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Volume 7.17 - 19th October 2017

THE GUT MICROBIOTA IN OLDER ADULTS AND THE POTENTIAL FOR PROBIOTICS Victoria Avery ANutr Science Officer, Yakult UK Ltd Victoria has an MSc in Nutrition from the University of Surrey. She is currently an Associate Nutritionist, working towards becoming a Registered Nutritionist

Dr Louise Wilson RD Assistant Science Manager, Yakult UK Ltd Louise is a Registered Dietitian with over seven yearsâ&#x20AC;&#x2122; experience of scientific research and writing publications in the field of nutrition and health.

Not only is the UK population at its largest, but it is also at its oldest. The latest data from the National Office for Statistics has shown that in 2016, 18% of the population were over the age of 65 years and 2.5% were over the age of 85 years.1 Reducing the level of ill health and thus increasing healthy life expectancy is therefore more relevant than ever before, and would not only be of benefit to an individual through an improvement in their quality of life, but it would also reduce expenditure on public resources including those of the NHS. The potential for the gut microbiota to affect health is particularly relevant for older adults, defined as those aged 65 years and over, as the microbiota has been shown to be associated with agerelated changes in innate immunity, sarcopenia and cognitive function, all of which are elements of frailty. Over the last decade our knowledge of how the gut microbiota changes with age has broadened and we now have a far greater understanding of key factors driving these changes and the implications for health, and we are beginning to develop an idea of what we might be able to do to optimise healthy aging of the gut microbiota. MICROBIOTA COMPOSITION

Extensive research has explored how the human intestine is colonised immediately after birth, and how the gut microbiota changes within the first two years of life before becoming

relatively stable and remaining so throughout adulthood.2 However, more recent evidence has shown that changes in the gut microbiota also occur in older adults which may have an impact on health.3 This will be explored and discussed further in this article. A number of variations in the composition of the gut microbiota in older adults, compared to younger adults, has been reported. Typically, the gut microbiota changes to one that seems to be less healthy and less protective. For several years, research using bacterial isolation techniques has shown that microbial diversity tends to be lower in older adults when compared to younger adults and that numbers and diversity of bifidobacteria decrease.4-5 However, as discussed in a thorough review in 2012, recent studies based on current molecular techniques have not consistently confirmed these findings.6

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NHD CPD eArticle Low diversity in the gut microbiota has been found to be associated with increased health risks, and the specific loss of diversity within core microbiota groups has been associated with increased frailty and reduced cognitive function.8 There is also a general consensus of opinion that the age-related changes of the gut microbiota alter the gut environment to make it more favourable for growth of pathogens, with an increased associated disease risk for the elderly.9 At this stage, it remains unclear as to whether the common changes in microbiota that are seen in older adults are correlative or causative of health loss seen with aging, however there are several national and international studies, such as the EU-funded NuAge project,10 that are allowing us to begin to better understand this relationship. The ELDERMET study is a project based in Ireland, contributing to the NuAge project, that aims to assess the faecal microbiota composition of elderly volunteers in the Irish population, explore potential correlations between this and a range of health indices, develop specific dietary recommendations to improve the health of the elderly consumer and finally to provide evidence-based recommendations for prospective studies to determine the molecular mechanisms for health improvements promoted by specific food ingredients that modulate components of the microbiota.11 This research project has provided some of the key insights of recent years in this field. In an initial analysis of 161 elderly subjects (>65 years), the team of researchers identified considerable inter-individual variability in faecal microbiota composition.5 In another analysis of 178 elderly subjects, the researchers investigated the link between diet, environment, health and gut microbiota to see if these factors could explain the inter-individual variability previously identified.12 The research team included subjects who were community-dwelling (living at home), community-dwelling but attending out-patient day hospitals, in short-term rehab

