Session: Reviewing key ingredients shaping nutrition for healthy ageing Tuesday 22 nd 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
Log10 viable count 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. 12 10 8 * Children (1.5-7y) Adults (21-34 y) Elderly (67-88 y) 6 4 2 0 Total anaer Bifid Lacto Bacteroides Hopkins et al (2001) Gut 48: 198-205
Where you live determines your microbiota Unweighted UniFrac OTU PCoA Community Long-stay Young control Claesson et al. (2012) Nature 488, 178-184
Habitual diet differences in long-stay-like and healthy community dwellers Healthy Diet Less Healthy LS-Like Jeffery et al. (2016) ISME J 10(1):170-182
Genus Level Microbiota Healthy Diet Less Healthy LS-Like Intermediate LS-Like Intermediate Healthy Diet Jeffery et al. (2016) ISME J 10(1):170-182 unclassified Bacteroides Alistipes Parabacteroides Faecalibacterium Oscillospira Clostridium Coprococcus Ruminococcus Roseburia Lachnospira Blautia Eubacterium Prevotella Other
Definitions 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
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 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 Organism Before intake After intake P C. difficile Log 10 5.4 1.3 (31/42) Log 10 4.0 1.0 (8/31) <0.05 MRSA Log 10 8.0 (1/42) <Log 10 4.0 (0/31) Staphylococcus Log 10 5.7 1.0 (26/42) Log 10 4.6 0.6 (20/31) <0.01 Bian et al (2011) Int J Probiotics Prebiotics 6:123-132
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. Nagata S et al. (2016) Ann Nutr Metab. 68:51-9
Immunomodulatory Effects of Probiotics A randomised placebocontrolled, 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 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. Benton D et al. (2007) Eur J Clin Nutr. 61:355-61.
Effects of Probiotics on Depression: Age Related Huang R et al. (2016) Nutrients 8(8): 483.
Cognitive Function in Alzheimer s Disease 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 10 9 CFU/g for each) Result: the probiotic treated patients showed a significant improvement in the mini-mental state examination (MMSE) score 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
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. prebioticcontaining 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. 1 Macfarlane S et al 2006 Aliment Pharmacol Ther. 24: (5):701 714. 2 Schiffrin EJ et al 2007 J Nutr Heal Aging. 11: (6):475 479. 3 Bouhnik Y et al 2004 Am J Clin Nutr. 80: (6):1658 1664. 4 Kleessen B et al 1997 Am J Clin Nutr. 65: 1397 1402. 5 Fuller R & Gibson GR 1998. Clin Microbiol Infect 4: (2):477 480.
Is simply adding microbes enough? Are the microbes not there because conditions were unfavourable? Does the next generation of probiotics also need to consider optimising microbiome-host condition? Dietary intake, drugs, ingredients impacting ph, inflammation, bile salts Favourable conditions Supplementing missing microbes Probiotics (next generation) Therapeutic microbes Adding substrate Prebiotics (Personalised) diets
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