UMMS Affiliation

Department of Population and Quantitative Health Sciences; Department of Microbiology and Physiological Systems; UMass Center for Microbiome Research; Department of Neurology

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Digestive System | Microbiology | Musculoskeletal, Neural, and Ocular Physiology | Nervous System Diseases | Neurology | Neuroscience and Neurobiology


Background: The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed.

Methods: We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa. Motor impairment (MDS-UPDRS Part III), diet, and other patient characteristics were assessed. 16S rRNA gene amplicon sequencing was used to characterize the microbiota. We examined, cross-sectionally and longitudinally, the associations between Levodopa use and alpha and beta diversity and performed feature-wise, multivariate modeling to identify taxa associated longitudinally with Levodopa use and with improvement in motor function after Levodopa administration.

Results: We did not observe significant differences in alpha or beta diversity before vs. after initiation of Levodopa. In longitudinal feature-wise analyses, at the genus level, no taxa were significantly associated with Levodopa use after false discovery rate (FDR) correction (q < 0.05). We observed a marginally lower relative abundance of bacteria belonging to Clostridium group IV in PD patients who experienced a medium or large improvement in motor impairment in response to Levodopa compared to those with a small response [beta = -0.64 (SE: 0.18), p-trend: 0.00015 p-FDR: 0.019].

Conclusions: In this study, Levodopa was not associated with changes in microbiota composition in this longitudinal analysis. The association between abundance of Clostridium group IV and short-term motor symptom response to Levodopa is preliminary and should be investigated in larger, longer-term studies, that include a control group.


Levodopa, Parkinson's disease, Unified Parkinson's Disease Rating Scale, microbiome, motor function

Rights and Permissions

Copyright © 2021 Palacios, Hannoun, Flahive, Ward, Goostrey, Deb and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version



Palacios N, Hannoun A, Flahive J, Ward D, Goostrey K, Deb A, Smith KM. Effect of Levodopa Initiation on the Gut Microbiota in Parkinson's Disease. Front Neurol. 2021 Mar 4;12:574529. doi: 10.3389/fneur.2021.574529. PMID: 33746867; PMCID: PMC7970035. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in neurology

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.