Wednesday, 8 May 2013

Does melatonin affect leaky gut? Relevance to autism

Shocker alert: medicines might have more effects than those listed on the patient information leaflet.

I like being surprised. I particularly like being surprised about medicines and health, and how many of the medicines which even reside in the typical household medicines cabinet* might carry the potential to do so much more than that listed on the package insert.

 Leaking? @ Wikipedia  
Take for example the recent paper I bumped into by Sommansson and colleagues** continuing their scientific journey through the potential gastrointestinal effects of melatonin***. Melatonin - as many people with a connection to the autism spectrum disorders (ASD) or more generally neurodevelopmental disorders**** might know - is almost becoming the treatment of choice for issues with sleep disturbance*****. That's not to say it's for everyone, and also not necessarily the only potential option bearing in mind my caveat about not giving medical or any other advice.

I've talked about melatonin with autism in mind quite a few times on this blog (see here for example). Not only because the source material for melatonin (in the body) is tryptophan, one of those truly remarkable aromatic amino acids, but also because outside of the traditional sleep-wake link, melatonin might be quite the molecular 'handyman'****** (or handywoman). Indeed it is with the ethos of that last study by Boga and colleagues in mind that I head into the two Sommansson reports.

The first thing to note about the the Sommansson reports is that they are both studies on rats. I know that in recent times, there has been some chatter about using rodents to model conditions like autism (see here) focused in particular on the dangermouse that is the BTBR mouse model. In the current studies, the variable of rodent behaviour is not relevant given that the authors were looking at the physiological data pertaining to intestinal permeability (leaky gut) with melatonin as the primary variable.

Ah yes, intestinal permeability aka leaky gut. The same leaky gut that a recent NHS Choices entry described as being expounded by "largely nutritionists and practitioners of complementary and alternative medicine". Just for the record I am neither of those two occupational options but I am a believer in the concept in relation to quite a few conditions. And you can perhaps understand why I'm so interested in the Sommansson reports whereby leaky gut - or gut hyperpermeability - seems to be positively affected (i.e. reduced) by the introduction of melatonin, at least in rats. Indeed how this might fall into line with other observations of leaky gut being defined in cases of ASD (see here) and very possibly in a mouse model of autism (see here). A part of the effect of melatonin administration in cases of autism?

I'm not by the way falling hook, line and sinker for the author's observations that "melatonin reduces ethanol- and wine-induced increases in duodenal paracellular permeability partly via enteric neural pathways involving nicotinic receptors" being the same conditions as that found in cases of autism or any other condition. As far as I am aware children with autism are not knocking back copious amounts of alcohol, so one has to be careful about extrapolating such specific conclusions to the population with such tentative data. That and the fact that we currently know so little about gut barrier issues in cases of autism; assuming that people like this chap (yes, you Alessio Fasano with your zonulin et al) might shed some light on it in the near future. Oh and should I also mention the suggested link******* between melatonin being a modifier of toll-like receptor signalling too?

But... if anything the Sommansson papers might lead us to ask some pertinent questions about responses to melatonin both in general and also with autism in mind. A simple-ish experiment: two groups, randomised to melatonin or placebo, looking at the traditional responses to melatonin in terms of sleep and quality of sleep, at the same time some before and after measures of the lactulose:mannitol ratio and whether there is any correlation between supplementation, response and gut permeability. All fairly noninvasive by all accounts but if you really wanted to go to town you might also want to look at other measures like glutathione for example******** which has also found a spot in autism research.

But don't listen to my ramblings... listen instead to the these guys who are still going strong.


* Berk M. et al. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Medicine 2013; 11: 74.

** Sommansson A. et al. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo. Am J Physiol Gastrointest Liver Physiol. May 2013.

*** Sommansson A. et al. Melatonin decreases duodenal epithelial paracellular permeability via a nicotinic receptor-dependent pathway in rats in vivo. J Pineal Res. 2013; 54: 282-291.

**** Gringras P. et al. Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. BMJ. 2012; 345: e6664.

***** Malow BA. et al. A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics. 2012; 130: S106-S124.

****** Boga JA. et al. Beneficial actions of melatonin in the management of viral infections: a new use for this "molecular handyman"? Rev Med Virol. 2012; 22: 323-338.

******* Kang JW. et al. Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll-like receptor signaling pathway. J Pineal Res. 2011; 50: 403-411.

******** Swiderska-Kołacz G. et al. The effect of melatonin on glutathione and glutathione transferase and glutathione peroxidase activities in the mouse liver and kidney in vivo. Neuro Endocrinol Lett. 2006 ; 27: 365-368.

---------- Sommansson A, Wan Saudi WS, Nylander O, & Sjöblom M (2013). Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo. American journal of physiology. Gastrointestinal and liver physiology PMID: 23639810