A gut-brain link for Parkinson’s gets a closer look The m

[antares4141]

https://www.sciencenews.org/article...6Ib2lxtQxn2uq0GuIDkCvqbxLWbzxcN1xFEl4An46L0ag

 

[Belbyr]

I've seen more article come out about this. I think they are on to something...

 

[ljimbo423]

Abstract
In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha‐synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non‐motor symptom in PD and often precedes the onset of motor symptoms by years.

Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve.

The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1–V3 regions of the bacterial 16S ribosomal RNA gene.

Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders.

On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD.

A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty.

These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker. © 2014 International Parkinson and Movement Disorder Society

I am fairly convinced that an altered gut microbiome is at least a trigger, if the the cause of many diseases. That's why this statement from the abstract rings so true for me-

Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non‐motor symptom in PD and often precedes the onset of motor symptoms by years.

 

[Belbyr]

This makes a lot of sense, I hope they can come to a conclusion quickly.

 

[kangaSue]

I saw another interesting line of thought on the gut-brain axis in connection with Alzheimers and Parkinson's. It's known transcranial Photobiomodulation (PBM - also known as low-level laser (or light) therapy (LLLT)) can help with reducing brain hypoperfusion but in one mouse study (which I can't find any reference paper for), the light directed onto (or maybe into) the gut also increased brain perfusion.

It's not known yet what mechanism is involved for this when it's gut directed but Photobiomodulation has been shown to also improve on RBC deformability (which improves microvascular blood flow) so it could be improving the intestinal microvascular blood flow too. That then could mean also that greater gut microvascular perfusion can reduce intestinal permeability and maybe a consequence of that improves on the gut bacterial balance and hence, the gut-brain axis too. Food for thought.

 

[Jackb23]

They have even been able to take the microbiome from a rat with PD and upon transfer, the new rat now displays PD symptoms.

 

[percyval577]

Ever my opinion is it´s a consequence. More difficult to get a clue though.

 

[Jackb23]

Ever my opinion is it´s a consequence. More difficult to get a clue though.

Anything in particular that gives you that hunch?

 

[JES]

Ever my opinion is it´s a consequence. More difficult to get a clue though.

It can't be a consequence if the healthy rat that gets the microbiome from the sick rat also then gets sick.

 

[percyval577]

@Jackb23 , @JES . The idea is that this microbiome produces molecules which would be needed and used by the body.

This - such a difficulty needed to be admitted - would aquire though that there is a regulation of the gut microbiome by the body, a) directly the microbiome to some extent or b) the pass through of bacteria or their products.

I know that this looks very complicate. But I find it rather unlikly that diseases simpley would develope because of the - enourmes though - microbiome in the gut.

I think it was 10% of Parkinson cases that have been shown to be genetically caused, whereas the cause of the most cases is still unknown. Yes, here raises the possibility these cases would be caused by the gut microbiome. I hope they looked at these 10%, did they?

In case of our disease it has also been shown that the gut microbiome , and even the mouth microbiome, is altered, and even it could be related to the severity if i am remembering right. This year a similar result for depression has been published.
Now, there are influences on depression which do not directly influence the microbiome. I myself are improving from a diet of low manganese, which can be understood as an influence on microglia. I admit that there should be a cyrkle involved, how important ever it may be.

 

[Belbyr]

https://www.sciencenews.org/article/parkinsons-disease-gut-microbes-brain-link

 

[percyval577]

This year a similar result for depression has been published.
Now, there are influences on depression which do not directly influence the microbiome

This is not true, sorry for that. The study I thought to referr to is:
Pan, Xia et al 2018: "Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitter: a target metabolomics study"

 

[Jackb23]

This is not true, sorry for that. The study I thought to referr to is:
Pan, Xia et al 2018: "Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitter: a target metabolomics study"

I’ll leave you with this:

