Wednesday, 26 November 2014

The gut microbiome in Down Syndrome

The recent preliminary findings from Elena Biagi and colleagues [1] (open-access) reporting on the constitution of the gut microbiome - the collected bacteria which reside in the deepest, darkest recesses of our gastrointestinal (GI) tract - in a small number of cases of Down's syndrome caught my eye recently.
It's a funny feeling being taken
under the wing of a dragon

Perhaps a little bit unusually looking at the gut microbiome because of the link between premature ageing in Down's syndrome (DS) and "human aging... associated with a deterioration of the gut microbiota (GM)-host mutualism" researchers set about characterising the gut microbiota (GM) in 17 participants diagnosed with DS. Profiles from DS participants were "compared with the previously published GM profiles of 16 age-matching healthy adultsindeed previously published by some of the authors [2] which itself has been the topic of some discussion.

The results were not exactly spectacular insofar as: "DS persons and healthy adults showed comparable levels of GM diversity and an overall similarity in the composition of the GM community" again bearing in mind the small participant numbers. Indeed their hypothesis about premature ageing of the gut microbiota did not appear to be borne out by their small scale study.

That being said, one particular finding peaked my interest: "DS persons were enriched in Parasporobacterium and Sutterella, and reduced in Veillonellaceae." It is the Sutterella part and the comment: "The increase of Sutterella and the reduction of Veillonellaceae have been described in autistic children with gastrointestinal symptoms" which made me sit up. I've covered Sutterella a few times on this blog with autism in mind (see here and see here for some replication work). Whilst independent work has suggested that Sutterella (Sutterella wadsworthensis) might be nothing more than "a common commensal" [3] based on analyses of samples from "44 treatment naïve de-novo IBD patients and 42 with normal colons", I am still of the opinion that there may be more to see from this bacteria / bacterium.

The fact that Biagi et al also reported that "the abundance of Sutterella in the GM was positively correlated with the ABC [Aberrant Behavior Checklist] total score in DS persons, suggesting a possible link between this microorganism and ASD [autism spectrum disorder] in DS" is to my mind, worthy of some follow-up as a function of some growing links between DS and the autism spectrum (see here). Whether this extends to the recent suggestion of Down Syndrome Disintegrative Disorder [4] is also a question not yet answered.

Bearing in mind the recent revelation that at least some microbiome analyses might be suffering an XMRV moment as per the paper from Susannah Salter and colleagues [5] on reagent and laboratory contamination potentially affecting results (contaminomics as one commentator has put it), there does seem to be quite a bit more to do in this area with DS in mind. If one takes the collected microbiome work with autism in mind (see here also recently added to by the paper by Tomova et al) as a template, and where that might potentially lead in terms of interventions for example, applying similar logic to findings in relation to DS might offer some similarly intriguing opportunities to impact on quality of life.

Next up on the research menu to complete the gut triad: gut permeability and mucosal immunity in DS? What about gluten 'sensitivity' [7] and/or coeliac disease [8]? Too much?

Music, music, music.... Acceptable in the 80's? (shoulder pads etc.)

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[1] Biagi E. et al. Gut Microbiome in Down Syndrome. PLoS One. 2014 Nov 11;9(11):e112023.

[2] Schnorr SL. et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun. 2014 Apr 15;5:3654.

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

[4] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.

[5] Salter SJ. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biology 2014, 12:87

[6] Tomova A. et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiology & Behavior. 2014. November 6.

[7] Wolters VM. et al. Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability. Hum Immunol. 2010 Apr;71(4):392-6.

[8] Malt EA. et al. Health and disease in adults with Down syndrome. Tidsskr Nor Laegeforen. 2013 Feb 5;133(3):290-4.

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ResearchBlogging.org Biagi E, Candela M, Centanni M, Consolandi C, Rampelli S, Turroni S, Severgnini M, Peano C, Ghezzo A, Scurti M, Salvioli S, Franceschi C, & Brigidi P (2014). Gut Microbiome in Down Syndrome. PloS one, 9 (11) PMID: 25386941