Dr Mary Hickson - The role of probiotics in elderly care

The Role of Probiotics in

Elderly Care

Dr Mary Hickson

Imperial College Healthcare NHS Trust

Imperial College London

What are probiotics?

‘Live microorganisms which when

administered in adequate

amounts confer a health benefit

on the host’ (Food and Agriculture Organization of the

United Nations and World Health Organization

2001)

Examples of micro-organisms

investigated for probiotic effect • Lactobacillus rhamnosus GG

• Various Lactobacillus and Bifidobacterium strains

• Yeast: Saccharomyces boulardii

• Lactobacillus

• rhamnosus

• GG

http://www.customprobiotics.com/about_probiotics_continued.htm

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Gut microflora changes with

ageing

Consequences

Potential changes Consequence to health

SCFA formation risk of diarrhoea, Changes in

microflora, in faecal output

Proteolytic activity Toxic metabolites, risk of

Cancer

Breakdown of bile acids Toxic metabolites, risk of

Cancer

Alterations in colonisation

resistance

Resistance to disease, in

pathogenic bacteria

Changes to immunity within the

gut

risk of infection

Can we influence the gut

microflora to promote a more

beneficial mixture and thus,

produce health benefits?

Evidence • Gastrointestinal tract

– Diarrhoea

– Inflammatory bowel disease

– Helicobacter pylori infection

– Constipation

– Irritable bowel syndrome

• Other clinical conditions.

– Allergy

– Vaginosis

– Radiation enteritis

– Immunity

Hickson M (2013) Examining the evidence for the use of

probiotics in clinical practice. Nursing Standard. 27, 29, 35-

41.

AAD

Bacteroides

fragilis

Bacteroides

distasonis

Enterobacteriaceae

Clostridial rRNA

cluster IV

Clostridial rRNA

cluster XIVa

Bifidobacteria

VB Young & TM Schmidt. J Clin Microbiol.

2004 March; 42(3): 1203–1206

Antibiotic associated diarrhoea

Probiotics (Hempel 2012) Sys rev and meta analysis of 63

RCTs

Relative risk = 0.58 (95% CI, 0.50, 0.68; P < .001; I2, 54%)

Saccharomyces boulardii (Mcfarland 2010): Meta-analysis of

10 RCTs

Relative risk = 0.47 (95% CI: 0.35, 0.63 p<0.001)

L.rhamnosus GG (Mcfarland, 2007): Meta-analsysis of 6

RCTs

RR= 0.31 (95% CI: 0.13, 0.72, p=0.006)

C. difficile associated diarrhoea Goldenberg, 2013

Strain Number

of

studies

Number of

participants

Risk

Ratio

95%

confidence

intervals

All Species 22 4156 0.36 [0.26, 0.51]

L. acidophilus + L. casei (Bio K+) 3 781 0.21 [0.11, 0.42]

L. acidophilus + L.bulgaricus + B.

bifidum + S.thermophilus

1 100 0.28 [0.11, 0.67]

S. boulardii 7 1507 0.47 [0.24, 0.94]

L. casei + L. bulgaris +

S.thermophilus

1 109 0.05 [0.00, 0.84]

Lactobacillus GG 5 1131 0.63 [0.30, 1.33]

L. acidophilus + B.bifidum 1 138 0.40 [0.08, 1.99]

L. acidophilus 1 40 0.25 [0.01, 5.79]

Lactobacillus GG + L.acidophilus +

B. animalis

1 63 0.29 [0.01, 6.76]

VSL#3 - No cases of CDAD in trial 1 124 0.0 [0.0, 0.0]

L. plantarum 1 163 3.11 [0.13, 75.26]

Cost of Treatment

• No calculated costs for AAD

• Additional treatment costs for CDAD – £1835 (USA); £4000 (UK)

• Average cost of the probiotic= £10 per patient.

• The cost to prevent one case of: – AAD = £50

– CDAD = £60

Expert recommendations

• A: Prevention of antibiotic associated

diarrhoea in ambulatory and hospitalized

adult patients. LGG and S.boulardii shown

to be effective. L.casei, L bulgaricus and

S.Thermophilus drink also good evidence.

• B: Prevention of C.difficile associated

diarrhoea and its use in recurrent C.difficile

disease. Best data for LGG and S.boulardii

Floch MH et al. J.Clin.Gastroenterol.

2008, 42(supp 2) S104-S108

Constipation

• Bacteria influence gut motility

• Bifidobacteria in particular promote short

chain fatty acid production which

increases motility

• Decreased transit time

• Changes in stool consistency

• Changes in symptoms

• Reduction in laxative use

Transit time in the elderly

Meance et al. Microb Ecol Health Dis, 2003. 15: 15-22

Scand J Gastroenterol. 2011 September; 46(9): 1057–1064.

