Parkinson's Disease Medication Alters Small Intestinal Motility and Microbiota Composition in Healthy Rats!! Hmmm... how can we benefit?

[enjoy2013]

Hello...

I hope you are not suffering too much from the heat or from airconditionitis. I have been following this research group from the Netherlands since their Nature paper on bacterial tyrosine decarboxylase. Although their work is actually really interesting, and every time I read their paper it's really new stuff, I can't figure out how to use it for our benefit. Anybody has ideas? pubmed.ncbi.nlm.nih.gov/350...

I suppose that could be a reason to favor intranasal or subcutaneous therapies, and both Neuroderm and Abbvie could test their patients. But as long as we are treated with regular Ldopa...?

[Bolt_Upright]

"Parkinson’s disease (PD) is known to be associated with altered gastrointestinal function and microbiota composition. To date, the effect of PD medication on the gastrointestinal function and microbiota, at the site of drug absorption, the small intestine, has not been studied, although it may represent an important confounder in reported microbiota alterations observed in PD patients. To this end, healthy (non-PD) wild-type Groningen rats were employed and treated with dopamine, pramipexole (in combination with levodopa-carbidopa), or ropinirole (in combination with levodopa-carbidopa) for 14 sequential days. Rats treated with dopamine agonists showed a significant reduction in small intestinal motility and an increase in bacterial overgrowth in the distal small intestine. Notably, significant alterations in microbial taxa were observed between the treated and vehicle groups; analogous to the changes previously reported in human PD versus healthy control microbiota studies. These microbial changes included an increase in Lactobacillus and Bifidobacterium and a decrease in Lachnospiraceae and Prevotellaceae. Markedly, certain Lactobacillus species correlated negatively with levodopa levels in the systemic circulation, potentially affecting the bioavailability of levodopa. Overall, the study highlights a significant effect of PD medication intrinsically on disease-associated comorbidities, including gastrointestinal dysfunction and small intestinal bacterial overgrowth, as well as the gut microbiota composition. The results urge future studies to take into account the influence of PD medication per se when seeking to identify microbiota-related biomarkers for PD."

[Boscoejean in reply to Bolt_Upright]

so are they saying that levodopa use increases the chances of SIBO? The way they word this is not that easy to grasp exactly what they are saying here

[enjoy2013 in reply to Boscoejean]

Yes, that's what I understand, including from the experimental design which is smart, to treat healthy rats. But if we are already treated with L-dopa or dopa agonists, then what can we do as a treatment intervention? As personally, I experience wearing off and missed doses and I associate them to some level of gastroparesis. But maybe it is at the small intestine rather than stomach level. This matter is causing me a lot of off-time and dystonia over the day. I manage from all angles but it is still a problem.

[LAJ12345 in reply to Boscoejean]

Levodopa can make you constipated too. When they increased hubby’s dose he became so constipated even the laxative didn’t really work. He decreased the levodopa and came right again. Regular again. Proof by example, clinical trial of n=1. 🤣

I am not convinced it was bacteria related though as the improvement was quick after decreasing. I think the rigidity he suffered In the rest of his body from the levodopa was probably the same in his bowel. He needed to pee more too.

[Boscoejean in reply to LAJ12345]

so it is so rough when the attempt to get help leads to more issues

[enjoy2013 in reply to LAJ12345]

It may be that the constipation came together with the reason they augmented the ldopa dose

[LAJ12345 in reply to enjoy2013]

No he had never been constipated before, and has gone away again once he decreased levodopa again almost immediately.

[Bolt_Upright in reply to Bolt_Upright]

The way I read this, and a lot of it went over my head, it looked like they were saying the changes in the microbiome for PWP might be from the drugs and not from the PD.

"Notably, significant alterations in microbial taxa were observed between the treated and vehicle groups; analogous to the changes previously reported in human PD versus healthy control microbiota studies."

[enjoy2013 in reply to Bolt_Upright]

Yes indeed, that's what they have in mind, as they saw the change occuring in treated "healthy" animals .