Bacterial Butyrate in Parkinson's Disease Is Linked to Epigenetic Changes and Depressive Symptoms, 2022, Xie et al

Abstract

Background
The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers.

Objectives
Here, we investigate whether the changes in the gut microbiome and associated metabolites are related to PD symptoms and epigenetic markers in leucocytes and neurons.

Methods
Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified genome-wide DNA methylation by targeted bisulfite sequencing.

Results
We show that lower fecal butyrate and reduced counts of genera Roseburia, Romboutsia, and Prevotella are related to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA regions in PD overlap with those altered in gastrointestinal (GI), autoimmune, and psychiatric diseases.

Conclusions
Decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms. PD shares common butyrate-dependent epigenetic changes with certain GI and psychiatric disorders, which could be relevant for their epidemiological relation.

Open access, https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29128

 

I can't find any actual definition of what they mean by "depressive symptoms". It seems they used something called the GDS-15, geriatric depression symptoms, which doesn't ask about symptoms. The only one that is even relevant to symptoms is asking about being "full of energy", but obviously a simple binary answer means nothing here, even more so on a geriatric population, even more so in a geriatric population with a highly disabling chronic disease.

Being bored is obviously not a medical symptom. There are huge issues with basic vocabulary in everything dealing with mental health if they confound asking about medical symptoms with ridiculous questions like those. It's obvious to see why the entire field is stuck going around in loops chasing their own shadows.

And I have seen someone deteriorate for years with PD. My maternal grandmother had it for years along with polyneuropathy. I think it's perfectly reasonable to answer yes on most of those questions and it's just as rational an answer as asking someone who has lived in poverty their whole life whether they feel financially secure.

1. Are you basically satisfied with your life? yes no
2. Have you dropped many of your activities and interests? yes no
3. Do you feel that your life is empty? yes no
4. Do you often get bored? yes no
5. Are you in good spirits most of the time? yes no
6. Are you afraid that something bad is going to happen to you? yes no
7. Do you feel happy most of the time? yes no
8. Do you often feel helpless? yes no
9. Do you prefer to stay at home, rather than going out and doing things? yes no
10. Do you feel that you have more problems with memory than most? yes no
11. Do you think it is wonderful to be alive now? yes no
12. Do you feel worthless the way you are now? yes no
13. Do you feel full of energy? yes no
14. Do you feel that your situation is hopeless? yes no
15. Do you think that most people are better off than you are? yes no