Session: Reviewing key ingredients shaping nutrition for healthy ageing Tuesday 22nd November 2016

Examining the effects of pre and probiotics on

gut microbiota during the ageing process

Louise R Wilson RD PhD Assistant Science Manager, Yakult UK Ltd

LWilson@yakult.co.uk www.yakult.co.uk/hcp

Outline

New insights into how the gut microbiota changes with age

• Changes in diet

• Place of residence

Applications for probiotics (and prebiotics) in the elderly

• Well researched applications: risks associated with antibiotic treatment, common infectious illnesses and gut-related problems in older people

• Emerging potential applications: immunomodulation, depression, cognitive function

In later life..

The composition of the gut microbiota changes to one that seems to be less healthy and less protective: microbial diversity declines, Bifidobacteria decrease and Enterobacteriaceae (Gram-negative bacteria) increases.

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2

4

6

8

10

12

Total anaer Bifid Lacto Bacteroides

Children (1.5-7y)

Adults (21-34 y)

Elderly (67-88 y)

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Hopkins et al (2001) Gut 48: 198-205

Community Long-stay Young control

Unweighted UniFrac OTU PCoA

Claesson et al. (2012) Nature 488, 178-184

Where you live determines your microbiota

Habitual diet differences in long-stay-like and healthy community dwellers

LS-Like

Less Healthy

Healthy Diet

Jeffery et al. (2016) ISME J 10(1):170-182

Healthy Diet

Intermediate Healthy Diet

Intermediate LS-Like unclassified

Bacteroides

Alistipes

Parabacteroides

Faecalibacterium

Oscillospira

Clostridium

Coprococcus

Ruminococcus

Roseburia

Lachnospira

Blautia

Eubacterium

Prevotella

Other

Less Healthy

LS-Like

Genus Level Microbiota

Jeffery et al. (2016) ISME J 10(1):170-182

Probiotic Live microorganisms that, when administered in adequate amounts confer a health benefit on the host Joint FAO/WHO (2002); Hill et al (2014)

Prebiotic A selectively fermented ingredient that allows specific changes, both in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Gibson GR et al (2010)

Synbiotic Probiotic + prebiotic

Definitions

Probiotic applications in the elderly

Applications in relevant risks associated with older age:

Antibiotic treatment (AAD & C diff)

Common infectious illness (norovirus, diarrhoea, fever, upper respiratory tract infections)

Common gut-related problems (bowel habits, constipation)

Emerging potential future applications:

Immunomodulation

Depression

Cognitive function

Effect of Probiotics on Microbiota, Bowel Habits & Illness (1)

Example of an LcS study in elderly care home patients Open-label study, n=42 elderly residential nursing home patients (82 y 10) Intervention: 6 months of probiotic (Lactobacillus casei Shirota) intake

Organism Before intake After intake P

C. difficile Log10 5.4 1.3 (31/42) Log10 4.0 1.0 (8/31) <0.05

MRSA Log10 8.0 (1/42) <Log10 4.0 (0/31)

Staphylococcus Log10 5.7 1.0 (26/42) Log10 4.6 0.6 (20/31) <0.01

Symptom Before intake After intake P

Fever (days per week) 1.36 2.18 0.95 1.58 <0.05

Constipation (times per week) 0.50 0.55 0.32 0.53 < 0.05

Diarrhoea (days per week) 0.31 0.52 0.16 0.44 <0.05

Bian et al (2011) Int J Probiotics Prebiotics 6:123-132

Nagata S et al. (2016) Ann Nutr Metab. 68:51-9

Effect of Probiotics on Microbiota, Bowel Habits & Illness (2)

Randomised placebo-controlled double-blind trial, n=72 elderly residents of facility for the elderly, aged 84-86 yrs

Intervention: 6 months of a probiotic (Lactobacillus casei Shirota) or placebo beverage

Nagata S et al. (2016) Ann Nutr Metab. 68:51-9

Effect of Probiotics on Microbiota, Bowel Habits & Illness (3)

In the probiotic group: Higher numbers of Bifidobacterium

and Lactobacillus Lower numbers of destructive

bacteria such as Clostridium difficile

Higher total acidity

Long-term consumption of LcS fermented milk may be useful for decreasing the daily risk of infection and improving the quality of life among the residents.

Immunomodulatory Effects of Probiotics

A randomised placebo-controlled, single-blind crossover study

4 wk intervention, 4 wk washout, 4 wk intervention

Probiotic intervention: Lactobacillus casei Shirota

n=30 healthy volunteers, aged 55-74 yrs

Consumption of probiotic drink improved NK cell activity in the elderly

Fig. 1 Effect of probiotic LcS consumption on NK cell activity. E/T = The ratios of effector/target cells

Dong et al (2013) Eur J Nutr 52(8): 1853-63

Probiotics Reported to Improve Mood/Ease Depression

Benton D et al. (2007) Eur J Clin Nutr. 61:355-61.

A double-blind placebo-controlled trial: 3-week intervention with either a probiotic (Lactobacillus casei Shirota) containing milk drink or a placebo

N=132 participants, mean age of 61.8 yrs

Consumption of probiotic-containing yoghurt improved the mood of those whose mood was initially poor.

Effects of Probiotics on Depression: Age Related

Huang R et al. (2016) Nutrients 8(8): 483.

Cognitive Function in Alzheimer’s Disease

Akbari E et al. (2016) Frontiers in Aging Neuroscience 10 Nov 2016. E-pub available ahead of print at http://journal.frontiersin.org/article/10.3389/fnagi.2016.00256/full

A 12-week RCT in 60 patients with Alzheimer’s disease (control vs probiotic, n=30 in each group)

Probiotic intervention: 200 ml/day probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 CFU/g for each)

Result: the probiotic treated patients showed a significant improvement in the mini-mental state examination (MMSE) score

Prebiotics

In prebiotic based studies, different combinations of prebiotics have been examined in elderly.

For example, use of inulin and its derivatives (FOS) has demonstrated an increment in abundance of Bifidobacteria, which led to reduction in markers of inflammation and increment in stool frequency. 1-5

However, eating foods that promote healthy species in the gut (eg. prebiotic-containing vegetables such as onions, leeks, asparagus, chicory and Jerusalem artichoke) can become difficult in old ager, particularly if there are dental problems or little appetite due to poor taste or smell.

1Macfarlane S et al 2006 Aliment Pharmacol Ther. 24: (5):701–714. 2Schiffrin EJ et al 2007 J Nutr Heal Aging. 11: (6):475–479. 3Bouhnik Y et al 2004 Am J Clin Nutr. 80: (6):1658–1664. 4Kleessen B et al 1997 Am J Clin Nutr. 65: 1397–1402. 5Fuller R & Gibson GR 1998. Clin Microbiol Infect 4: (2):477–480.

Is simply adding microbes enough?

Favourable conditions

Adding substrate Supplementing

missing microbes

Prebiotics (Personalised) diets

Probiotics (next generation) Therapeutic microbes

Dietary intake, drugs, ingredients impacting pH, inflammation, bile salts • Are the microbes not there because

conditions were unfavourable? • Does the next generation of

probiotics also need to consider optimising microbiome-host condition?

Thank you for listening!

Any questions?

Louise R Wilson RD PhD Assistant Science Manager, Yakult UK Ltd

LWilson@yakult.co.uk www.yakult.co.uk/hcp