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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
http://apc.ucc.ie
http://eldermet.ucc.ie
October 31st 2013 PROBIO 2013: Probiotics BEYOND GUT HEALTH
Centre Mont-Royal Montréal (Québec) Canada
http://apc.ucc.ie/http://eldermet.ucc.ie/
The Globally Ageing Population
2000 -2030: adults worldwide >65 to double (420 million to 973 million)
Reference McGill (2010)
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
ELDERMET What did we do?
• Composition of faecal microbiota 500 subjects >65 years, T0, T3, T6
• 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
Elderly subjects – sampling
• Faeces
• Blood
• Urine
• Saliva
• Anthropometrics
• Food Diary FFQ
• MMT, FIT, Geriatric Depression
ELDERMET The gut microbiota of elderly is different to
that of younger adults
Claesson et al., 2011. PNAS USA.
Young-adult intestinal microbiota
Elderly adult intestinal microbiota
The Bacteroidetes : Firmicutes ratio varies considerably in elderly subjects
(14-91)% Bacteroidetes : (81-10%) Firmicutes
n = 160
Is variation in microbiota composition
related to community location, diet or
metadata?
• 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; 65-102 yrs.
Marcus Claesson Ian Jeffery
Probiotic Consumption
% o
f co
ho
rt
Microbiota separates by residence location
Community Long-stay Young control n = 191
Unweighted UniFrac OTU PCoA
Claesson et al., 2012. Nature.
Microbiota diversity correlates with diet diversity
What are the consequences for the host of microbiota differences?
Low diversity microbiota – different fecal water metabolome
Long-stay Community Rehab Community
Claesson et al., 2012. Nature.
Low diversity microbiota – lower gene count for SCFA production
• BCoAt: Butyryl-CoA transferase/Acetyl-CoA hydrolase • ACS: Acetate-formyltetrahydrofolate synthetase/Formate-tetrahydrofolate ligase • PCoAt: Propionyl-CoA:succinate-CoA transferase/Propionate CoA-transferase
No
rmal
ized
gen
e co
un
ts
Butyrate Propionate Acetate
Claesson et al., 2012. Nature.
Gradients in microbiota correlate with health measures
Claesson et al., 2012. Nature.
Low diversity microbiota - differential effect of antibiotic on Bifs
O’Sullivan et al., J. Antimicrob. Chemother. 2013; 68: 214–221.
O’Sullivan et al., J. Antimicrob. Chemother. 2013; 68: 214–221.
Low diversity microbiota – no differential reduction of lactobacilli
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., 2012. J. Clin. Microbiol.
108
106
104
102
0
0
Rea et al., 2011. Proc. Natl. Acad. Sci. 108:4639-4644.
T0
control
T24
Thuricin (90uM)
T24
control Van (90uM)
Met (90uM)
Phylum
Thuricin CD in faecal fermentations
Bacterial ecosystems as networks
Claesson et al., 2012. Nature 488: 178-184
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.
Probiotics improve diarrhoea in elderly
Hickson et al. 2007. BMJ
Average age = 74
Failure of probiotics to improve diarrhoea in residential care elderly
Allen et al. 2013. The Lancet 382: 1249
TMA metabolism, CVD, and the Archaebiotics concept
Brugere et al, Gut Microbes in press
Elderly are an at-risk group
– Immunosenescence
– Increased infection rates
– Reduced mucus production, barrier function, diverticulosis
– Increased transit time
Safety aspects of probiotic consumption
Sanders et al. Gut Microbes 2010
• Approximately a century of experience
• Lactobacillus infection estm. 1 per 107 in France
• Risk of lactobacillemia
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
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
Acknowledgements