Published online 2011 June 13. doi: 10.3109/00365521.2011.584895

PMCID: PMC3171707

Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time

and functional gastrointestinal symptoms in adults

Randomised clinical trial: efficacy of Lactobacillus

paracasei‐enriched artichokes in the treatment of patients with

functional constipation – a double‐blind, controlled,

crossover study

Alimentary Pharmacology & Therapeutics Volume 35, Issue 4, pages 441-450, 8 JAN 2012 DOI: 10.1111/j.1365-2036.2011.04970.x http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04970.x/full#apt4970-fig-0003

J Nutr Health Aging. 2011 Mar;15(3):215-20.

Probiotics improve bowel movements in hospitalized elderly patients--the

PROAGE study.

Zaharoni H, Rimon E, Vardi H, Friger M, Bolotin A, Shahar DR

J Clin Gastroenterol. 2010 Sep;44 Suppl 1:S30-4.

doi:10.1097/MCG.0b013e3181ee31c3.

The use of probiotics in healthy volunteers with evacuation disorders and hard

stools: a double-blind, randomized, placebo-controlled study.

Del Piano M et al

• Improvement in symptoms:

– Number of Weekly Evacuations

– Consistency of Feces

– Ease of Expulsion

– Sensation of Complete Emptying

– Anal Itching, Burning, and Pain

– Abdominal Bloating

Recommendations

• “Insufficient evidence exists to conclude that

probiotics are effective for the management of

constipation.” (Canadian Association of

Gastroenterology)

• “Encouraging data that probiotics are helpful in

the treatment of IBS and constipation but that

additional research is needed.” (American

Society for Microbiology)

Immunity

In the over

75’s

infections

are a

major

cause of

death

Immune System

Innate and adaptive immunity

Mucosal immunity

V. Delcenserie et al.

Immunomodulatory

Effects of Probiotics in

the Intestinal Tract.

Curr. Issues Mol. Biol.

10: 37-54.

But: Does this make a difference to infection episodes?

Fukushima Y et al.

(2007) BJN, 98 (5)

969-977

de Vrese et al, Probiotic bacteria reduced duration and severity but not the

incidence of common cold episodes in a double blind, randomized, controlled

trial. Vaccine Volume 24, Issues 44–46 2006 6670 – 6674.

http://dx.doi.org/10.1016/j.vaccine.2006.05.048

No change in incidence

Recommendations

• A: The evidence has accumulated and

substantiated that the immune response is

definitely affected by the administration of

probiotics. (Floch MH et al. J.Clin.Gastroenterol.

2008, 42(supp 2) S104-S108)

Safety

“Current evidence suggests that the risk of

infection with probiotic lactobacilli or

bifidobacteria is similar to that of infection

with commensal strains, and that

consumption of such products presents a

negligible risk to consumers, including

immuno-compromised hosts.”

Borriello SP et al. Clin Infect

Dis 2003;36:775-80

Potential risk factors

• Immuno-compromised adults

• Neonates

• Presence of a central venous catheter

• Impaired intestinal barrier

• Post pyloric delivery of the probiotic

• Cardiac valve disease

Recommendations for clinical

practice

• Encouraging data

• Not robust or consistent enough

Qualities of an effective probiotic

dietary supplement:

1) Must be of human origin

2) Exert a beneficial effect on the host

3) Be non-pathogenic and non-toxic

4) Contain a large number of viable cells

5) Be capable of surviving and metabolizing

in the gut

6) Remain viable during storage and use

7) Be antagonistic to pathogens

Availability & quality of probiotic

products • Does it contain what it claims to?

• Are there other bacteria present?

• Do the bacteria survive gut transit?

• Do bacteria survive storage?

• What storage conditions are required?

• Ease of purchase and delivery

Will any probiotic do?

• NO

• Research relates to specific

strains

• Each strain must be shown to be

effective for a given problem with

a controlled trial

Quality of probiotic research

• Randomisation • Precise strain

• Blinding • Dose and Duration

• Power estimation • Method of administration

• Intention to treat analysis

and complete follow up

• Quality control of probiotic

• Patient group • Length of follow up

• Outcomes – clinically

relevant, functional

• Monitoring for Adverse events

Future studies

• Clinically relevant outcomes

• What population?

• What strain?

• What dose?

• What formulation?

• How does it work?

• Availability of quality product

Take home points

• Strain specific effects

• Good evidence for AAD

• Limited evidence for other conditions

• Use quality products