A Metabolite Direct Link Between the Gut and the Brain: Think Autism, Parkinson’s, etc….

Today’s post describes what may be a critical finding in defining at least one mechanism whereby gut microbes directly affect the brain.  Those interested in developmental disorders, like autism; Parkinson’s; Alzheimer’s; chronic fatigue; etc. should pay particular attention as, according this article, this information is likely applicable to those illnesses, and many  more.

The relationship of neurological disorders to the gut bacteria is well established, as you know. This includes the developmental disorders and diseases mentioned above, as well as the development of anxiety, depression, etc. However, “…evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive.”  Thus, it’s a major step forward that scientists at the University of Glasgow have discovered two new molecules that are produced by gut bacteria and that can travel directly to the brain, crossing the blood-brain barrier.[i]  These molecules structurally greatly resemble carnitine, a compound derived from amino acids, which is critical in transporting fatty acids into the mitochondria of cells, where the fats are “burned” to produce energy.  In looking like carnitine, these molecules essentially take the place of the real compound, thereby preventing real carnitine from performing its essential functions, “…leading to inhibition of brain cell function.”

These 2 molecules appear to be made by certain members of the Clostridiales family (C. clostridioforme and C. symbiosum).  The authors of this paper theorize that these bacteria produce these “fake carnitine” molecules to give themselves a competitive advantage against species that do poorly in the presence of carnitine.  Not much is known about these two species, except that their presence “…in the gut microbiome is associated with low microbial diversity, while C. symbiosum presence could further distinguish obese from lean participants.”  We also know that these 2 strains are increased in the guts of those with autism, and completely absent in controls in studies comparing the two populations.

Mitochondrial dysfunction is well established in autism, as well as in Parkinson’s and Alzheimer’s.  In autism, carnitine has been looked at as a potential treatment for a subgroup of those on the spectrum.  A 2019 paper states, “Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency….Some people with autism (less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with L-carnitine is beneficial.”[ii]  Another 2019 review describes the few clinical trials yet done on the population, which, while small, also showed consistency in results:  there was improvement, often significant improvement, in the symptoms of autism.  (The doses and duration of treatment varied greatly in these trials, so the fact that there was general consensus as to the benefits of carnitine treatment, I’d think, make the results that much more significant.)[iii]

In digging around, I also found that some evidence of carnitine’s protective role in Parkinson’s, heart disease, type 2 diabetes, etc.  I also found studies linking low levels of carnitine with depression and anxiety.

Back to autism for one last thought:  as you know, from reading my many posts (two of many examples, here and here) on the work of Dr. Derrick MacFabe and others in the field, the short-chain fatty acid, propionate (PPA) is now generally accepted to play a significant role in the development of many cases of autism.  Abnormal gut bacteria, which includes high levels of clostridia (PPA producers, as well as the producers of these carnitine-like molecules), in the population – possibly combined with food sources (PPA is a common preservative) are likely to blame.  High levels of PPA cause a reduction in carnitine levels:  “PPA is thought to affect mitochondrial fatty acid metabolism by sequestering carnitine.”[iv]  So now we are faced, thanks to this altered gut microbiota, with both a reduction of carnitine levels and these carnitine-analogs which replace what little carnitine is available, further destroying normal mitochondrial function.  This, in turn, affects the way energy is produced in the cell and thus, the way the brain develops and functions.

Animal (dairy, meat, fish) products contain carnitine.  If you tend to avoid these in your diet, and are among the susceptible population, you may want to consider supplementation. (Of course, talk to your health care practitioner first.) Carnitine (best taken in the form acetyl-l-carnitine) is a very low risk supplement.  Only in high doses, 3000 mg per day or more, can it have side effects including nausea and vomiting. Strikes me that this may be another can’t-hurt-could-help kind of thing.

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[i] Heather Hulme et al. Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication, Science Advances (2020). DOI: 10.1126/sciadv.aax6328

[ii] Demarquoy, C and Demarquoy, J. Autism and Carnitine: A possible link.  World Journal of Biological Chemistry. 2019;10(1):7-16.  doi: 10.4331/wjbc.v10.i1.7

[iii] Malaguarnera, M, and Cauli, O. Effects of l-carnitine in patients with autism spectrum disorders: review of clinical studies. Molecules. 2019;24(23):4262.  10.3390/molecules24234262

[iv] Thomas, RH, Foley, KA, Mepham, JR, Tichenoff, LR, Possmayer, F, MacFabe, DF. Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. Journal of Neurochemistry. 2010;113:515-529.  oi: 10.1111/j.1471-4159.2010.06614.x

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