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