Day two – Francisco Guarner on Ulcerative Colitis

Now heres a talk close to home.

There are 47 suceptibility genes, of which 28 loci are shared between crohns and UC. Candidate genes are responsible for innate . However genetics isn’t the story. Carrying the highest risk SNP has only a 1.7% chance of giving you UC. Enviromental conditions are much more important. The prevelance of UC varies greatly by location. So whats going on?

The immune system does not properly tolerate communusal gut bact. There is a much greater expression of TNFa in crohns, which the most effective modern treatment, remicade, lowers. In the inflamed tissue of crohns the presence of non pathogenic bacteria increase TNFa and immune responses like IL-17, t-lymphoycotes and decreases the amount of cells undergoing apoptosis. It’s not the bacteria, because immune suppresents work to cure the disease. The problem is TNFa. the tissue is destroying itself by reacting agaisnt communsal bacteria.

Maybe the bacteria in the enviroment has cahnged, maybe they react in a different way.

The microbiome of people with IBD is not normal. We have less diversity of genes than non IBD controls. 12 metaspecies were associated to UC, 7 lower and 5 higher in UC. This was controled by healthy first degree relatives. Using a statistical test only 4 metaspecies showed good discrimiatory capacity between UC and health.

So bacterial sepcies are correlated with IBD, but are they causative?

Faecal Mucin was studied to see if there would be a diff in colonization between remission and active but there wasn’t. However the normal colonisers had been lost. UC is correlated to a loss of the bact. Akkermansia

Probiotic temporal instability may be a consequence of low biodiversity, enriching the ecosytem could stabilize. Many probiotics are anti inflammatory. They did a study on this but have not finished their analysis yet

I have a lot to say about this but we’re moving on to the next speaker. This is way fucking different than how crohns had been explained to me before just a few years ago, and no explanation ever  fit to the data. Way to drop the ball modern medicine, but thankfully they are getting closer to a better understanding.

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