Short chain fatty acids and ammonia in autism

It is perhaps apt that Jon Brock over at Cracking the Enigma recently posted about the Australasian Society for Autism Research highlighting the various links being forged regarding autism research in that part of the world. Apt because there are several very good autism research groups producing findings which have some potential real-world application to autism, in that part of the World. I speak in particular of the team based at the Sansom Institute for Health Research based at the University of South Australia. Members of UNISA recently publishing a fine review of how glutathione and relations show quite a consistent relationship to cases of autism. Autism research movers and shakers please take note.

Indeed another paper published by Wang and colleagues* adds to the repertoire, suggesting that levels of fecal short chain fatty acids (SCFAs) and ammonia were higher in their cohort of children with autism compared to asymptomatic controls and hence showing alteration in the fermentation process.

As a sort of introduction to SCFAs and fermentation, readers might find this article by Topping & Clifton** (full-text) and this article by Macfarlane & Macfarlane*** (full-text) to be of interest. Basically, think carbohydrates and gut bacteria and eventually you head the direction of SCFAs. If you happen to brew your own beer, fermentation might not necessarily be a strange concept alongside memories of 'auto-brewery syndrome' (not personal memories I might add).

Unfortunately I can't post a link to the full-text but here are a few details:

• Based on the collective studies of Dr Wang's PhD (scroll down to see her thesis details), this study looked at fecal specimens from a relatively small group: 23 children (mean age ~ 10 years) diagnosed with ASD compared with 31 age-matched controls.
• Although not everyone's choice of biological medium to work with, fecal samples - as in poo samples - were analysed via various methods including colorimetry (ammonia) and gas chromatography (SCFAs). Other compounds such as p-cresol were analysed via liquid chromatography.
• Results: fecal concentrations of total SCFAs were elevated in autism samples (p=0.012) as were levels of ammonia (p=0.007). Interestingly no elevation was observed in levels of p-cresol in autism samples as has previously been described. 
• More specifically with individual SCFAs, some interesting compounds cropped up as being elevated in autism samples including: propionic acid, butyric and isobutyric acids and valeric and isovaleric acids. Indeed out of the battery of SCFAs analysed, only caproic acid showed no significant difference between the groups.
• The authors conclude that fecal levels of these large bowel fermentation products might tie into the accompanying gastrointestinal (GI) findings observed in some children with autism and differences in the bacteria inhabiting the darkest recesses.

There are some obvious caveats to accompany this latest study. Aside from participant numbers being relatively small and covering quite a lot of chronological age in childhood, and the slight discrepancy in controlling for gender, there was quite a bit of 'overlap' when it came to individual results from the autism and control groups. Indeed if I were to criticise at all, I perhaps would have like to have seen some plotted information on the dispersion of values obtained from individuals just to visualise and ensure that results were not skewed by a few outlier results. As has however been discussed recently, outliers in a heterogeneous condition like autism are very often a source of great interest.

This is not the first time that the words 'autism' and 'fermentation' have come to my attention. Quite a few years back I remember some interesting work being done at Cranfield University by Maria Pilar Bilbao Montoya as part of her higher studies. Working with gastroenterologist, John Hunter, Maria presented some initial work suggesting similar things in their cohort I believe. I might be wrong but I also remember that Dr Sophie Rosseneu might have had some unpublished work in this area also as a tie up with her findings on yeasts and autism?

Memories aside, there are some interesting points to take from this research. SCFAs such as propionic acid (PA) have recently been seen in the autism research arena as per this paper (full-text) by El-Ansary and colleagues looking at what happens when you inject rats with PA in sizeable quantities. For those of you who are unimpressed with the proposed PA-gut-brain link, maybe a few other choice papers might be useful, here and here. And perhaps some evidence for the presence of PA in other biological fluids from cases of autism?

I've talked ammonia before on this blog with reference to some mitochondrial findings. Wang and colleagues look more to the GI effects of ammonia given that it was detected in stool samples and how this might tie into issues with gut permeability so commonly discussed. Indeed ammonia - the whole nitrogen balance - takes us back to some old friends, glutamine and glutamate, one of which has been making quite a bit of news lately (here's the paper abstract).

The big question has to be why the reported differences in this latest study? I can't give a specific answer to this question but given the interest in carbohydrate metabolism and autism, the suggestion of things like lactose intolerance, added to the growing research base on gut bacteria and autism, one has to suspect that the answer might lie, partially at least, somewhere in these regions.

* Wang L. et al. Elevated fecal short chain fatty acids and ammonia concentrations in children with autism spectrum disorder. Digestive Diseases and Sciences. April 2012
DOI: 10.1007/s10620-01202167-7

** Topping DL. & Clifton PM. Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides. Physiological Reviews. 2001; 81: 1031-1064

*** Macfarlane S. & Macfarlane GT. Regulation of short chain fatty acid production. Proceedings of the Nutrition Society. 2003; 62: 67-72