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How aging societies are creating opportunities for probiotics and postbiotics

Societies are aging quickly. In countries around the world, the number of people aged 60 years and older are at record levels and are forecast to grow higher still in the coming decades. The trend is creating opportunities for developers of probiotics and postbiotics to improve wellbeing by delivering clinically validated healthy aging products.

In 2019, Japan had 51 old-age dependents for every 100 people aged 20 to 64 years, making it the only country to have more seniors than working-age individuals.1​ The nine countries with the next highest old-age dependency ratios, none of which exceeded 39, were all outside of Asia.

The situation is forecast to change dramatically over the next 30 years. Ten countries are predicted to have old-age dependency ratios of 65 or higher by 2050. Four of the countries are in Asia, led by the 81 and 79 old-age dependency ratios forecast for Japan and the Republic of Korea. In total, the world is predicted to contain 2 billion people aged 60 years and older, up from 900 million in 2015.2

It will be critical to manage the health of those 2 billion people. As people age, they suffer chronic low-grade inflammation that contributes to a range of conditions including cardiovascular disease, diabetes, dementia and cancer.3​ At the same time, gastrointestinal disorders such as constipation and diarrhoea become more common.4,5

Research shows the immune system weakens, too, raising the risk of infection and reducing the effectiveness of vaccines.4,5​ Interest in maintaining immune health has intensified since the start of the COVID-19 pandemic, with sales of immunity-boosting ingredients rising and people vowing to continue their supplement regimes even after being vaccinated against the coronavirus.6,7

The gut microbiome also changes as people age, with researchers tracking a rise in the proportion of Bacteroidetes​ and a fall in the proportion of Firmicutes​.8​ Levels of Bifidobacterium​, a genus linked to good health, are lower in the elderly than in younger adults. Other changes include increases in the levels of Proteobacteria​.9,10

Morinaga Milk Industry has contributed to understanding of the effects of aging on the microbiome. The researchers showed increases in facultative anaerobes such as Escherichia coli​ at the expense of obligate anaerobes such as Bifidobacterium ​in the elderly.11

There is evidence the changes affect human health. Researchers have linked age-related changes in the gut microbiota to negative health outcomes, and found high levels of Bifidobacterium ​in people who live for 110 years or more.12–15​ Morinaga Milk’s own research showed metabolites made in the guts of elderly people can trigger or contribute to systemic age-related diseases in the elderly.16

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Validating probiotics in humans

The rapid growth in the number of seniors and understanding of the role the gut microbiome plays in healthy aging are creating opportunities to have significant effects on global wellbeing. To seize the opportunities, nutrition brands will need ingredients that are proven to have clinical efficacy against outcomes that matter to seniors. Recognizing that, Morinaga Milk has worked in recent years to clinically validate well-established probiotic strain Bifidobacterium longum​ BB536 in health aging.

Gut health

In the 50 years since the discovery of BB536, researchers have linked consumption of dairy products containing the strain to improvements in the frequency and characteristics of stools in all age groups to relieve constipation and diarrhea.17

Morinaga Milk built on that history of use by assessing the effect of giving BB536 to 123 seniors who were receiving enteral tube feedings.18​ The double-blind, placebo-controlled clinical trial linked 16 weeks of supplementation with BB536 to a significant change in the frequency of defecation. Across the trial and another placebo-controlled study of 83 seniors, BB536 restored regular bowel movements in people who previously defecated often and increased the prevalence of normally formed stools.

Immune health

Researchers have assessed the ability of BB536 to improve immunity in the elderly. In one study, 27 seniors took BB536 for five weeks, received an influenza vaccine at week three and were then randomized to receive either BB536 or placebo for 14 weeks.19

Fewer patients in the BB536 arm contracted influenza or suffered fever. The activity of natural killer cells and neutrophils increased over the five weeks when all participants received BB536, and stayed higher in the probiotic cohort after randomization. The researchers concluded the results suggest the use of BB536 reduces influenza and fever, most likely by improving innate immunity.

Cardiovascular health

To test the effect of BB536 on cardiovascular health, researchers randomized 33 adults to take either placebo or the probiotic strain in combination with red yeast rice extract, niacin and coenzyme Q10 for 12 weeks. Over that time, levels of multiple cardiovascular risk markets including total and LDL cholesterol fell significantly in the BB536 group compared to placebo.

Other research has associated lower levels of the lipids with reduced cardiovascular risk, pointing to the potential for the nutraceutical combination to support healthy heart aging.