REM sleep disorder is characterized by sleep paralysis and excessive motor behaviors that results in shouting and violent body movements. Interestingly enough, people that are diagnosed with REM Sleep Behavior Disorder are often (80-90%) later diagnosed with neurodegenerative diseases within 15 years. The most common of these neurodegenerative diseases is synucleinopathies (think Parkinson’s essentially). How can REM Sleep Behavior Disorder be such a strong predictive factor? Well it is now highly regarded that they are not separate disorders. Instead, the sleep behavior disorder is the first sign/symptom. Interesting enough, what some researchers believe is that pathogenic alpha-Synuclein travels along vagus nerve afferents. Once these pathogens reach the brain the first thing they hit is the nucleus of the solitary tract (NST) and the dorsal motor nucleus of the vagus nerve. To tie this all together, the NST and the dorsal motor nucleus sit in extremely close proximity to the cells that control REM sleep. These cells slowly spread the pathogen along and eventually reach the motor neurons and the cortex which is why you see the motor and cognitive issues. This would support the idea that Parkinson’s starts in the gut and fits the classical model of Parkinson’s.

Main Source: https://www.ncbi.nlm.nih.gov/m/pubmed/29161567/

 

[Jackb23]

Also, while I understand that the picture is much larger than this simple fact, I find it extremely amusing that 80% of all vagus nerves are afferent and only 20% are efferent. This would seem to support the idea that the gut may have a larger role in giving the brain information than the brain in giving the gut information. I also understand that the brain may control the gut through indirect consequences such as CRH in the HPA axis.

 

[percyval577]

This would seem to support the idea that the gut may have a larger role in giving the brain information than the brain in giving the gut information.

I don´t hope so!

I find it extremely amusing that 80% of all vagus nerves are afferent and only 20% are efferent.

It took me a while until I understood that you are not talking about the mentioned alpha-synuclein protein. The protein perhaps wouldn´t care about afferents or efferents, if not interested in traffics.

Humour aside.
I mainly came up with the idea of a request of products because the body seems to me to be a webb, and even the science has developed rapidly in the past 20 years and with a lot of comfortable succes, the most of the picture is still unknown. And in our case eg there are some hints that the gut would not be the only (underlying) cause (there have been outbreaks, and if the gut theory would be true it needed to explain how a rapid altering of the gut microbiome would have taken place, including the consequencies). Also there are influences and even recoveries known, and especially in the last case I was wondering if this could be explained by an influence on the gut.
However, I hope for the sake of PWPD that the answere would be as simple as the guess, "- still a big if -" though. I don´t know how good the guesses I have read on some different causes of "Parkinson´s diseases" are. Maybe there is a request for the "misfolded" alpha-synuclein,?? “The question is, and it’s still an outstanding question, what is it that these bacteria are producing that is, at least in animals, causing alpha-synuclein to form amyloids?” (quote from the webside, quite at the end).

I admit that the gut might be an interesting or (sometimes?) an important factor.

 

[Jackb23]

I don´t hope so!

It took me a while until I understood that you are not talking about the mentioned alpha-synuclein protein. The protein perhaps wouldn´t care about afferents or efferents, if not interested in traffics.

Humour aside.
I mainly came up with the idea of a request of products because the body seems to me to be a webb, and even the science has developed rapidly in the past 20 years and with a lot of comfortable succes, the most of the picture is still unknown. And in our case eg there are some hints that the gut would not be the only (underlying) cause (there have been outbreaks, and if the gut theory would be true it needed to explain how a rapid altering of the gut microbiome would have taken place, including the consequencies). Also there are influences and even recoveries known, and especially in the last case I was wondering if this could be explained by an influence on the gut.
However, I hope for the sake of PWPD that the answere would be as simple as the guess, "- still a big if -" though. I don´t know how good the guesses I have read on some different causes of "Parkinson´s diseases" are. Maybe there is a request for the "misfolded" alpha-synuclein,?? “The question is, and it’s still an outstanding question, what is it that these bacteria are producing that is, at least in animals, causing alpha-synuclein to form amyloids?” (quote from the webside, quite at the end).

