Microbiota-mediated effects of Parkinson’s disease medications on Parkinsonian non-motor symptoms in male transgenic mice
Why this work is in the frame
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Bibliographic record
Abstract
ABSTRACT Parkinson’s disease (PD) is characterized by motor symptoms and a loss of dopaminergic neurons, as well as a variety of non-motor symptoms, including constipation, depression, and anxiety. Recently, evidence has also accumulated for a link between gut microbiota and PD. Most PD patients are on dopamine replacement therapy, primarily a combination of L-DOPA and carbidopa; however, the effect of these medications on the microbiota and non-motor symptoms in PD is still unclear. In this study, we explored the effects of chronic oral treatment with L-DOPA plus carbidopa (LDCD) on the gut microbiota and non-motor symptoms in males of a transgenic mouse model of PD (dbl-PAC-Tg( SNCA A53T ); Snca -/-). To further test whether the effects of these PD medications were mediated by the gut microbiota, oral antibiotic treatment (Abx; vancomycin and neomycin) was included both with and without concurrent LDCD treatment. Post-treatment, the gastrointestinal, motor, and behavioral phenotypes were profiled, and fecal, ileal, and jejunal samples were analyzed for gut microbiota composition by 16S sequencing. LDCD treatment was found to improve symptoms of constipation and depression in this model, concurrent with increases in Turicibacter abundance in the ileum. Abx treatment worsened the symptoms of constipation, possibly through decreased levels of short-chain fatty acids and disrupted gut barrier function. LDCD + Abx treatment showed an interaction effect on behavioral symptoms that was also associated with ileal Turicibacter levels. This study demonstrates that, in a mouse model, PD medications and antibiotics affect PD-related non-motor symptoms potentially via the gut microbiota. IMPORTANCE The motor symptoms of Parkinson’s disease (PD) are caused by a loss of dopamine-producing neurons and are commonly treated with dopamine replacement therapy (L-DOPA plus carbidopa). PD has also been associated with altered gut microbiota composition. However, the effects of these PD medications on PD-related non-motor symptoms and the gut microbiota have not been well characterized. This study uses a transgenic mouse model of PD to help resolve medication-induced microbiota alterations from those that are potentially disease relevant within a PD context, and explores how long-term treatment may interact with the gut microbiota to impact non-motor symptoms.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it