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While Enterococcus faecalis (E. faecalis)-derived tyrosine decarboxylases (tyrDCs) are known to decarboxylate levodopa (L-dopa), compromising systemic bioavailability, the causal mechanisms underlying microbiota-mediated pharmacodynamic variability remain unresolved. In our study, we employed antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to interrogate microbiota-L-dopa interactions in MPTP-induced Parkinson\u2019s disease (PD) mice. The study demonstrated that antibiotic-mediated microbiota depletion enhances L-dopa bioavailability and striatal dopamine (DA) level, correlating with improved motor function. To dissect clinical heterogeneity in the L-dopa response, PD patients were stratified into moderate responders and good responders following standardized L-dopa challenges. In vitro bioconversion assays revealed greater L-dopa-to-DA conversion in fecal samples from moderate responders versus good responders. FMT experiments confirmed mice receiving good-responder microbiota exhibited enhanced L-dopa bioavailability, higher striatal DA concentrations, and a heightened therapeutic effect of L-dopa relative to moderate-responder recipients. Collectively, our study provided evidence that the gut microbiota directly modulates L-dopa metabolism and microbial composition determines interindividual therapeutic heterogeneity. Targeted microbial modulation\u2014through precision antibiotics or donor-matched FMT\u2014is a viable strategy to optimize PD pharmacotherapy, supporting the potential for microbiota-targeted adjuvant therapies in PD management.<\/jats:p>","DOI":"10.3390\/ijms26115282","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T09:22:41Z","timestamp":1748596961000},"page":"5282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted Gut Microbiota Modulation Enhances Levodopa Bioavailability and Motor Recovery in MPTP Parkinson\u2019s Disease Models"],"prefix":"10.3390","volume":"26","author":[{"given":"Penghui","family":"Ai","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-0868","authenticated-orcid":false,"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-6413","authenticated-orcid":false,"given":"Chengjun","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-4525","authenticated-orcid":false,"given":"Xiaodong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/archneur.1971.00490010049007","article-title":"Metabolism of Levodopa in Patients with Parkinson\u2019s Disease: Radioactive and Fluorometric Assays","volume":"25","author":"Morgan","year":"1971","journal-title":"Arch. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cacabelos, R. (2017). Parkinson\u2019s Disease: From Pathogenesis to Pharmacogenomics. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030551"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eaau6323","DOI":"10.1126\/science.aau6323","article-title":"Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism","volume":"364","author":"Bess","year":"2019","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Muleiro Alvarez, M., Cano-Herrera, G., Osorio Mart\u00ednez, M.F., Vega Gonzales-Portillo, J., Monroy, G.R., Murguiondo P\u00e9rez, R., Torres-R\u00edos, J.A., van Tienhoven, X.A., Garibaldi Bernot, E.M., and Esparza Salazar, F. (2024). A Comprehensive Approach to Parkinson\u2019s Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137183"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Caputi, V., and Giron, M.C. (2018). Microbiome-Gut-Brain Axis and Toll-like Receptors in Parkinson\u2019s Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061689"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s40262-021-01032-y","article-title":"Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability","volume":"60","author":"Tsunoda","year":"2021","journal-title":"Clin. Pharmacokinet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1126\/science.1235872","article-title":"Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta","volume":"341","author":"Haiser","year":"2013","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1124\/dmd.118.084772","article-title":"Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites","volume":"47","author":"Guo","year":"2019","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lee, J.R., Muthukumar, T., Dadhania, D., Taur, Y., Jenq, R.R., Toussaint, N.C., Ling, L., Pamer, E., and Suthanthiran, M. (2015). Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122399"},{"key":"ref_12","first-page":"1","article-title":"Colonization-Induced Host-Gut Microbial Metabolic Interaction","volume":"2","author":"Berger","year":"2011","journal-title":"mBio"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bj\u00f6rkholm, B., Bok, C.M., Lundin, A., Rafter, J., Hibberd, M.L., and Pettersson, S. (2009). Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006958"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"van Kessel, S.P., de Jong, H.R., Winkel, S.L., van Leeuwen, S.S., Nelemans, S.A., Permentier, H., Keshavarzian, A., and El Aidy, S. (2020). Gut bacterial deamination of residual levodopa medication for Parkinson\u2019s disease. BMC Biol., 18.","DOI":"10.1186\/s12915-020-00876-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/ana.1267","article-title":"Helicobacter pylori-induced reduction of acute levodopa absorption in Parkinson\u2019s disease patients","volume":"50","author":"Pierantozzi","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1002\/mds.22190","article-title":"Helicobacter pylori infection and motor fluctuations in patients with Parkinson\u2019s disease","volume":"23","author":"Lee","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/ajcn\/22.3.292","article-title":"Intestinal absorption of amino acids. Current concepts","volume":"22","author":"Spencer","year":"1969","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2443","DOI":"10.1212\/WNL.0000000000201204","article-title":"Association Between Microbial Tyrosine Decarboxylase Gene and Levodopa Responsiveness in Patients with Parkinson Disease","volume":"99","author":"Zhang","year":"2022","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40263-024-01073-4","article-title":"The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications","volume":"38","author":"Menozzi","year":"2024","journal-title":"CNS Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2454937","DOI":"10.1080\/19490976.2025.2454937","article-title":"Pharmacomicrobiomics: A new field contributing to optimizing drug therapy in Parkinson\u2019s disease","volume":"17","author":"Zhang","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00415-010-5728-8","article-title":"Pharmacokinetics of levodopa","volume":"257","author":"Contin","year":"2010","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, L., Xiong, N., Huang, J., Guo, S., Liu, L., Han, C., Zhang, G., Jiang, H., Ma, K., and Xia, Y. (2017). Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson\u2019s Disease. