Gut: The role of microbial amyloid in neurodegeneration.

[aspergerian]

New term for role of microbiota in neurodegeneration proposed.

sciencedaily.com/releases/2...

PLOS Pathogens, 2017; 13 (12): e1006654.

journals.plos.org/plospatho...

[exciting!]

[BUZZ1397]

That is hopeful

[park_bear]

The most interesting reference was this one: "Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD"

cell.com/cell/fulltext/S009...

[jeffreyn in reply to park_bear]

Hi park_bear,

The complete paper is now freely available, via the following link:

ncbi.nlm.nih.gov/pubmed/279...

Note that the findings reported in the Sampson et al. paper have not been universally accepted (and have yet to be reproduced). For example, see the second comment in the PubMed Commons section of the webpage (the comment by Claudiu Bandea).

Jeff

[park_bear in reply to jeffreyn]

Very interesting. Claudiu Bandea seems to be long on interesting ideas but short on facts, for example: sandwalk.blogspot.com/2013/...

HIs unreviewed paper "Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders" at biorxiv.org/content/biorxiv... is likewise. There is good reason to think the amyloid of Alzheimers is an immune response, as set forth here: ncbi.nlm.nih.gov/pmc/articl... , but to extend that idea to every neurodegenerative disease under the sun requires more evidence than he has put forth. His main citation in support of this role for alpha-synuclein is here fasebj.org/content/19/6/533... which says that extra cellular alpha-synuclein causes inflammation, but this falls way short of his contention that alpha-synuclein serves a useful role in the immune system.

[jeffreyn in reply to park_bear]

Thanks for the links.

Regarding his contention that alpha-synuclein serves a useful role in the immune system, there is also some more-recent support for this:

alzforum.org/news/research-...

Regarding the Sampson et al. paper, there has also been some criticism of aspects of the statistical analysis. It is unfortunate though, that the authors of this criticism have not posted their comments at PubMed Commons, and have chosen to remain anonymous:

pubpeer.com/publications/76...

[park_bear in reply to jeffreyn]

Well OK then. I find the alzforum piece persuasive, and the Sampson paper has similar implications. Still many unanswered questions but every piece of the puzzle helps.

[ddmagee1]

Very interesting! Gut bacteria studies have brought out many new theories on the initiation of neuro-degeneration, and other medical disease processes within the human body, additionally. Perhaps, only the tip of the iceberg has been explored. If this research will help, so that there will be a way to prevent neuro-degeneration from starting, at it’s origin, it would be an answer for hope, that so many have fought for over the years, who have been searching for a cure, an answer to the devastating neurodegenerative diseases, that afflict so many.

[M1tz1 in reply to ddmagee1]

Alzheimer's can now be prevented and even reversed. See Dr Dale Bredesen's newly published book 'The End of Alzheimer's'. Is there a way to reproduce pictures here? If so, I'll send a photo of the cover of his book. My husband, who now has Parkinson's, was released from his Alzheimer's using a combination of Dr Bredesen's protocol, Dr DavidPerlmutter's diet in his book 'Grain Brain' and Dr Mary Metcalf's findings on coconut oil. Dr Perlmutter believes that the same (ketogenic) diet is helpful in Parkinson's. I encountered a YouTube presentation of Dr Perlmutter's treatment of a PwP with intravenous Liposomal Glutathione; the patient was able to walk and talk with much improvement afterwards.

[Blackfeather]

Why is there not more discussion about fecal Microbiota transplantation therapy for PD and other illnesses? I guess there is not enough money in it. Tragic!

[jeffreyn in reply to Blackfeather]

Hi Blackfeather,

There is an "FMT for PD" trial due to (hopefully) start soon in Texas.

clinicaltrials.gov/show/NCT...

Jeff

[Blackfeather in reply to jeffreyn]

Jeff

Thanks for the info. Do you know what PRIM-DJ2727 is? Have you any info on this? Thanks

[jeffreyn in reply to Blackfeather]

My understanding of PRIM-DJ2727 comes from two phrases in the project description, namely "enteric-coated capsules" and "oral administration of a fecal suspension from healthy donors".

I've read elsewhere that "enteric-coated capsules" are designed to pass intact through the acidic environment of the stomach, and then to dissolve in the alkaline environment of the intestine.