Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

Autor: Augustin A; Institute of Pharmaceutical Science, King's College London, London, UK.; The Maudsley Hospital, London, UK., Guennec AL; NMR Facility, King's College London, London, UK., Umamahesan C; Institute of Pharmaceutical Science, King's College London, London, UK.; The Maudsley Hospital, London, UK., Kendler-Rhodes A; Nutritional Sciences, King's College London, London, UK., Tucker RM; Institute of Pharmaceutical Science, King's College London, London, UK.; The Maudsley Hospital, London, UK., Chekmeneva E; National Phenome Centre, Imperial College London, London, UK.; Section of Bioanalytical Chemistry, Imperial College London, London, UK.; Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK., Takis P; National Phenome Centre, Imperial College London, London, UK.; Section of Bioanalytical Chemistry, Imperial College London, London, UK.; Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK., Lewis M; National Phenome Centre, Imperial College London, London, UK.; Section of Bioanalytical Chemistry, Imperial College London, London, UK.; Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK., Balasubramanian K; Institute of Pharmaceutical Science, King's College London, London, UK., DeSouza N; The Maudsley Hospital, London, UK., Mullish BH; Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK., Taylor D; Institute of Pharmaceutical Science, King's College London, London, UK.; The Maudsley Hospital, London, UK., Ryan S; Imaging, King's College Hospital, London, UK., Whelan K; Nutritional Sciences, King's College London, London, UK., Ma Y; Institute of Liver Studies, King's College Hospital, London, UK., Ibrahim MAA; Immunological Medicine, King's College Hospital, London, UK., Bjarnason I; Gastroenterology, King's College Hospital, London, UK., Hayee BH; Gastroenterology, King's College Hospital, London, UK., Charlett A; Institute of Pharmaceutical Science, King's College London, London, UK.; Statistics, Modelling and Economics, UK Health Security Agency, London, UK., Dobbs SM; Institute of Pharmaceutical Science, King's College London, London, UK.; Gastroenterology, King's College Hospital, London, UK., Dobbs RJ; Institute of Pharmaceutical Science, King's College London, London, UK.; Gastroenterology, King's College Hospital, London, UK., Weller C; Institute of Pharmaceutical Science, King's College London, London, UK.
Jazyk: angličtina
Zdroj: Clinical and translational medicine [Clin Transl Med] 2023 Jan; Vol. 13 (1), pp. e1152.
DOI: 10.1002/ctm2.1152
Abstrakt: Background: Gut-brain 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-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide.
Methods: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed.
Results: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) 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-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point.
Conclusions: 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 syndrome.
(© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
Databáze: MEDLINE
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