NAME OF RESEARCHER
Chianna Umamahesan
NAME OF SUPERVISOR
Prof David Taylor, Dr R John Dobbs
PROJECT TITLE
Association of intestinal microbiome and metabolome with Parkinson’s disease: exploring role of immune-inflammatory mediators
CLINICAL ACADEMIC GROUP
Pharmaceutical Science
START & FINISH DATES
2017- April 2021
PROJECT DESCRIPTION
Viewing the gut as a strategic causal junctional point, we mapped potential drivers/mediators of idiopathic parkinsonism (IP). We characterised people with and without diagnosed IP: including dietary diaries; stool microbial metabolic products; intestinal inflammation; serum immune and inflammatory markers; and clinical manifestations of IP. Cluster analyses of metabolites discriminant for presence/absence of IP and clinical manifestations were performed.
What this research has shown.
Longer colon-transit was linked to lower concentrations of stool short-chain-fatty-acids (SCFAs) and a tryptophan containing cluster of metabolites. SCFAs are known to be essential to gut health and tryptophan to a healthy immune system. Cluster analysis of the IP manifestations aggregated prolonged colonic transit time with poverty and slowness of movement, tremor, sleep-disorder and smell disturbance, all being associated with lower ‘tryptophan-cluster’ concentrations. Rigidity was isolated in the manifestation-clustering and independent of metabolites in stool. Faster pulse was associated with lower concentrations in a metabolite-cluster containing anti-fungal and anti-inflammatory substances, and higher serum concentrations of an inflammatory marker which attracts white blood cells to the lining of the gut. Intestinal inflammation was greater in IP. Free-sugar intake was increased in IP, a higher intake being associated with intestinal inflammation. Lower caffeine, alcohol and water intakes (typical of IP) were associated with the lower concentrations of the cluster containing anti-fungal and anti-inflammatory substances.
Implications
IP may be a forme fruste of systemic-inflammatory-response, consequent on intestinal inflammation and faecal metabolome deficits.
PUBLICATIONS & CONFERENCES ATTENDED:
Umamahesan C, Augustin AD, Hayee BH, Ibrahim MAA, Taylor D, Weller C, Charlett A, Dobbs RJ, Dobbs SM. Intestinal inflammation and compromised barrier function in idiopathic parkinsonism: scenario captured by systematic review. Neuroimmunol Neuroinflammation 2021;8:313-28. http://dx.doi.org/10.20517/2347-8659.2020.57.
C. Umamahesan, A. Augustin, A. Le Guennec, D. Taylor, B.H. Hayee, M. Ibrahim, C. Weller1, A. Charlett, S. Dobbs, R.J. Dobbs. Clustering of deficient faecal metabolites aligns with clustering of clinical characteristics relevant to idiopathic parkinsonism. AD/PD conference 2022 Barcelona (oral presentation).