I'm getting wary of studies on the gut microbiota. When they first started coming out the concepts and technology involved were all so new that each one was interesting.
Now they've become fashionable and everyone it seems is trying to get on the bandwagon. The result is a lot of pretty boring studies with not much new to say - they make some observations of differences in microbial composition in different circumstances, then wax eloquent about what this might mean in theory, rather than doing anything to find out what the differences mean in practice. I don't bother to read most of them anymore.
This one though is excellent.
They have gone to the next level and studied detailed mechanism by which gut microbes might be exerting some of their observed effects. Note though that the study is in mice. It would not have been possible to do most of the work in humans but now that details have been worked out it mice it will be necessary to determine if similar things occur in humans.
The study focussed on histones, proteins which package and order DNA and so play a role in gene regulation. An important way that histones themselves are controlled is through post-translational modification, the addition of small substances to specific amino acids (often lysine residues) in the finished protein which affect how the protein interacts with DNA.
You are probably familiar with methylation, the addition of a 1C unit, but there are several other types of modification. These authors looked at a newly described modification of lysine groups in histones called crotonylation. Crotonic acid is a 4C unsaturated aliphatic acid.
Please note that in the magazine article linked above, it is mistakenly claimed that crotonylation attaches an acetyl group. No, as the name implies, it attaches a crotonyl group.
Acetylation of histones, attachment of a 2C group, does also occur but is separate from crotonylation.
Perhaps the confusion arose from the name of the enzyme which removes crotonyl groups from histones - it is a member of the histone deacetylase family (HDA).
In general, crotonylation of histones tends to promote transcription of genes, in contrast to methylation which can both repress and stimulate.
In this study they first showed that crotonylation of histones is very common in the brain and the small intestine/colon. They didn't look further at the brain but in the small intestine/colon they found genome-wide crotonylation associated with transcription start sites.
In vitro and in vivo studies showed that SCFAs from bacteria, most notably butyrate, promoted crotonylation and the mechanism behind this is the inhibition by butyrate of the HDA enzymes which remove crotonylations.
They also went on to show that crotonylation is important in the cell cycle where addition and subtraction of crotonyl groups helps control the progression through cell division. This may be behind the apparently protective role of the microbiota and butyrate in particular against colon cancer, and presumably will be the subject of further studies.
