TY - JOUR
T1 - Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease
T2 - Integrative analysis indicates inflammatory response syndrome
AU - Augustin, Aisha
AU - Guennec, Adrien Le
AU - Umamahesan, Chianna
AU - Kendler-Rhodes, Aidan
AU - Tucker, Rosalind M
AU - Chekmeneva, Elena
AU - Takis, Panteleimon
AU - Lewis, Matthew
AU - Balasubramanian, Karthik
AU - DeSouza, Neville
AU - Mullish, Benjamin H
AU - Taylor, David
AU - Ryan, Suzanne
AU - Whelan, Kevin
AU - Ma, Yun
AU - Ibrahim, Mohammad A A
AU - Bjarnason, Ingvar
AU - Hayee, Bu' Hussain
AU - Charlett, André
AU - Dobbs, Sylvia M
AU - Dobbs, R John
AU - Weller, Clive
N1 - © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
U2 - 10.1002/ctm2.1152
DO - 10.1002/ctm2.1152
M3 - Article
C2 - 36588088
SN - 2001-1326
VL - 13
SP - e1152
JO - Clinical and Translational Medicine
JF - Clinical and Translational Medicine
IS - 1
ER -