Wednesday, 21 October 2015

Another mouthful

There is a huge, complex and infinitely fascinating ecosystem real close to my heart: about 15cm South in the transverse loop of my colon. Of course, it's only 'huge' in the fractal sense: it's much smaller that the Serengeti but it now has almost as many named species. Remember Bacteroides thetaiotaomicron ? It has a curiously long name whose origins I've still not been able to explain and it does useful things in our guts. Up until last night, I hadn't even heard of another polysyllabic microbe Faecalibacterium prausnitzii, let alone hazarded spelling it correctly. In contrast to B.θιο, there is no mystery in the name. It is the only species in its "Poo-bugs" genus and the specific name honours the late great German microbiologist Otto Prausnitz. DNA evidence wrenched it from the genus Fusobacterium 20 years ago. That was a very strange place to put F. prausnitzii because it is more closely related to Gram-positives like Clostridium than the Gram-negative Fusobacterium. There is also increasingly less mystery about its function which is important because it makes up between 5%-15% of the gut flora in healthy adult humans. For a single species out of the 1000-10000 bacterial types 'down there' that makes it a big player probably the most numerous.

Normally, your intestine, and mine, is in balance. It's not a monoculture of E.coli or F.prausnitzii or anything else. Harry Sokol and Philippe Langella in Jouy-en-Josas, France are working on the interface between gut microbes and host health and happiness. One of their key findings is that F.prausnitzii is conspicuous by its absence in people with inflammatory bowel disease IBD. IBD manifests in a suite of uncomfortable symptoms and is given different names depending on how flarey-uppy, how bloody and how persistent these symptoms are: ulcerative colitis UC, irritable bowel syndrome IBS, Crohn's Disease CD. The absence appears to be because F.prausnitzii is extremely oxygen sensitive EOS.  One of the effects of an inflammatory response is to send in a bunch of white blood cells that release reactive oxygen species ROS to clean up the threat. This takes out at least for a while. But one of the biochemical capabilities of is the produce lots of butyrate by partial oxidation of glucose. Butyrate has been shown to reduce the severity of inflammation in colitis when, for example, added to the darkness intra-rectally. Because of its extreme sensitivity to oxygen, it is difficult to grow on a petri dish in the lab. Clostridium difficile C.diff , a relative, is also, like Eleftheria terrae, notoriously difficult to culture. But progress has been made in working out a cocktail of additives [flavins and cysteine or glutathione] that will allow laboratory culture. That's good because you can then imagine scaling up to produce a generous handful of that can be introduced to suppress IBD.  This approach has shown considerable success against C.diff, which is a single rogue species that gets the upper hand in peculiar and particular circumstances - like in hospital after a heavy dose of anti-biotics.  With IBD it's not so easy because IBD is a wholesale shift in the make-up of the microbiota.

Think Serengeti.  Even after 60 years of studying the East African ecosystem, we have a very superficial understanding of the interactions. Literally superficial because we haven't a bog's notion about the role of the soil microbiota.  If one species of antelope or monkey gets uppity the managers of the wild-life reserve could perhaps deal with it: rifle, virus, predator. Although many such rough, simplistic human 'remedies' create as many problems as they solve - like cane toads Bufo marinus Rhinella marina in Australia. If it rains for 60 days straight and the Ngorongoro crater next door to Serengeti fills up with water and half the inhabitants drown then a quick-fix is less conceivable.
I started off down this rabbit hole after reading a 26th Feb 2015v Nature Supplement: Innovations in the Microbiome.  It's all behind a goll-darned paywall, though!  Harry Sokol seems to be on ResearchGate, I'll have to work out how to 'upvote' or 'like' or 'thumbs-up' his work and resist the temptation to endorse-bomb the poor fellow.

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