{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:27:09Z","timestamp":1789140429453,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gut\u2010brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease\u2010modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterised 77 participants with diagnosed\u2010PD, 113 without, by dietary\/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines\/chemokines, clinical phenotype including colonic transit time. Complete\u2010linkage hierarchical cluster analysis of metabolites discriminant for PD\u2010status was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Longer colonic transit\u00a0was linked to deficits in faecal short\u2010chain\u2010fatty acids outside PD, to a \u2018tryptophan\u2010containing metabolite cluster\u2019 overall. Phenotypic cluster analysis\u00a0aggregated colonic transit with brady\/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan\u2010cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole\u2010ring compound (anti\u2010fungals) and vitamin B3 (anti\u2010inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes\/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid\u2010cluster deficit was linked to (well\u2010recognised) lower caffeine and alcohol intakes, tryptophan\u2010cluster deficit to higher maltose intake. Free\u2010sugar intake was increased in PD, maltose intake being 63% higher (<jats:italic>p<\/jats:italic> = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [<jats:italic>p<\/jats:italic> = .001, adjusted for proton\u2010pump inhibitors (<jats:italic>p<\/jats:italic> = .001)], with 16% of PD\u2010probands exceeding a cut\u2010point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut\u2010point.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response\u00a0syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1152","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:19:45Z","timestamp":1672629585000},"source":"Crossref","is-referenced-by-count":19,"title":["Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome"],"prefix":"10.1002","volume":"13","author":[{"given":"Aisha","family":"Augustin","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"},{"name":"The Maudsley Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien Le","family":"Guennec","sequence":"additional","affiliation":[{"name":"NMR Facility King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chianna","family":"Umamahesan","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"},{"name":"The Maudsley Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"Kendler\u2010Rhodes","sequence":"additional","affiliation":[{"name":"Nutritional Sciences King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind M.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"},{"name":"The Maudsley Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Chekmeneva","sequence":"additional","affiliation":[{"name":"National Phenome Centre Imperial College London  London UK"},{"name":"Section of Bioanalytical Chemistry Imperial College London  London UK"},{"name":"Department of Metabolism Digestion and Reproduction Imperial College, London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panteleimon","family":"Takis","sequence":"additional","affiliation":[{"name":"National Phenome Centre Imperial College London  London UK"},{"name":"Section of Bioanalytical Chemistry Imperial College London  London UK"},{"name":"Department of Metabolism Digestion and Reproduction Imperial College, London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Lewis","sequence":"additional","affiliation":[{"name":"National Phenome Centre Imperial College London  London UK"},{"name":"Section of Bioanalytical Chemistry Imperial College London  London UK"},{"name":"Department of Metabolism Digestion and Reproduction Imperial College, London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville","family":"DeSouza","sequence":"additional","affiliation":[{"name":"The Maudsley Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-3100","authenticated-orcid":false,"given":"Benjamin H","family":"Mullish","sequence":"additional","affiliation":[{"name":"Department of Metabolism Digestion and Reproduction Imperial College, London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Taylor","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"},{"name":"The Maudsley Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Ryan","sequence":"additional","affiliation":[{"name":"Imaging King's College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Whelan","sequence":"additional","affiliation":[{"name":"Nutritional Sciences King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies King's College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A. 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