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00206"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/mds.27610","article-title":"Continuous versus intermittent oral administration of levodopa in Parkinson\u2019s disease patients with motor fluctuations: A pharmacokinetics, safety, and efficacy study","volume":"34","author":"Torti","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/ene.15734","article-title":"Gastrointestinal barriers to levodopa transport and absorption in Parkinson\u2019s disease","volume":"30","author":"Leta","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1002\/mds.25522","article-title":"The role of small intestinal bacterial overgrowth in Parkinson\u2019s disease","volume":"28","author":"Fasano","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.parkreldis.2014.02.019","article-title":"Small intestinal bacterial overgrowth in Parkinson\u2019s disease","volume":"20","author":"Tan","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s100720170061","article-title":"Reduced L-dopa absorption and increased clinical fluctuations in Helicobacter pylori-infected Parkinson\u2019s disease patients","volume":"22","author":"Pierantozzi","year":"2001","journal-title":"Neurol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1212\/01.wnl.0000221672.01272.ba","article-title":"Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations","volume":"66","author":"Pierantozzi","year":"2006","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41467-019-08294-y","article-title":"Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson\u2019s disease","volume":"10","author":"Frye","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1021\/cn5001759","article-title":"Classics in Chemical Neuroscience: Levodopa","volume":"5","author":"Whitfield","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/phar.2428","article-title":"Potential Implications of Gut Microbiota in Drug Pharmacokinetics and Bioavailability","volume":"40","author":"Flowers","year":"2020","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/ana.10189","article-title":"Evolution of the response to levodopa during the first 4 years of therapy","volume":"51","author":"Nutt","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S521","DOI":"10.1002\/mds.22049","article-title":"Levodopa unresponsive symptoms in Parkinson disease","volume":"23","author":"Sethi","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"He, X., Lai, Y., Mo, C., Zhang, Y., Ai, P., Xu, S., Qian, Y., Xiao, Q., and Yang, X. (2024). Association between Fecal Bile Acids and Levodopa Response in Patients with Parkinson\u2019s Disease. Microorganisms, 12.","DOI":"10.3390\/microorganisms12071432"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/jcph.1096","article-title":"MAO-B and COMT Genetic Variations Associated with Levodopa Treatment Response in Patients with Parkinson\u2019s Disease","volume":"58","author":"Sampaio","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.parkreldis.2013.10.017","article-title":"Dopa-decarboxylase gene polymorphisms affect the motor response to l-dopa in Parkinson\u2019s disease","volume":"20","author":"Devos","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1093\/brain\/awv063","article-title":"Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson\u2019s disease","volume":"138","author":"Moreau","year":"2015","journal-title":"Brain"},{"key":"ref_38","first-page":"100333","article-title":"Contribution of dopaminergic polymorphisms to levodopa treatment response and drug concentration in Chinese patients with Parkinson\u2019s disease","volume":"12","author":"He","year":"2025","journal-title":"Clin. Park. Relat. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eaag2770","DOI":"10.1126\/science.aag2770","article-title":"Chemical transformation of xenobiotics by the human gut microbiota","volume":"356","author":"Koppel","year":"2017","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrmicro.2016.17","article-title":"The microbial pharmacists within us: A metagenomic view of xenobiotic metabolism","volume":"14","author":"Spanogiannopoulos","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Ning, J., Bao, X.-Q., Shang, M., Ma, J., Li, G., and Zhang, D. (2021). Fecal microbiota transplantation protects rotenone-induced Parkinson\u2019s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome, 9.","DOI":"10.1186\/s40168-021-01107-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbi.2018.02.005","article-title":"Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson\u2019s disease mice: Gut microbiota, glial reaction and TLR4\/TNF-\u03b1 signaling pathway","volume":"70","author":"Sun","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12934-021-01589-0","article-title":"Evaluation of fecal microbiota transplantation in Parkinson\u2019s disease patients with constipation","volume":"20","author":"Kuai","year":"2021","journal-title":"Microb. Cell Factories"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e22035","DOI":"10.1097\/MD.0000000000022035","article-title":"Fecal microbiota transplantation therapy for Parkinson\u2019s disease: A preliminary study","volume":"99","author":"Xue","year":"2020","journal-title":"Medicine"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sadowski, K., Zaj\u0105c, W., Milanowski, \u0141., Koziorowski, D., and Figura, M. (2024). Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson\u2019s Disease: A Review of Inflammatory Markers and Potential Effects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147741"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez Rojo, N., Blanco Ben\u00edtez, M., Cava, R., Fuentes, J.M., Canales Cort\u00e9s, S., and Gonz\u00e1lez Polo, R.A. (2024). Convergence of Neuroinflammation, Microbiota, and Parkinson\u2019s Disease: Therapeutic Insights and Prospects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111629"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhong, Z., Ye, M., and Yan, F. (2023). A review of studies on gut microbiota and levodopa metabolism. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1046910"},{"key":"ref_48","first-page":"165","article-title":"Parkinson\u2019s Disease Society Brain Bank, London: Overview and research","volume":"39","author":"Daniel","year":"1993","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1002\/mds.23429","article-title":"Systematic review of levodopa dose equivalency reporting in Parkinson\u2019s disease","volume":"25","author":"Tomlinson","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e65088","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-levelprofiling of diverse microbial communities with bioBakery 3","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hyatt, D., Chen, G.L., Locascio, P.F., Land, M.L., Larimer, F.W., and Hauser, L.J. (2010). Prodigal: Prokaryotic gene recognition and translation initiation site identification. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-119"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/s41467-024-45473-y","article-title":"Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17\/Treg cell balance axis","volume":"15","author":"Jia","year":"2024","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:44:08Z","timestamp":1760031848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115282"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115282","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}