Levodopa and Its Infused Gel Form Affect Gut Bacteria, May Promote Inflammation

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Levodopa, and especially levodopa/carbidopa intestinal gel (LCIG) — a formulation of levodopa and carbidopa infused directly into the intestines — can alter gut bacteria composition and metabolism, acting as drivers of bowel inflammation and possibly of disease progression in people with Parkinson’s disease, a study reported.

The study, “Gut microbiota and metabolome distinctive features in parkinson disease: Focus on levodopa and levodopa carbidopa intrajejunal gel,” was published in the European Journal of Neurology.

Recent studies have suggested that imbalances in the composition of gut bacteria might contribute to Parkinson’s progression.

Some studies also suggested that levodopa, a mainstay disease treatment, could affect gut bacteria composition. But none have “specifically addressed changes of the microbial community composition in PD [Parkinson’s disease] related to LD [levodopa] medication in detail,” the researchers wrote.

Yet, a recent study demonstrated that gut bacteria can process and convert levodopa into other substances, highlighting their key role in modulating the medication’s availability and effectiveness.

“These data suggest a complex interplay interaction between [gut bacteria] and disease progression, disease phenotype [symptoms] and antiparkinsonian medications, which still needs to be clarified,” they added.

Researchers investigated the potential impact of levodopa and LCIG on the composition and metabolism of gut bacteria in Parkinson’s patients.

As a first step, they collected stool samples from 107 patients being followed at two clinical centers in Italy, one in Cagliari and the other in Turin.

Researchers then isolated bacterial DNA from the stool samples and used next‐generation sequencing (a technique that allows scientists to “read” genetic information contained within DNA) to determine which species of bacteria were present in samples. A technique called gas chromatography mass spectrometry (GC‐MS) was used to identify metabolism byproducts in the stool samples.

Patients were divided into three groups, depending on the medications they were using at the time they participated in the study: the naïve group included 23 people not taking any antiparkinsonian medications, the LD group covered 46 patients who were on levodopa, and the LCIG group had remaining 38 patients being treated with levodopa/carbidopa intestinal gel.

No significant differences in the diversity of bacteria species were found between patients in the LD and LCIG groups. However, those naïve to treatment had a higher degree of diverse gut bacteria species compared with patients using either levodopa or LCIG.

Statistical analyses also revealed that patients in the LCIG group had a higher number of potentially harmful bacteria, those belonging to the Enterobacteriaceae family, the Escherichia, and Serratia genera, compared with LD group patients.

“Consequently, our results suggest that LCIG might share the potential negative mechanisms of LD [levodopa] on gut microbiota with a more detrimental effect,” the researchers wrote.

Several differences in gut bacteria composition were also found when comparing naïve group patients with those on antiparkinsonian medications. For instance, those taking levodopa had a lower number of bacteria species belonging to the Blautia and Lachnospirae genera compared to naïve patients.

LCIG group patients were found to have a higher number of bacteria belonging to the Proteobacteria phyllum and the Enterobacteriaceae family, and a lower number belonging to the Firmicutes phyllum, Lachnospiraceae family, and Blautia genus compared with naïve patients. 

Using GC‐MS, the researchers also discovered that stool samples collected from patients being treated with either levodopa or LCIG tended to have lower levels of anti-inflammatory metabolites, such as butyric acid and acetic acid, and higher levels of pro-inflammatory metabolism byproducts, including cadaverine.

“Our results suggest that LD and mostly LCIG might significantly influence the microbiota composition and host/bacteria metabolism acting as stressors in precipitating a specific inflammatory intestinal microenviroment, potentially related to the PD state and progression,” the researchers wrote.
They noted that additional studies in larger number of patients are needed to clarify how antiparkinsonian medications may affect gut bacteria composition and metabolism in people with Parkinson’s.