Dr. Derrick MacFabe, Autism and The Metabolome

Many years ago, I first saw Dr. Derrick MacFabe speak at an autism conference.  It was among the most memorable talks I’ve ever seen.  Dr. MacFabe’s research centers around the cognitive and behavioral effects of bacterial metabolites (especially short chain fatty acids).

Propionic acid (PPA) is present in our diets, but more importantly, it is a byproduct of fermentation by autism-associated bacteria, including Clostridium. Clostridium is a family of bacteria that includes some good and some bad species.  For example, the bacteria that causes botulism is in the family of Clostridium. In fact, Clostridium is particularly associated with the gut bacteria that cause diarrhea during antibiotic use.  Many of you may have heard of recurrent Clostridia infections (C. difficile) occurring after antibiotic use:  this can actually be fatal.

While I knew, from my very first appointment for Alex with Dr. Sidney Baker, that there was this “gut-brain” connection in autism, it wasn’t until 2005 that I saw “proof” in the medical literature of these microbiotic differences, including excessive Clostrida: “Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.”[i] Dr. MacFabe’s first paper[ii] on the subject was written a year later.  He injected PPA directly into the ventricle of the heart (so into the blood stream) in rats to see what would happen and found that it induced, “…abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation….”

What really amazed me, watching his talk on this paper, was the video footage he presented of rats before and after exposure to the PPA.  This is something you won’t want to miss.  You can view these films starting around minute 33 of this video [iii]of one of Dr. MacFabe’s talks.  I mean, come on! – that rat who takes 3 steps and lies down, over and over!…absolutely wild!

According to Dr. M[iv], PPA can readily enter the blood stream from the gut.  In his rat models, in the short term, small amounts immediately produce hyperactivity, repetitive behaviors and social impairment.  The animals also, “…display brain electrical changes resembling some types of human epilepsy, which often co-exists with autism.”  Repeated administration of PPA over time, increases the severity and effects, which suggests “…that PPA can exert permanent effects on brain and behavior.”

The connection between autism and PPA from clostrium is not yet definitively proven.  However, this metabolomic idea – that byproducts of gut bacteria can directly affect the brain, behavior and development – is pretty well established.

Completely coincidentally: this morning, just before I got ready to post this, I came across the transcript of a Q&A with Dr. Kim Barrett, a professor of medicine at the University of California, San Diego, who is also the editor of The Journal of Physiology.  A summary[v] of that highlights one of the key points she made:

“… there are thousands of different species of bacteria in your gut microbiome, but Professor Barrett suggested the specific types of bacteria might be less important than the bacteria’s metabolic output — that is, the chemicals they excrete, and the effect those chemicals have on how your body works.”

How’s that for serendipity?!

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[i] Parracho, HMRT, Bingham, MO, Gibson, GR, McCartney, AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.  Journal of Medical Microbiology: 2005, 54, 987-991.

[ii] MACFABE, Derrick F.. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microbial Ecology in Health and Disease, [S.l.], v. 23, aug. 2012. ISSN 1651-2235. Available at: <http://www.microbecolhealthdis.net/index.php/mehd/article/view/19260>. Date accessed: 18 Jan. 2017. doi:http://dx.doi.org/10.3402/mehd.v23i0.19260.

[iii] http://media.archildrens.org/Mediasite/Play/a1f8898871354849aa03f7b0832b2f1a

[iv] http://www.psychology.uwo.ca/pdfs/autism/autismdigestion.pdf

[v] http://coach.nine.com.au/2017/01/19/11/25/gut-microbiome