I admit that the gut might be an interesting or (sometimes?) an important factor.

Alpha-synuclein is a type of synucleinopathy

I don´t hope so!

It took me a while until I understood that you are not talking about the mentioned alpha-synuclein protein. The protein perhaps wouldn´t care about afferents or efferents, if not interested in traffics.

Humour aside.
I mainly came up with the idea of a request of products because the body seems to me to be a webb, and even the science has developed rapidly in the past 20 years and with a lot of comfortable succes, the most of the picture is still unknown. And in our case eg there are some hints that the gut would not be the only (underlying) cause (there have been outbreaks, and if the gut theory would be true it needed to explain how a rapid altering of the gut microbiome would have taken place, including the consequencies). Also there are influences and even recoveries known, and especially in the last case I was wondering if this could be explained by an influence on the gut.
However, I hope for the sake of PWPD that the answere would be as simple as the guess, "- still a big if -" though. I don´t know how good the guesses I have read on some different causes of "Parkinson´s diseases" are. Maybe there is a request for the "misfolded" alpha-synuclein,?? “The question is, and it’s still an outstanding question, what is it that these bacteria are producing that is, at least in animals, causing alpha-synuclein to form amyloids?” (quote from the webside, quite at the end).

I admit that the gut might be an interesting or (sometimes?) an important factor.

I think it’s funny that you have a gut feeling that it’s starting in the brain.

 

[percyval577]

@Jackb23, as I understand it:
Alpha-synuclein is a protein in vertebrates (eg humans) - and it is coded in a gene (SNCA-gene)
If there are special muations then a synucleinopathy can occure (the protein is misfolded, built up wrongly).

The article says a synuclein from the intestinal may become misfolded during the passage through the vagus nerve.
Maybe there is even some purpose, and in a low amount these misfolded proteins are normal? -
Then it could be subject to a regulation.

I only try to think logically. The most details are not known, generel speaking.
Maybe the gut theory will proof to be right, funnily.

 

[ljimbo423]

I think it’s funny that you have a gut feeling that it’s starting in the brain.

That is funny!!

 

[ljimbo423]

There is a strong connection to the gut in ME/CFS also. I have links to 5-6 studies that show increased levels of LPS in the bloodstream of CFS patients over healthy controls. This shows ongoing leaky gut and passage of LPS into the bloodstream.

This is a quote from a study done on CFS patients with "Bacterial Therapy". From what I understand, they cultured 13 healthy bacterial strains from healthy stool donors and infused them into the gut of CFS patients. These were the results-

Results: 35/60 patients who underwent initial bacteriotherapy responded to treatment. 10/15 patients who failed this course were offered a secondary transcolonoscopic infusion followed by a rectal infusion or an oral course of cultured bacteria.

Of these 7/10 responded, giving a total of 42/60 (70%) patients who responded to treatment. Contact was achieved with 12 patients after 15-20 year follow-up.

Complete resolution of symptoms was maintained in seven of the twelve patients and 5/12 did not experience recurrence for approximately 1.5-3 years post bacteriotherapy.

Conclusion: Bacteriotherapy achieves initial success rate of 70% in CFS and a 58% sustained response.

Given that manipulation of the colonic microbiota improved CFS symptoms, bacteriotherapy for CFS warrants further investigation and may provide further insight into a possible etiology of CFS.

Since 58% of the CFS patients had a Complete resolution of symptoms after 15-20 years.

It makes really good sense to me that there CFS started in their gut and was reversed by re-balancing their gut bacteria with Bacterial Therapy and allowing their leaky gut to heal. Which stopped their symptoms and their ME/CFS.

Link to study

 

[percyval577]

Thank you for the study and the link, @ljimbo423 .
But the study says also:

Abstract: Introduction: Chronic Fatigue Syndrome (CFS) has a complex and multifactorial etiology making treatment and definitive diagnosis, currently made through exclusion, difficult.

Also the outcomes might indicate that the gut might be part of a larger cycle.