Parkinson’s Disease Medication Alters Small Intestinal Motility and Microbiota Composition in Healthy Rats

Kessel, Sebastiaan P. van; Bullock, Amber; Dijk, Gertjan van; Aidy, Sahar El

doi:10.1128/msystems.01191-21

Cited by 22 publications

(16 citation statements)

References 78 publications

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“…However, the drawback of oral administration lies in the unavoidable intestinal absorption of SCFAs, may be influenced by various factors including gastrointestinal symptoms in patients with PD, dysbiosis of the intestinal microbiota, or drug interference, thereby affecting their absorption rate. [138][139][140] Furthermore, sustained or periodic intravenous infusion of SCFAs may lead to side effects such as venous inflammation. [141] Another approach involves enhancing dietary patterns, such as structuring a high dietary fiber intake, to promote anaerobic fermentation of dietary fiber by gut microbiota and generate SCFAs.…”

Section: Therapeutic Implications Of Scfas For Pd Managementmentioning

confidence: 99%

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

Liu,

Chen,

2024

Medicine

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Short-chain fatty acids (SCFAs) are, the metabolic byproducts of intestinal microbiota that, are generated through anaerobic fermentation of undigested dietary fibers. SCFAs play a pivotal role in numerous physiological functions within the human body, including maintaining intestinal mucosal health, modulating immune functions, and regulating energy metabolism. In recent years, extensive research evidence has indicated that SCFAs are significantly involved in the onset and progression of Parkinson disease (PD). However, the precise mechanisms remain elusive. This review comprehensively summarizes the progress in understanding how SCFAs impact PD pathogenesis and the underlying mechanisms. Primarily, we delve into the synthesis, metabolism, and signal transduction of SCFAs within the human body. Subsequently, an analysis of SCFA levels in patients with PD is presented. Furthermore, we expound upon the mechanisms through which SCFAs induce inflammatory responses, oxidative stress, abnormal aggregation of alpha-synuclein, and the intricacies of the gut-brain axis. Finally, we provide a critical analysis and explore the potential therapeutic role of SCFAs as promising targets for treating PD.

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Section: Therapeutic Implications Of Scfas For Pd Managementmentioning

confidence: 99%

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

Liu,

Chen,

2024

Medicine

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“…Of note, this study demonstrated that bacterial function could shift in response to drugs without a change in taxon abundance, thus highlighting the need for using metrics other than abundance when investigating the impact of drugs. Importantly, the interaction between the microbiome and drugs is bidirectional, with many studies clearly demonstrating that gut microbes can also actively metabolize 9,10,11,12 , and under certain circumstances bioaccumulate 13 , pharmaceutical drugs. While several studies to date have shed light on the nature and extent of microbe-driven drug transformations 9,10,11 , mechanistic details for human-targeted drug impact on the microbiome remain to be elucidated.…”

Section: Mainmentioning

confidence: 99%

The Parkinson’s drug entacapone disrupts gut microbiome homeostasis via iron sequestration

Pereira,

Ge,

Kristensen

et al. 2023

Preprint

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Increasing evidence shows that many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, much less is known about the mechanisms by which drugs target the microbiome and how drugs affect microbial function. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single cell chemical imaging to investigate the impact of two widely prescribed nervous system targeted drugs on the gut microbiome.Ex vivosupplementation of physiologically relevant concentrations of entacapone or loxapine succinate to faecal samples significantly impacted the abundance of up to one third of the microbial species present. Importantly, we demonstrate that the impact of these drugs on microbial metabolism is much more pronounced than their impact on abundances, with low concentrations of drugs reducing the activity, but not the abundance of key microbiome members likeBacteroides, RuminococcusorClostridiumspecies. We further demonstrate that entacapone impacts the microbiome due to its ability to complex and deplete available iron, and that microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Remarkably, entacapone-induced iron starvation selected for iron-scavenging organisms carrying antimicrobial resistance and virulence genes. Collectively, our study unveils the impact of two under-investigated drugs on whole microbiomes and identifies metal sequestration as a mechanism of drug-induced microbiome disturbance.

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“…The authors proposed that one mechanism that may explain the delay in gastric emptying in this population was the effect of levodopa on dopaminergic receptors in the stomach and that this might be exacerbated by the use of a dopa decarboxylase inhibitor, which would increase levodopa concentrations further, resulting in an effect on drug delivery and efficacy. A study in healthy rats showed that dopamine agonist treatment resulted in a reduction in small intestinal motility and an increase in bacterial overgrowth in the distal small intestine ( van Kessel et al, 2022 ). There was also an increase in the amount of small bowel bacteria ( Lactobacillus species), which correlated negatively with levodopa levels in the systemic circulation, suggesting an effect on the bioavailability of levodopa.…”

Section: Gastroparesis In Parkinson’s Diseasementioning

confidence: 99%

Management of dysphagia and gastroparesis in Parkinson’s disease in real-world clinical practice – Balancing pharmacological and non-pharmacological approaches

Bhidayasiri

Phuenpathom

Tan

et al. 2022

Front. Aging Neurosci.

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Gastrointestinal (GI) issues are commonly experienced by patients with Parkinson’s disease (PD). Those that affect the lower GI tract, such as constipation, are the most frequently reported GI problems among patients with PD. Upper GI issues, such as swallowing dysfunction (dysphagia) and delayed gastric emptying (gastroparesis), are also common in PD but are less well recognized by both patients and clinicians and, therefore, often overlooked. These GI issues may also be perceived by the healthcare team as less of a priority than management of PD motor symptoms. However, if left untreated, both dysphagia and gastroparesis can have a significant impact on the quality of life of patients with PD and on the effectiveness on oral PD medications, with negative consequences for motor control. Holistic management of PD should therefore include timely and effective management of upper GI issues by utilizing both non-pharmacological and pharmacological approaches. This dual approach is key as many pharmacological strategies have limited efficacy in this setting, so non-pharmacological approaches are often the best option. Although a multidisciplinary approach to the management of GI issues in PD is ideal, resource constraints may mean this is not always feasible. In ‘real-world’ practice, neurologists and PD care teams often need to make initial assessments and treatment or referral recommendations for their patients with PD who are experiencing these problems. To provide guidance in these cases, this article reviews the published evidence for diagnostic and therapeutic management of dysphagia and gastroparesis, including recommendations for timely and appropriate referral to GI specialists when needed and guidance on the development of an effective management plan.

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Parkinson’s Disease Medication Alters Small Intestinal Motility and Microbiota Composition in Healthy Rats

Cited by 22 publications

References 78 publications

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

The Parkinson’s drug entacapone disrupts gut microbiome homeostasis via iron sequestration

Management of dysphagia and gastroparesis in Parkinson’s disease in real-world clinical practice – Balancing pharmacological and non-pharmacological approaches

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