Diet-Microbiota Interactions and The Elderly
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1 DEPARTMENT OF AGTTC GATCGATTTGTC G ACCCAG C T A AGGATAGAGTGAT GA UNIVERSITY COLLEGE CORK Diet-Microbiota Interactions and The Elderly Ian Jeffery Dept. Microbiology, Univ. College Cork, Ireland Alimentary Pharmabiotic Centre, Univ. College Cork, Ireland
2 The human gut microbiota ~10 times more bacterial cells in GIT than human cells in body ~ 150 times more bacterial genes than human genes Perform a number of beneficial functions Variations in the gut microbiota in disease
3 Diseases with microbiota linkages Irritable Bowel Syndrome Obesity
4 Why elderly? Gut microbiota as an indicator and agent for nutritional health in elderly Irish subjects Increasing proportion in population Increased susceptibility to infection Increased inflammatory status (Inflamm-aging) Changes in microbiota composition and activity Prospect of dietary modulation
5 Data: 178 elderly ( 65yrs) Irish subjects 83 Community-dwelling 20 Day hospital (out-patient) 15 Rehabilitation ( 6 weeks) 60 Long-stay (>6 weeks) (13 Young healthy controls) Eldermet dataset Metabolomics (NMR) 16S rdna amplicons (454) & shotgun (Illumina) sequencing Clinical Variables BMI, frailty malnourishment, depression cognitive function dementia No antibiotics treatment 1 month prior sampling Dietary data 168 elderly subjects food frequency questionnaire (FFQ), 147-item, weighted by 10 consumption frequencies.
6 Subjects separate by community location 5.4 million 16S rdna reads => 47,500 OTUs Unweighted UniFrac OTU PCoA Community Long-stay Young control
7 Subjects separated by community location Unweighted UniFrac OTU PCoA Hierarchical Ward-linkage clustering based on Spearman correlation coefficients of the proportion of OTUs for each subject
8 What impact has diet on microbiota? Food Frequency Questionnaire (FFQ) Long-term dietary habits FFQ data for 96% elderly subjects 147 food types (beef/apples/white rice/potatoes/milk/porridge etc) Healthy Food Diversity (HFD): how diverse AND healthy a diet is
9 FFQ multivariate analysis Complete-linkage clustering based on Euclidean distances to PC1 Driving food types FFQ CoA Correspondence analysis DG1: low fat / high fibre DG2: moderate fat and fibre DG3: moderate fat / low fibre DG4: high fat / moderate fibre
10 Microbiota & diet by community location Unweighted UniFrac PCoA vs. FFQ PCA Weighted UniFrac PCoA vs. FFQ PCA Diet Community Microbiota Long-stay
11 Microbiota & diet by duration in long-stay care N/A (C+DH) Diet Week0to6 (Rehab) Microbiota Week6toYear1 Year1+
12 Diversity of microbiota and diet Healthy Food Diversity index (HFD) showed that it positively correlated with microbial diversity indices Significant differences across the four groups, suggest that a healthy diverse diet promotes a more diverse gut microbiota.
13 Separation of residence location by faecal water NMR metabolome Long-stay Community Rehab Community Dr. Martina Wallace and Dr. Lorraine Brennan, Univ. College Dublin
14 Integrating metabolome, metabolites & genus-level microbiota Co-inertia of microbiota & metabolome by location NMR spectrum metabolite PCA
15 Shotgun metagenome: differentially abundant SCFA genes Normalized gene counts Butyrate Acetate Propionate BCoAt: Butyryl-CoA transferase/acetyl-coa hydrolase ACS: Acetate-formyltetrahydrofolate synthetase/formate-tetrahydrofolate ligase PCoAt: Propionyl-CoA:succinate-CoA transferase/propionate CoA-transferase Claesson et al., Nature.
16 Microbiota-health correlations Health/clinical markers BMI: Body Mass Index CC: Calf Circumference MAC: Mid-Arm Circumference SBP: Systolic Blood Pressure DBP: Diastolic Blood Pressure CCI: Charlson Index of Comorbidity Barthel Index of Activities of Daily Living FIM: Functional Independence Measure MMSE: Mini-Mental State Exam MNA: Mini-Nutritional Assessment Possible confounders Antibiotics: Exclude <1mo >1mo had no sign. effect on µ-biota (α- or ß-diversity) Quantile regression model adjusted for: Age Gender Location Medication
17 Microbiota separation correlates with health measures Location-specific unweighted UniFrac PCoAs Community-only subjects All four location subjects Community Long-stay Long-stay-only subjects Following adjustment for age/gender/location/medication, microbiota correlates significantly with e.g. frailty and inflammation. Prospective studies needed to establish causality.
18 Microbiota separation correlates with health measures Location-specific unweighted UniFrac PCoAs Community-only subjects All four location subjects Community Long-stay Long-stay-only subjects Following adjustment for age/gender/location/medication, microbiota correlates significantly with e.g. frailty and inflammation. Prospective studies needed to establish causality.
19 Microbiota clustering correlates with health measures Unweighted UniFrac OTU PCoA
20 Microbiota clustering correlates with health measures Unweighted UniFrac OTU PCoA
21 Microbiota clustering correlates with health measures Unweighted UniFrac OTU PCoA
22 Summary (Claesson, Jeffery et al., 2012 Nature) Microbiota in elderly is different depending on community location Driven by habitual diet Microbiota alterations correlate with health changes especially in long-stay Diet shapes gut microbiota, which may impact on health in elderly people May lead to carefully designed dietary interventions to promote healthier aging
23 n = 1,250 UK, NL, FR, IT, PL T 0 12 mo. s 5 x 25 subjects
24 Challenges Microbiota modulation / restoration Prospective / longitudinal studies Interventions Intergrated metabolomics, nutritional and microbial datasets Dietary guidelines informed by microbiota needs
25 Acknowledgements Paul O Toole Anthony Fitzgerald Denis O Mahony Paul Ross Catherine Stanton Gerald Fitzgerald Fergus Shanahan Ted Dinan Martina Wallace Julian Marchesi Lorraine Brennan Michael O Connor Douwe van Sinderen Colin Hill Cillian Twomey Kieran O Connor Lorraine Brennan Denise Lynch Eileen O'Herlihy Marcus Claesson Eibhlis O Connor Siobhán Cusack Hugh Harris Susana Conde Jennifer Deane Orla O Sullivan Mary Rea Colm Henry Mairead Coakley Patricia Egan Susan Power Karen O Donovan Ann O Neill Norma Harnedy Bhuna Laks Martina Wallace The Cork City Geriatricians Group
26
27 Microbiota clustering correlates with health measures Unweighted UniFrac OTU PCoA
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