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Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non\u2010optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation,\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein\u2010rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub\u2010optimal levodopa response, \u2018delayed on\u2019 or \u2018no on\u2019 phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non\u2010oral therapies to bypass the GI tract.\n                  <\/jats:p>","DOI":"10.1111\/ene.15734","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T06:30:59Z","timestamp":1675924259000},"page":"1465-1480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Valentina","family":"Leta","sequence":"first","affiliation":[{"name":"Parkinson's Foundation Center of Excellence at King's College Hospital  London UK"},{"name":"Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London and National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre Institute of 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