Vitamin D and intestinal barrier integrity

I've learned some key lessons over the years when it comes to science and the interpretation of science. Probably the most important lesson is that rarely in science do you find a simple relationship between two variables. By this I mean that just because researchers report studying and finding a connection between one factor and one outcome does not necessarily mean it is that one factor which solely 'causes' or 'correlates' with that outcome. Indeed more often that not, several factors are connected to that outcome and the link is often pretty complex particularly when applied to the complexity of human (and animal) biochemistry.

I say all this because an interesting paper was passed to me a few weeks back authored by Kong and colleagues* (full-text) on the potential role of vitamin D and its receptors on the gastrointestinal (gut) barrier and in particular what happens to mice where vitamin receptor deficiency is present. There have been some interesting discussions on vitamin D in recent times. I note Emily Dean's post on vitamin D and depression as one. Keep this in mind for now.

With my autism research hat on, two primary concepts included in this paper were of immediate interest in that (i) 'issues' with the permeability of the gut barrier have been discussed for quite a few years with autism, some cases of autism, in mind and (ii) vitamin D deficiency has likewise been reported in some populations as a potential predisposing factor (think Sweden and Somali populations).

I admit that I am turning into quite a keen vitamin D research-watcher these days given the amount of research telling us that it does this and that. At the same time I am mindful that other vitamins/minerals/other compounds(?) have had a similar trendy following over previous years; thinking back to the age when vitamin C was the bees knees or more recently the tide that is omega-3 fish oils. We humans are a fickle bunch.

Anyhow back to Kong and colleagues. The paper is open access but once again the summary is as follows:

• Vitamin D receptor deficient mice were compared with wild positive mice when colitis was experimentally induced.
• Receptor deficient mice (homozygous for the deficiency) showed greater damage to the gut mucosa than those without the receptor mutation based on several different measures. The damage was pretty different between the two models and importantly, recovery of the mucosa following discontinuation of the induced colitis was less apparent in the deficient mice group than the control.
• Based on these results, the authors also reported on some experiments to assess why the damage occurred. So for example, they reported that treatment of various cells with vitamin D seemed to be linked to a stimulation of various tight junction proteins contributing to better mucosal integrity. They conclude that vitamin D deficiency might be linked to the increased incidence/prevalence of inflammatory bowel diseases (IBDs) in human populations based on this and other data.

OK perhaps I should have said that there were three potentially interesting links for this work back to autism with the additional suggestion that IBDs might also be involved (here).

Going back to how I started this post on one factor and one outcome, it is perhaps all too easy to overlay the findings back to autism and in particular, that potentially very important link with autism rates in immigrant populations in Sweden. As far as I am aware however there are a few important pieces of information missing from the current picture including (a) how many people with autism are actually deficient in vitamin D, (b) whether there are any problems with vitamin D receptors in cases of autism bearing in mind that receptor differences could be due to genetic issues or possibly infection, (c) whether Somali children/adults with autism show any difference in vitamin D levels or receptor activity compared with other ethnic groups with autism, and (d) is the incidence of gut hyperpermeability or IBDs any greater in Somali children/adults with autism over other groups with autism? Questions, questions, questions.

I might also add that gut hyperpermeability is a mighty complex thing which so far has not yet been studied in great detail with regards to autism. So alongside questions on what causes the hyperpermeability, there are issues concerned with what type of permeability is present (paracellular vs transcellular) and what about the expression of those all-important tight junction proteins with such lyrical names as zonula occludens 1 (ZO-1), the claudins and E-cadherin; all still requiring answers. It might also be useful to also know whether permeability if present, is limited to the gut or whether, as has been speculated by others, leaky gut might also translate into leaky other organs too (leaky kidneys perhaps?). The implications of the immune system meeting things like gut bacteria potentially as a result of leaky gut also need to be followed up.

I remain intrigued by the Kong findings on vitamin D and gut hyperpermeability in the mouse model and perhaps even more now, eagerly await the results of the promised studies looking in more detail at the risk of autism in Somali populations. Going back to the vitamin D-depression post, I do wonder how much this might overlap and whether another post by Dr Deans on depression and the leaky gut might, just might, figure in some shape or form.

To end a cover version of the Charlie Daniels Band classic by the Levellers. Fiddlers from Georgia at the ready...

* Kong J. et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 294: G208–G216, 2008.