I know that everyone (including me) wants answers to the question “how do you fix a broken biome.” I am always happy when I come across any information that may actually help people, especially since, at this point, there’s precious little known about how to actually make things better.
On Tuesday, I wrote about new papers on the adverse effects of excess levels of the short-chain fatty acid, propionic acid (PPA), on the developing brain.[i] At one point, in the paper on how PPA affects the amygdala (the emotion center of the brain), I was struck by the following sentence: “…recently it was established that the patients who are unable to metabolize PPA are more common than previously thought; many of such patients have cognitive impairments, movement disorders, and seizures.” The reference given was for a paper written by Dr. MacFabe back in 2013.[ii] I was curious – what did that sentence mean? So, I went and read that older paper.
Firstly, I have to say that it was a wonderful read – more “user friendly” than ordinary scientific papers. Dr. MacFabe talks about how he came up with the PPA theory of autism, and this story-like quality that makes it really enjoyable. To boot, there were some extraordinary bits of information in it that I absolutely need to share with you. In fact, there are so many that I’ll need to narrow things down to make sure this doesn’t turn into a Biome Buzz version of War and Peace.
1. To start, I learned a new term: “gap junctions.” These are defined as, “An organized collections of protein channels in cell membranes that allows ions and small molecules to pass between adjacent cells.”[iii] In other words, these junctions allow cells to communicate with each other.
2. Why is this important? Because it turns out that PPA closes gap junctions: “…closed glial gap junctions may render neuron hyperexcitable…In turn, this decrease in gap junction coupling may lead to inhibited cortical pruning in development, consistent with the larger brain sized found in ASD. Gap junction communication is involved in neurotransmission in the basal ganglia, prefrontal cortex, nucleus accumbens, and hippocampus: all areas that are implicated in seizure and movement disorders. Given these findings, it seemed possible that propionic acid-induced alterations to gap junction function and in neural development, as well as systemic effects (ie. GI motility), may play a role in ASD.” Thus, PPA has the potential to cause the pattern of brain issues seen in the autism population.
3. Back to the fact that difficulty metabolizing PPA is more common than once thought. There are apparently people with various inherited metabolic disorders, including one called propionic acid academia, who cannot metabolize this SCFA. There are much higher rates of these disorders than was recognized in the past. Dr. MacFabe references 2 papers from which he derived this information, one of which was published back in 2002: a study of 130,000 infants born in Japan found that, there was “…a frequency of patients with propionic academia more than ten times higher than reported.” There are mild forms of this illness which are much harder to detect. Why is this significant for the ASD population? Firstly, the overlap in symptoms between those with ASD and those with this inheritable disorder are remarkable: “…regressive cognitive impairment, seizure, and movement disorder, often in the context of GI symptoms.” Secondly, the difficulty of diagnosing PPA toxicity applies to both populations: “Propionic acid’s habit of ‘hiding’ inside cells makes it difficult to detect, even in patients with a metabolic crisis.” It does make you wonder if PPA toxicity in the autism population (or even in the non-autism population!) is not WAY under-diagnosed.
4. Back in May 2018, I wrote a post about Desulfovibrio bacteria in autism. In today’s paper, Dr. MacFabe mentions this and it’s worth bringing up here again to remind everyone that we are talking about a very complex dysbiosis: “Ongoing work by Dr. Finegold has identified further novel bacterial populations (ie. Desulfovibrio), which in addition to making propionic acid also produce hydrogen sulphide to damage mitochondrial function, thus potentiating propionic acid’s effects.” Science has barely scraped the surface of how these citizens of the human biome interact and affect each other.
5. We know that those on the autism spectrum have issues with mitochondria, the powerhouse of the cell. The cells are consistently “underpowered,” meaning that they work in a suboptimal way. As you can imagine, this has a major effect on the functioning of the body. PPA “…puts a ‘wrench’ in mitochondria…” by affecting the metabolism of carnitine, a substance that is critical in energy production in the mitochondria.
6. On the bright side (if there is a bright side in all this), there are some things that may help. Firstly, since PPA is produced in large part by certain members of the Clostridia family of bacteria, diets that reduce carbohydrate consumption may work as well as they do by reducing substrate for these bacteria. This may well explain the incredible efficacy of the Specific Carbohydrate Diet in autism.[iv] Giving carnitine and vitamin B12 to “…improve fatty acid metabolism or, in the future, eradicating/reducing ASD-associated propionic acid-producing GI-tract bacteria” may make a difference as well. (Don’t forget too, that back in September 2019, during the first Biome Buzz Propionic Acid Week, I described research showing that the old diabetes medication, pioglitazone (Actos), may treat the negative effects of excess PPA. I’m waiting for follow up studies on that.
I want to conclude with a wonderful sentiment expressed by Dr. MacFabe. In my personal opinion, the fact that he adheres to this belief is what makes him such an extraordinary researcher:
“The people who have taught me the most are the parents who refuse to believe what they were told – that their child’s regression and associated symptoms were all in their imagination….I must stress that we absolutely need the scientific rigor of asking the proper questions and designing the proper experiments and controls, but we also need the art of medicine and the ability to actually observe and listen to patients. The spark for understanding autism and the GI tract could come only from seeing the patients as an individual, not as a collection of symptoms, and seeing some of the assets as well as the disabilities in this condition. Deducing whether clinical expertise or science is more important in addressing enormous problems like ASD is like asking which half of a pair of scissors are more important. We need both.”
Truer words have never been spoken.
[i] Lobzhanidze, G, Lordkipanidze, T, Zhvania, M, Japaridze, N, MacFabe, DF, Pochkidze, N, Gasimov, E, Rzaev, F. Effect of propionic acid on the morphology of the amygdala in adolescent male rats and their behavior. Micron. 2019. doi: 10.1016/j.micron
[ii] MacFabe, D. Autism: Metabolism, Mitochondria, and the Microbiome. Global Advances in Health and Medicine. 2013;2(6):52-66.