Friday, 8 November 2013

Sutterella and autism: replicated

Whilst quite a lot of attention is currently being paid to the study by Warren Jones and Ami Klin* on 'Autism signs being present in first months of life' I'm heading off in a slightly different direction in this post. It's not that I don't find the possibility that the eyes may be more than just the windows to the soul, or at least "a decline in gazing at eyes [might] accurately predict the development of autism" an exciting prospect, it's just that I'm waiting for some more confirmatory evidence before getting too enthusiastic about this. Replication, as you'll see later in this post, is an important part of autism research these days and the autisms are a very heterogeneous set of conditions.

Bowel not bowl... @ Wikipedia 
My post a while back on the paper by Brent Williams and colleagues** (open-access) regarding the detection of gut bacteria belonging to the genus Sutterella in cases of autism (see here) continues to be one of the most read entries on this blog. It follows a trend that seems to be apparent on this site: readers seem to be very interested in bowels and stools and bacteria all in the name of autism research and science. Or maybe it's just me being a little too obsessed with writing about them?

No mind. I personally found the Williams findings to be absolutely fascinating. Not only because of the fact that they report that "Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI)" but also the implications of their finding of "plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children" which also brings the concept of gut hyperpermeability squarely into the frame (see here). The authorship group also held significant prowess.

Bearing in mind the variable research base on a possible role for gut bacteria in cases of autism (see this post and this post) reflective of this being an emerging area for autism research, I'd like to think that the paper by Lynn Wang and colleagues*** (open-access) is another important addition to the collected text. If anything, their findings that "numbers of Sutterella spp. are elevated in feces of ASD children relative to controls" are a useful part of the scientific issue of replication, which we've been hearing something about with autism research in mind in recent times (see here).

The short report from Wang et al details findings based on the examination of fecal samples from a small group of children diagnosed with an autism spectrum disorder (ASD) compared with sibling and typically developing controls. There is an obvious difference between this paper and the one by Williams and colleagues around the tissue type used to assay for bacterial content; Williams relied on biopsy samples taken from various sections of the gastrointestinal (GI) tract. That being said, this difference is not necessarily a bad thing as per the assertion by Wang that "fecal samples may suffice for the detection and quantification of Sutterella in the human gut, including children with ASD". Biopsy = invasive, poo sample = not invasive (or at least not as invasive in terms of collection, but just make sure you wash your hands afterwards).

I was also interested to read about the very preliminary observation when comparing those children with GI issues - caregiver reported GI issues - and another type of bacteria called Ruminococcus torques. Another quote from the paper I'm afraid: "Significantly elevated absolute numbers of R. torques were evident in children with ASD whose caregivers reported them having a FGID (nine individuals) compared to those without reported FGID (14 individuals)".

FGID by the way, means functional GI disorder à la things like constipation and diarrhoea (see here); conditions which have very recently been confirmed as associated with autism**** yet again (see here for some commentary). Yes, it was only a very small number of participants and yes, it was based on bowel habit data solely derived from parental report. But don't underestimate the power of the parental report when it comes to such toileting issues with autism in mind (see here). Interestingly, this is also not the first time that R. torques has been mentioned with autism in mind as per the study from Sid Finegold and colleagues***** (open-access) a few years back.

I had heard that this new Sutterella paper would be arriving to the peer-reviewed table as far back as May this year (2013) as per a poster delivered at IMFAR (see here). Indeed Dr Wang's publications as part of a very active research consortium including Dr Manya Angley and colleagues at the University of South Australia are a favourite on this blog as per mention of things like Akkermansia muciniphila and autism (see here) which has also gone on to other things (see here). Indeed I was honoured to be able to read Lynn's very comprehensive PhD thesis which, I have to say, certainly put my efforts a few years back to shame.

Questions still remain about this issue of Sutterella and autism outside of just being identified as being present more frequently in cases of autism. How does it become predominant for example? And as per the chatter about baby immune systems and the process of bacterial colonisation, is early infancy the key or are we talking later on in development? I note also that the initial talk about Sutterella being linked to conditions like inflammatory bowel disease (IBD) has subsided following further exploration of any relationship****** (open-access) so the question of what role or association it might play is still up for grabs.

Indeed, I don't think either we're currently, definitively, able for example, to say that such bacteria (and potentially others) can actually influence the overt presentation of autism as per the psychobacteriomics paper recently reported. That being said, I think back to the gut decontamination study of Sandler and colleagues talked about in this post and their use of the potent antibiotic vancomycin as possibly presenting some new avenues of research exploration. As I've said a few times on this blog, the triad of immune function, gut barrier integrity and gut bacteria might eventually turn out to be important for some cases of autism (as they seem to be in other areas of research), but the relationship between these elements and onwards to the presentation of more commonly described symptoms is still quite a bit of a mystery.

Still, replication is replication. And with the Sutterella story, scientific replication with gut issues in relation to some of the autisms in mind is moving along rather nicely.

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* Jones W. & Klin A. Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism. Nature. November 2013.

** Williams BL. 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. 2012 Jan 10;3(1).

*** Wang L. et al. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Molecular Autism. 2013; 4:42.

**** Chaidez V. et al. Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development. J Autism Dev Disorder. November 2013.

***** Finegold S. et al. Gastrointestinal Microflora Studies in Late-Onset Autism. Clin Infect Dis. 2002; 35 (Supplement 1): S6-S16.

****** Hansen R. et al. The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study. PLoS One. 2013;8(3):e58825.

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ResearchBlogging.org Lv Wang, Claus T Christophersen, Michael J Sorich, Jacobus P Gerber, Manya T Angley, Michael A Conlon (2013). Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder Molecular Autism DOI: 10.1186/2040-2392-4-42