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Investing in postbiotic R&D

Morinaga Milk is creating further opportunities to support healthy aging by investing in postbiotics. The emerging class of postbiotic products is defined by its use of non-viable microorganisms or cellular components and metabolites, as opposed to the live bacteria found in probiotics. As postbiotics lack live bacteria, they have a longer shelf life and are suitable for use in a wider range of formulations.

LAC-Shield, Morinaga Milk’s postbiotic, is a heat-killed version of a probiotic strain selected for its ability to trigger production of interleukin-12, a cytokine that activates innate and adaptive immunity.20​ As a postbiotic, LAC-Shield is heat tolerant and highly stable at a range of pHs, making it suitable for use in foods and beverages, as well as supplements.

Morinaga Milk has validated the efficacy of LAC-Shield in a clinical trial that randomized seniors to eat a jelly containing the postbiotic or a placebo for six weeks. The participants received an influenza vaccine at the midpoint of the study. In participants aged 85 years and older, consumption of LAC-Shield was associated with higher blood vaccine antigens and improved antibody responses.21

The clinical validation of B. longum​ BB536 and LAC-Shield has given nutrition brands the opportunity to develop healthy aging products that act on outcomes that are important to the growing number of seniors. By seizing that opportunity, brands stand to get ahead of a major, long-running trend and thereby grow sales while improving wellbeing.

 

References

1.      World Population Ageing 2019 Highlights. https://www.un.org/en/development/desa/population/publications/pdf/ageing/WorldPopulationAgeing2019-Highlights.pdf.

2.      Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health.

3.      Franceschi, C., Garagnani, P., Parini, P., Giuliani, C. & Santoro, A. Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol. 14, 576–590 (2018).

4.      Dumic, I. et al. Gastrointestinal Tract Disorders in Older Age. Can J Gastroenterol Hepatol 2019, 6757524 (2019).

5.      Montecino-Rodriguez, E., Berent-Maoz, B. & Dorshkind, K. Causes, consequences, and reversal of immune system aging. J. Clin. Invest. 123, 958–965 (2013).

6.      Immune health concerns here to stay. https://www.innovamarketinsights.com/press-release/immune-health-concerns-here-to-stay/.

7.      Polito, R. Monitor: Consumers plan steady or increased supplement use post-vaccination. https://www.newhope.com/market-data-and-analysis/monitor-consumers-plan-steady-or-increased-supplement-use-post-vaccination (2021).

8.      Ragonnaud, E. & Biragyn, A. Gut microbiota as the key controllers of ‘healthy’ aging of elderly people. Immun. Ageing 18, 2 (2021).

9.      Claesson, M. J. et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. U. S. A. 108 Suppl 1, 4586–4591 (2011).

10.    Biagi, E. et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One 5, e10667 (2010).

11.    Odamaki, T. et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 16, 90 (2016).

12.    Jeffery, I. B., Lynch, D. B. & O’Toole, P. W. Composition and temporal stability of the gut microbiota in older persons. ISME J. 10, 170–182 (2016).

13.    Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 488, 178–184 (2012).

14.    Biagi, E. et al. The gut microbiota of centenarians: Signatures of longevity in the gut microbiota profile. Mech. Ageing Dev. 165, 180–184 (2017).

15.    Biagi, E. et al. Gut Microbiota and Extreme Longevity. Curr. Biol. 26, 1480–1485 (2016).

16.    Yoshimoto, S., Mitsuyama, E., Yoshida, K., Odamaki, T. & Xiao, J.-Z. Enriched metabolites that potentially promote age-associated diseases in subjects with an elderly-type gut microbiota. Gut Microbes 13, 1–11 (2021).

17.    Wong, C. B., Odamaki, T. & Xiao, J.-Z. Beneficial effects of Bifidobacterium longum subsp. longum BB536 on human health: Modulation of gut microbiome as the principal action. J. Funct. Foods 54, 506–519 (2019).

18.    Kondo, J. et al. Modulatory effects of Bifidobacterium longum BB536 on defecation in elderly patients receiving enteral feeding. World J. Gastroenterol. 19, 2162–2170 (2013).

19.    Namba, K., Hatano, M., Yaeshima, T., Takase, M. & Suzuki, K. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly. Biosci. Biotechnol. Biochem. 74, 939–945 (2010).

20.    Arai, S. et al. Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice. PLoS One 13, e0199018 (2018).

21.    Maruyama, M. et al. The effects of non-viable Lactobacillus on immune function in the elderly: a randomised, double-blind, placebo-controlled study. Int. J. Food Sci. Nutr. 67, 67–73 (2016).

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