Biologists discover propionate supplementation as a potential treatment for Parkinson's disease (Via soluble fiber or supplementation or reducing B-12, strangely)

Medical Xpress / The University of Hong Kong / Cell Reports ^ | March 19, 2024 | Chenyin Wang et al

[ConservativeMind]

A research team recently discovered that propionate, a short-chain fatty acid (SCFA), strongly suppressed neurodegeneration in animal models of Parkinson's disease (PD) by regulating interorgan signaling between the intestine and brain.

Either inhibiting propionate breakdown or supplementing propionate through diet reversed PD-associated transcriptional aberration and enhanced energy production in the intestine, which in turn promoted neuronal health without the need of dispersing the protein aggregates.

PD is often characterized by the abnormal accumulation and aggregation of alpha-synuclein (alpha-syn) proteins in the dopaminergic neurons, which causes proteotoxic stress and neuronal death.

One class of bacterial metabolites that have attracted a lot of attention in recent years are the SCFAs (i.e., acetic acid, propionic acid, and butyric acid) produced by anaerobic bacteria through the fermentation of dietary fiber.

Using a C. elegans PD model, Professor Zheng's team previously conducted a genome-wide screen and identified 38 pro-neurodegenerative genes in E. coli. A few of these bacterial genes are essential for the biosynthesis of vitamin B12 which induces the breakdown of propionate in the host. Thus, the team hypothesized that increasing the levels of propionate may suppress neurodegeneration.

In this study, Professor Zheng's team found that PD animals have lower levels of propionate than normal animals and increasing the propionate level by either removing dietary vitamin B12 (which induces propionate breakdown) or through direct supplementation of propionate rescues alpha-syn-induced neuronal death and locomotion defects.

The low propionate abundance in turn caused the downregulation of numerous propionate-responsive genes involved in fatty acid and amino acid metabolisms and eventually leads to defects in energy production in the intestine, which further exacerbates neurodegeneration through the gut-brain communication involving lactate and neuropeptides.

Genetically enhancing the production of propionate in the intestine or restoring the intestinal expression of key metabolic regulators downstream of propionate significantly rescued neurodegeneration.

[ConservativeMind]

I was not aware that vitamin B-12 broke down propionate. If true, supplementing B-12 may be breaking down a beneficial item before we can use it.

Soluble fiber increases gut bacteria that make propionate we absorb through our intestines. You can also find propionate supplements, though.

[ConservativeMind]

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[Newbomb Turk]

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[ConservativeMind]

Do note it appears you can get too much propionate, too.

Propionate and Alzheimer’s Disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831739/

[RummyChick]

A more complicated issue would be how does the various genetic issues with breaking down B12 factor into this like the mthfr gene.

B12 genetic processing problems are not understood well by medical community. Neither are treatment plans. UK uses one kind of shot.US uses the one with cyanide in it.

You can have problems with b12 breakdown but still show a normal level of B12. Btw, metformin can cause B12 issues.

[GrannyAnn]

So true. I believe one B12 absorption issue is pernicious anemia. Most common amongst white Europeans and is related to the mthfr gene issue.

The body is so complicated, and we barely know the half of it.

[Cincinnatus.45-70]

Thanks.

[mad_as_he$$]

Thank you as always for posting this important study! I am passing it on to my friend that is cursed with PD.

[ckilmer]

I’m baffled by the multiple moving parts of this story. How would you suggest the simple and stupid address propitiate as a possible mitigator of neurodegenerative diseases? And KISS (keep it simple stupid)