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hospital care for up to 6 weeks, or in long-term residential care. Interestingly the researchers found that microbiota composition correlated with residential setting: people living in their own homes and those attending occasional day hospitals had a diverse gut microbial profile which was close to that found in healthy younger adults, whereas those living in long-term residential care, and even those in short-term hospital care, had a very different gut microbiota with a low diversity. These data suggested that the environment within which someone is living is a determinant of gut microbiota. However, further analysis that factored in dietary intake identified the same clustering patterns: when the subjects were grouped based on dietary intakes these groups also reflected the individuals residential setting. Those consuming the poorest quality diets (high fat and low fibre) were also those living in long-term residential care or in short-term hospital care as opposed to their own homes, and these were also the subjects with the lowest gut microbial diversity. Furthermore, those who did live at home but consumed a diet that was similar to that of long-stay resident’s diets (high fat and low fibre), defined as a ‘long-stay like diet’, actually had a microbial diversity similar to that of the long-stay residential care individuals rather than other communitydwelling individuals. In further analysis13 of faecal samples taken from 384 subjects, including 13 younger controls, at 3-monthly intervals, the duration of time within a long-stay residential setting was associated with the loss of microbial diversity. This data highlights that dietary intakes remain a key determinant of the gut microbiota in older age, and a healthy, varied diet supports maintenance of diverse gut microbiota. As well as dietary intakes, the multiple medications that an older adult might be on may also be a determinant of the composition of the gut microbiota.14 Of particular importance to consider are antibiotics, as they are known to

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WHAT TO LOOK FOR IN A PROBIOTIC A guide for healthcare professionals CHECK THE LABEL AND QUALITY

Does the label state the full strain name of the microorganism(s) in the product?

Does the label state the number of live cells of the probiotic strain(s) in the product?

NOTE: This should comprise three components: genus, species and strain identiﬁer.

Yakult contains 1010 Lactobacillus casei Shirota per 100 ml, when refrigerated.

Genus (e.g. Lactobacillus), species (e.g. casei) and strain (e.g. Shirota) is stated in full on Yakult’s packaging.

This is equivalent to 6.5 billion live cells per 65ml bottle.

Contact the company. Are there quality control procedures in place? NOTE: This is necessary to ensure the product contains the correct strains and number of live microbial cells as stated on the label.

Yakult is acknowledged by experts to be a quality probiotic.

CHECK THE SCIENTIFIC EVIDENCE

Contact the company or access their HCP website, to ﬁnd the supporting research. NOTE: (i) Regulatory restrictions mean companies can share research information with HCPs but not the general public; (ii) Not all probiotic research papers can be found on medical literature databases.

The research evidence for Lactobacillus casei Shirota can be found at www.yakult.co.uk/hcp or by contacting science@yakult.co.uk

CHECK FOR GI TRACT SURVIVAL

CHECK FOR EFFICACY OF THE STRAIN

For oral probiotics, are there human intervention trials showing survival of the probiotic strain(s) through the gut?

Check for trials and studies for the probiotic and the particular patient problem

NOTE : In vitro or model studies are not proof of gut survival in vivo.

(important for assessment of safety).

There are several research papers describing human studies showing the gut survival of Lactobacillus casei Shirota.

See expert advice in ‘LcS Insight: HCP Study Day 2014’ and ‘Your Guide to Probiotics’.

For further support on what to look for in a probiotic or to access the research behind Yakult, then please visit www.yakult.co.uk/hcp contact science@yakult.co.uk or call 020 8842 7600 This resource is intended for healthcare professionals. Not to be distributed to patients.

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The decline in physiological and immunological functions that occurs in later life is an underlying reason for various health issues faced by older adults. have a major effect on gut bacteria, killing off large numbers including those linked to health. Interestingly, the impact of taking antibiotics has been shown to be greater in community dwelling subjects as they showed a greater loss in diversity when compared to those taking antibiotics in long-term residential care.13 However, the community-dwelling subjects also showed greater recovery of the microbial profile following antibiotic treatment. An individualâ&#x20AC;&#x2122;s microbial profile prior to taking antibiotics is therefore an important factor when considering how the gut microbiota may change in response to antibiotics. PROBIOTIC POTENTIAL

