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