Diet-microbiome-health interactions in older people Paul W. O Toole Prof. Microbial Genomics School of Microbiology, Univ. College Cork, Ireland APC Microbiome Institute, Univ. College Cork, Ireland http://apc.ucc.ie http://eldermet.ucc.ie December 4 th 2015 ILSI Europe Workshop 'The Gut Microbiome: Our Misunderstood Friend and Foe, Impact of the Gut Microbiome on Entero-hepatic Metabolism and Energy Availability' Brussels, Belgium, December 3-4 2015
ELDERMET Objectives Faecal microbiome 500 subjects >65 yrs, T 0, T 3, T 6 Clinical / health parameters Microbial metagenome & metabolome - test for correlations with health indices Stratification STRATUM Long stay 100 Rehab (<6 wks) 50 Day Hospital 50 Community 50 Community antibiotic 100 Clostridium difficile positive 100 Colon cancer 50 TOTAL 500 SUBJECTS
Microbiota separates by residence location Unweighted UniFrac OTU PCoA Community Long-stay Young control Claesson et al., 2012. Nature.
Procrustes: Microbiota & diet correlate, & by community location Unweighted UniFrac PCoA vs. FFQ PCA Community Long-stay
Separation of residence location by faecal water NMR metabolome Long-stay Community Rehab Community Dr. Martina Wallace and Dr. Lorraine Brennan, Univ. College Dublin
Integrating metabolome, metabolites & genus-level microbiota Co-inertia of microbiota & metabolome by location NMR spectrum metabolite PCA
Normalized gene counts Shotgun metagenome: differentially abundant SCFA genes 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., 2012. Nature.
Microbiota separation correlates with health measures Claesson et al., 2012. Nature.
Prof. Claudio Franceschi n = 1,250 UK, NL, FR, IT, PL T 0 12 mo. s 5 x 25 subjects
Fine detail analysis of diet-microbiota-health correlations n = 322 No antibiotics Novel clustering analysis applied
Microbiota-diet bi-clustering identifies intermediate and LS-like community subjects Long-stay Community
Mapping the microbiota in 3 dimensions identifies differential composition Long-stay Lack core Long-stay Core plus Long-stay type Community Core plus low abundance beneficial plus long-stay Unclustered Loss of structure Community Core plus beneficial Long stay Community Core only Jeffery, Lynch et al, ISME J 2015
Habitual diet differences in long-staylike and healthy community dwellers Healthy Diet Less Healthy LS-Like
Genus Level Microbiota Healthy Diet Less Healthy LS-Like Intermediate LS-Like Intermediate Healthy Diet unclassified Bacteroides Alistipes Parabacteroides Faecalibacterium Oscillospira Clostridium Coprococcus Ruminococcus Roseburia Lachnospira Blautia Eubacterium Prevotella Other
Microbiota composition changes with age O Toole & Jeffery, Science 2015
Microbiota and atherosclerosis http://apc.ucc.ie Diet (Fat, meat rich) L-carnitine PC Choline TMA H 2 Mx-methanogens have genes for dissimilating TMA Borrel et al 2012, 2013, 2014 Methanogens CH 4 TMAO Gut microbiota Brugere et al 2014, Gut Microbes Archaebiotics patent Liver FMO3 FMO3 TMAO Identified as an atherosclerosis trigger TMA Involved in trimethylaminuria
Dietary Ingredients Diet determines microbiota in 153 omnivores, vegans, vegetarians De Filipis et al 2015 Gut
Some Italian omnivores have high or medium compliance with Mediterranean diet De Filipis et al 2015 Gut
Dietary Ingredients Correlation between dietary ingredients and microbiota elements Microbiota De Filipis et al 2015 Gut
Diet and microbiota co-segregate by diet type or MD compliance level Dietary data Microbiota data
SCFA correlation to MD adherence ALL SUBJECTS OMNIVORES ONLY
Adherence to a Mediterranean diet lowers levels of TMAO, a bacterial metabolite linked to atherosclerosis De Filipis et al 2015 Gut
Diet-microbiota-health Summary Habitual diet correlates with microbiota; microbiota correlates with health Lower gene count in low diversity microbiota Fine-detail microbiota-diet clustering in community subjects confirms health correlations Correlations between TMA production genes, Mx levels, and faecal water methylamine levels Diet-microbiota-metabolome correlations in omnivores, vegans and vegetarians
Prof. Fergus Shanahan Dr. Syed (Akbar) Zulquernain Mr. Micheál O Riordáin Prof. Catherine Stanton Prof. Tony Ryan Prof. R. Paul Ross Prof. Colin Hill Dr. Denis O Mahony Prof. Gerald Fitzgerald Prof. Ted Dinan Dr. Julian Marchesi Dr. Anthony Fitzgerald Prof. Cillian Twomey Dr. Martina Wallace Dr. Lorraine Brennan Prof. Willy Molloy Dr. S. Timmons The Cork City Geriatricians Group Acknowledgements Ian Jeffery Denise Lynch Marcus Claesson Guillaume Borrel Huizi Tan Alexandra Ntemri Orla O Sullivan Mairead Coakley Mary Rea Fabien Cousin Jillian Browne Max Bourin Ludovica Butto Marta Neto Eimear Hurley Angela McCann Hugh Harris Eileen O Herlihy Patricia Egan J-F Brugere Danilo Ercolini