The decline in physiological and immunological functions that occurs in later life is an underlying reason for various health issues faced by older adults. Common problems include gut disorders and increased susceptibility to infections such as colds, urinary tract infections and nosocomial infections such as Clostridium difficile and methicillin resistant Staphylococcus aureus (MRSA).15 Knowledge of the link between the gut microbiota and health has prompted research into how probiotics may help maintain health in older adults, especially in those within long-term residential care settings who are likely to have a less diverse microbiota. There have been several research studies conducted in elderly care homes, with a range of positive effects being reported including modulation of the gut microbiota profile. In a study investigating the effects of a widely available probiotic, Lactobacillus casei Shirota (LcS), on gut disorders and susceptibility to infections among care homes,16 seventy-two residents at an elderly care facility in Japan were

randomised to receive either the probiotic (n=36) or a placebo (n=36) once daily for six months. At the end of the six-month intervention, the elderly residents consuming the probiotic had significantly fewer episodes of constipation and had significantly fewer days on average with a fever, when compared to the placebo group. Faecal analysis also showed an apparently improved microbial profile in the probiotic group: Bifidobacterium and Lactobacilli numbers were significantly higher than at baseline, and numbers of potentially harmful bacteria such as C. difficile, C. perfringens and Enterobacteriaceae were lower in the probiotic group compared to the placebo group throughout the intervention period. This study demonstrates that intervention with LcS can results in a number of positive effects that will help to maintain the health of the residents. The effect of the probiotic LcS on bowel function has also been investigated in a Dutch nursing home,17 where nursing staff recorded the number of bowel movements and consistency of stools of forty-four residents aged 74 to 99 years of age. Data from the period three weeks before the probiotic intervention were compared with data from the six-week period of probiotic intervention. The probiotic was associated with improved bowel habits as seen by an increase in the percentage of ideal stool types per week, and a decrease in constipation-type stools and diarrhoea-type stools. As previously highlighted, antibiotics can lead to a loss of microbiota in older adults and subsequently this leads to a reduced resistance to pathogens such as Clostridium difficile (C. diff). Although C. diff can reside in the gut without causing any problems, when the protective commensal gut microbiota is disturbed by

NHD CPD eArticle antibiotics it can grow and produce toxins. As C. diff has been detected in up to 51% of older adults in long-term care facilities,18 the use of probiotics in the prevention of C. diff associated diarrhoea (CDAD) has been studied across a variety of probiotic strains and doses. A 2013 Cochrane review of 23 randomised controlled trials, including trials in older adults, concluded that there is moderate quality evidence that probiotics are effective for prevention CDAD in both children and adults.19 There is an ongoing trial in the UK, called the PRINCESS trial,20 that is currently investigating whether the widely available probiotic containing Lactobacillus rhamnosus and Bifidobacterium animalis is effective in reducing the number of infections in care home residents and subsequently reducing antibiotic administration in this group. This trial is not due

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to end until 2019, and so it is likely that results won’t be available until 2019/20, but if positive it will support the accumulating data to suggest the use of probiotics in care homes may not only improve health outcomes but also save money. CONCLUSIONS

There seems to be an ever-increasing body of evidence to suggest that older adults are a group who would particularly benefit from a daily probiotic, particularly those whose dietary intake has limited variety which subsequently leads to a less diverse gut microbiota profile. It is important to bear in mind that evidence for probiotics efficacy is considered strainspecific, therefore dietitians and other healthcare professionals are advised to check the supporting research for any probiotic they are considering using or recommending.

