Gut microbiota and health in elderly subjects a role for probiotics? Paul W. O Toole
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1 Gut microbiota and health in elderly subjects a role for probiotics? Paul W. O Toole School of Microbiology, Univ. College Cork, Ireland Alimentary Pharmabiotic Centre, Univ. College Cork, Ireland October 31 st 2013 PROBIO 2013: Probiotics BEYOND GUT HEALTH Centre Mont-Royal Montréal (Québec) Canada
2 The Globally Ageing Population : adults worldwide >65 to double (420 million to 973 million) Reference McGill (2010)
3 Why older persons? Changes in microbiota composition and activity Increased infection rates Increased inflammatory disease Prospects for dietary intervention/modulation Reviewed in Guigoz et al., 2008 Curr. Op. Clin. Nutr. Metab. Care 11:13-20
4 ELDERMET What did we do? Composition of faecal microbiota 500 subjects >65 years, T 0, T 3, T 6 Measure specific clinical/health parameters Microbial metagenome & metabolome of selected individuals, test for correlations with health indices Stratification STRATUM SUBJECTS Long stay 100 Rehab 50 Day Hospital 50 Community 50 Community antibiotic 100 Clostridium difficile positive 100 Colon cancer 50 TOTAL 500
5 Elderly subjects sampling Faeces Blood Urine Saliva Anthropometrics Food Diary FFQ MMT, FIT, Geriatric Depression
6 ELDERMET The gut microbiota of elderly is different to that of younger adults Young-adult intestinal microbiota Elderly adult intestinal microbiota Claesson et al., PNAS USA.
7 The Bacteroidetes : Firmicutes ratio varies considerably in elderly subjects n = 160 (14-91)% Bacteroidetes : (81-10%) Firmicutes
8 Is variation in microbiota composition related to community location, diet or metadata? Marcus Claesson 83 Community-dwelling 20 Day hospital (out-patient) 15 Rehabilitation ( 6 weeks) 60 Long-stay (>6 weeks) (13 Young healthy controls) 191 Mean age 78+/- 8; yrs. Ian Jeffery
9 % of cohort Probiotic Consumption
10 Microbiota separates by residence location Unweighted UniFrac OTU PCoA Community Long-stay Young control n = 191 Claesson et al., Nature.
11 Microbiota diversity correlates with diet diversity
12 What are the consequences for the host of microbiota differences?
13 Low diversity microbiota different fecal water metabolome Long-stay Community Rehab Community Claesson et al., Nature.
14 Normalized gene counts Low diversity microbiota lower gene count for SCFA production 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.
15 Gradients in microbiota correlate with health measures Claesson et al., Nature.
16 Low diversity microbiota - differential effect of antibiotic on Bifs O Sullivan et al., J. Antimicrob. Chemother. 2013; 68:
17 Low diversity microbiota no differential reduction of lactobacilli O Sullivan et al., J. Antimicrob. Chemother. 2013; 68:
18 C. difficile status as a function of microbiota Carriage rate 1.6% (n = 123) community 9.5% (n = 43) out-patients 21% (n = 151) short- or long-term care in hospital. Dominant 072 ribotype - 43% of Cd+ subjects Hypervirulent strain R027-3 subjects (11%), Reduced microbiota diversity in CDAD R027+ subjects. Rea et al., J. Clin. Microbiol.
19 Thuricin CD in faecal fermentations Phylum 10 8 T 0 T 24 T control Van (90uM) Met (90uM) control Thuricin (90uM) Rea et al., Proc. Natl. Acad. Sci. 108:
20 Bacterial ecosystems as networks Claesson et al., Nature 488:
21 Could probiotics improve health by modulating the intestinal microbiota? Good evidence that probiotics increase abundance of related organisms e.g. Weak evidence that probiotics re-shape overall microbiota e.g.
22 Probiotics improve diarrhoea in elderly Average age = 74 Hickson et al BMJ
23 Failure of probiotics to improve diarrhoea in residential care elderly Allen et al The Lancet 382: 1249
24 TMA metabolism, CVD, and the Archaebiotics concept Brugere et al, Gut Microbes in press
25 Elderly are an at-risk group Immunosenescence Increased infection rates Reduced mucus production, barrier function, diverticulosis Increased transit time
26 Safety aspects of probiotic consumption Approximately a century of experience Lactobacillus infection estm. 1 per 10 7 in France Risk of lactobacillemia <1/10 6 No increase in Finland with L. rhamnosus GG Impressive safety record in immunocompromised patients (eg. HIV, premature infants, elderly, IBD) Low (not zero) opportunistic pathogenicity Sanders et al. Gut Microbes 2010
27 Conclusions Probiotics may benefit elderly subjects for similar reasons as general population Latest microbiota profiling indicates depletions, anomalies and enrichments that represent targets for new probiotics Accepted exclusion criteria should be rigorously applied
28 Acknowledgements Prof. Fergus Shanahan Prof. R. Paul Ross Dr. Denis O Mahony Dr. Catherine Stanton Prof. Gerald Fitzgerald Prof. Ted Dinan Dr. Julian Marchesi Prof. Colin Hill Dr. Douwe van Sinderen Dr. Anthony Fitzgerald Prof. Cillian Twomey Prof. Eamonn Quigley Dr. Suzanne Timmons Prof. Willie Molloy Dr. Jean-Francois Brugere Dr. Marcus Claesson Dr. Ian Jeffery Dr. Guillaume Borrel Dr. Siobhán Cusack Dr. Eibhlis O Connor Dr. Eileen O Herlihy Ms. Karen O Donovan RN Ms. Patricia Egan RN Dr. Orla O Sullivan Ms. Jennifer Deane B. Sc. Ms. Mairead Coakley M. Sc. Ms. Bhuna Laks M. Sc. Dr. Susana Conde Mr. Hugh Harris M.Sc. Dr. J. Brown Dr. M. Fraher Dr. Mary Rea Ms. Susan Power B.Sc. Plus The Cork City Geriatricians Group
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