-epigenetics-and-neuron-numbers.html

    I will need to have a good look at the paper and see what the conclusions are. It is always interesting to see these 'system biology' papers comes out and the myriad of information they produce bearing in mind that CNVs / mutations / SNPs may not necessarily be the whole story as per the rise and rise of epigenetics (changes to gene function not due to changes to genes). I would also perhaps caution on the participant group used and as I understand it, how they passed away (some on Twitter indicated that a proportion of participants died following complications related to epilepsy; the question then is what exactly are we looking at: autism or epilepsy or both?)

    As to the gut-brain theory, well genes related to immune response and inflammation featured quite heavily in the findings and I note a few mentions of the words 'auto-antibodies' which are perhaps also important issues. With my opioid peptide hat on, I do wonder if some of these genes may well eventually relate back to the 'pruning' effects of some of our endogenous peptides as per some forgotten research:
    http://www.ncbi.nlm.nih.gov/pubmed/2029640

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  15. hey there paul, I am very interested autism research. In my literature searches I can only find papers that associate guy microbiota alterations in individuals who happen to have autism. But I am having a hard time finding papers that deduce a causative relationship between the microbiota differences and ASD. Has there been a paper published like this that you know of?

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  16. Many thanks for the comment cnxangel.

    'Causation'... mmm, now there's a challenge. I'm afraid that I can't point to anything at the moment suggesting that gut bacteria 'cause' autism in much the same way that there is only scant peer-reviewed evidence of anything causing autism outside of some interesting case studies and other judgements. It's most likely a more tangled picture than just one factor being causative and with a high degree of certainly nothing universal for autism or anything else.

    I will think further about this and maybe make a short post if anything crops up.

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