Further reading: A general guide to probiotics has been published by the British Journal of Nursing21 and a handy flowchart resource reminding healthcare professionals of what to look for in a probiotic (including quality, safety and efficacy) has been produced by the science team at Yakult UK.22 References 1. Office for National Statistics (2017) Overview of the UK Population: July 2017, www.ons.gov.uk Available at https://www.ons.gov.uk/ peoplepopulationandcommunity/populationandmigration/populationestimates/articles/overviewoftheukpopulation/july2017 2. Zoetendal EG, Akkermans AD & De Vos WM (1998) Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl Environ Microbiol 64: 3854–3859 3. O’Toole PW & Claesson MJ (2010) Gut microbiota: changes throughout the lifespan from infancy to elderly. Int Dairy J 20(4): 281-291. 4. Duncan SH & Flint HJ (2013) Probiotics and prebiotics and health in ageing populations. Maturitas 75(1): 44-50. 5. Claesson MJ, Cusack S, O’Sullivan O et al. (2011). Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci 108(1): 4586-4591. 6. Biagi E, Candela M, Fairweather-Tait S et al. (2012) Ageing of the human metaorganism: the microbial counterpart. Age 34(1): 247-267. 7. Shoaie S, Ghaffari P, Kovatcheva-Datchary P et al. (2015) Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab 22(2):320-31. 8. O’Toole PW & Jeffrey IB (2015) Gut microbiota and aging. Science 350(6265): 1214-1215. 9. Hopkins MJ & Macfarlane GT (2002) Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol 51(5): 448-54. 10. Santoro A, Pini E et al. (2014) Combating inflammaging through a Mediterranean whole diet approach: the NU-AGE project’s conceptual framework and design. Mech Ageing Dev 136: 3-13. 11. http://eldermet.ucc.ie/ 12. Claesson MJ, Jeffery IB, Conde S et al. (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 492(7427): 178-185. 13. Jeffery IB, Lynch DB & O’Toole PW. (2016) Composition and temporal stability of the gut microbiota in older persons. The ISME Journal 10: 170-182. 14. Ticinesi A, Milani C, Lauretani F et al. (2017) Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Scientific Reports 7: 11102 15. Gerba CP, Rose JB & Haas CN (1996) Sensitive populations: who is at the greatest risk? Int J Food Micobiol 30:113-123. 16. Nagata S, Asahara T, Wang C et al. (2016) The effectiveness of Lactobacillus beverages in controlling infections among the residents of an aged care facility: a randomized placebo-controlled double-blind trial. Annals Nutr Metab 68(1): 51-9. 17. Van den Nieuwboer M, Klomp-Hogeterp A, Verdoorn S et al. (2015) Improving the bowel habits of elderly residents in a nursing home using probiotic fermented milk. Beneficial Microbes 6(4): 397-403. 18. Furuya-Kanamori L, Marquess J, Yakob L et al. (2015) BMC Infect Dis 15: 516 19. Goldenberg JZ, Ma SS, Saxton JD et al. (2013), Martzen MR, Vandvik PO, Thorlund K, Guyatt GH, Johnston BC. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 5:CD006095 20. Current Controlled trials [Internet]. London: BioMed Central - ISRCTN 16392920, Probiotics to reduce infections in care home residents: 2016 July 14. Available from http://www.isrctn.com/ISRCTN16392920 21. Thomas LV & Whelan K (2013) Your Guide to Probiotics. Published by British Journal of Nursing and Gastrointestinal Nursing. [Reprints available from science@yakult.co.uk] 22. Yakult UK. What to Look For in a Probiotic: A Guide for Healthcare Professionals. 2016. [Reprints available from science@yakult.co.uk] Copyright © 2017 NH Publishing Ltd - All rights reserved. Available for printing and sharing for the use of CPD activities for personal use. Not for reproduction for publishing purposes without written permission from NH Publishing Ltd.

NHD CPD eArticle NETWORK HEALTH DIGEST

Volume 7.17 - 19th October 2017

Questions relating to: The gut microbiota in older adults and the potential for probiotics. Type your answers below, download and save or print for your records, or print and complete by hand. Q.1

Describe how the gut microbiota of an older adult may typically differ from that of a younger adult.

Q.2

Describe at least two health outcomes that have been associated with a loss of gut microbial diversity.

Q.3

Describe at least two of the aims of the ELDERMET study.

Q.4

What is the evidence to suggest that residential setting and dietary intakes influence the gut microbial diversity of elderly subjects?

Q.5

What is the effect of antibiotics on the gut microbiota?

Q.6

What is the evidence to suggest that probiotics may be beneficial in care homes?

Q.7

What is the evidence to suggest that probiotics can reduce rates of C difficile infection in elderly subject?

Q.8

Explain why it is important to consider choice of strain when using or recommending a probiotic and what references/resources you might use to check advice on safety and quality criteria of probiotics.

Please type additional notes here . . .