Wednesday, 17 October 2012

Leaky mice guts, bacteria and autism?

I might have said it before but I'll admit that I'm a fan of the work coming out of the laboratory of Prof. Paul Patterson. I've never really been one to take the whole hero-worship or anything like that too far (he says with history of toilet roll lightsaber duelling) but I'm certainly impressed with his work and often quite radical views in respect of conditions like autism and schizophrenia.

In a recent post on his blog, I (and a few others) were left decidedly tantalised by the promise of some future results appearing based on the continuation of his maternal immune activation impacting on offspring mouse studies. The fact that said results, presented at the recent Society for Neuroscience 2012 meeting, also linked into gut bacteria was an added incentive to keep an eye out for them.

Well, recently Virginia Hughes over at the SFARI blog posted an entry on the latest revelations titled: Probiotic curbs autism features in mouse model. I'm not going to re-hash the post here because everything you need to know is in that post, bearing in mind that these are conference proceedings and so are not yet peer-reviewed published results.

I will draw your attention to a few details however:

  • Aside from the behavioural presentation of maternally immune activated mouse offspring, there was a suggestion of "unusually permeable intestinal membranes". I know its still a little bit controversial to talk about leaky gut and autism, but suffice to say this is not the first time its been mentioned in the published research literature and not just in autism. Indeed, the whole bacterial translocation (bacteria ending up in places it really shouldn't) is also mentioned in passing albeit I don't think, part and parcel of the results yet.
  • "One such metabolite, 4-ethylphenylsulfate, shows a 40-fold increase in the blood of offspring born to infected mice compared with controls". I'm still searching for further data on 4-ethylphenylsulfate; but at the moment it seems this might be a uremic compound of some note.
  • Big quote coming up: Most provocatively, feeding young mice Bacteroides fragilis, a bacterial species that’s common in the healthy human gut, makes the intestinal barriers less permeable and normalizes levels of 4-ethylphenylsulfate in the blood. “[It] completely blocks leaky gut,” Patterson says. Wow. Completely blocks leaky gut? Makes me wonder how this might translate to compounds associated with leaky gut such as [General] zonulin

I tend to find there is a degree of standoffishness (is that a word?) when one mentions things like probiotics with autism in mind. Antibiotics and autism ... OK there's a history there too. Probiotics have however been mentioned in the peer-reviewed research domain with autism in mind as per the review from Critchfield and colleagues* (open-access) albeit with some way to go in terms of looking at efficacy and safety - and in the long-term too.

I'm not advocating anything on the basis of this conference report, a conference report on mice which certainly requires independent replication. What Prof. Patterson's research does however suggest is that even if in a subgroup of people diagnosed with autism, it is wise not to write off some involvement for gut bacteria just yet and a greater inspection of the immune-bacterial link related to cases of autism might be warranted.

[Update: 18/10/12: Similar findings to these will/were also presented at an in-house conference at CalTech (abstract here, bottom of page 2) scheduled for 20/10/12].

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* Crichfield JW. et al. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterology Research & Practice. 2011. 161358.