Diet-microbiome-health interactions in older people

Transcription

1 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 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

2 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

3 Microbiota separates by residence location Unweighted UniFrac OTU PCoA Community Long-stay Young control Claesson et al., Nature.

4 Procrustes: Microbiota & diet correlate, & by community location Unweighted UniFrac PCoA vs. FFQ PCA Community Long-stay

5 Separation of residence location by faecal water NMR metabolome Long-stay Community Rehab Community Dr. Martina Wallace and Dr. Lorraine Brennan, Univ. College Dublin

6 Integrating metabolome, metabolites & genus-level microbiota Co-inertia of microbiota & metabolome by location NMR spectrum metabolite PCA

7 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., Nature.

8 Microbiota separation correlates with health measures Claesson et al., Nature.

9 Prof. Claudio Franceschi n = 1,250 UK, NL, FR, IT, PL T 0 12 mo. s 5 x 25 subjects

10 Fine detail analysis of diet-microbiota-health correlations n = 322 No antibiotics Novel clustering analysis applied

11 Microbiota-diet bi-clustering identifies intermediate and LS-like community subjects Long-stay Community

12 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

13 Habitual diet differences in long-staylike and healthy community dwellers Healthy Diet Less Healthy LS-Like

14 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

15 Microbiota composition changes with age O Toole & Jeffery, Science 2015

16 Microbiota and atherosclerosis 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

17 Dietary Ingredients Diet determines microbiota in 153 omnivores, vegans, vegetarians De Filipis et al 2015 Gut

18 Some Italian omnivores have high or medium compliance with Mediterranean diet De Filipis et al 2015 Gut

19 Dietary Ingredients Correlation between dietary ingredients and microbiota elements Microbiota De Filipis et al 2015 Gut

20 Diet and microbiota co-segregate by diet type or MD compliance level Dietary data Microbiota data

21 SCFA correlation to MD adherence ALL SUBJECTS OMNIVORES ONLY

22 Adherence to a Mediterranean diet lowers levels of TMAO, a bacterial metabolite linked to atherosclerosis De Filipis et al 2015 Gut

23 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

24 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