Probiotics and paraprobiotics for immunity

Probiotics and paraprobiotics

for immunity:

from science to

innovative solution

NutraIngredients Immunity Broadcast Series 2021 18 May | APAC

Chyn Boon Wong, PhD

Morinaga Milk Industry Co., Ltd

Copyright©Morinaga Milk Industry Co.,Ltd.All Rights Reserved.

Immune health trend

Immunity is a hot topic and the trend will stay. Consumers are actively looking for food and drinks that improve immune function.

Source: Mintel GNPD

The APAC market has the second most immunity-enhancing product launches in the last five years

https://www.gnpd.com/sinatra/shared_link/6a911b76-4dc0-4d47-8bb8-2ec80683ae4f


COVID-19 impact

Base: 1,200 Chinese internet users aged 18-59Source: KuRunData/Mintel

COVID-19 draws consumer attention on their health and wellbeing, especially boosting their immune system.

Opportunity exist for immunity support products to thrive in the current COVID-19 crisis.

Interest in food, drink and supplement carrying an immune-promoting effect surged at the beginning of 2020 and has remained elevated throughout the COVID-19 pandemic.

And the immunity trend is here to stay.


High demand for probiotics product

ProbioticsLive microorganisms that

confer a health benefit on the host when administered in

adequate amounts.

Salminen et al., 2020, Nutrients

2nd top trend in probiotics field

Source: Lumina Intelligence

Probiotics are the key ingredients used in the immunity market


Paraprobiotics are gaining traction

Paraprobiotics

Non-viable probiotics or inactivated probiotics or ghost

probiotics, which, when administered in sufficient amounts

confer benefits to the host.

Postbiotics

Compounds produced by microbes, released from food components or

microbial constituents, including non-viable cells that, when

administered in adequate amounts, promote health and wellbeing.

Salminen et al., 2020, Nutrients

Consumers show great interest in products that meet immunity needs.

Demand for immunity-enhancing food and drinks increases.

It opens an opportunity for paraprobiotics, largely due to its versatility.

Paraprobiotics have practical advantage than traditional probiotics.


How probiotics and paraprobioticswork on immunity?

ProbioticsLive microorganisms that confer

a health benefit on the host when administered in adequate

amounts. Effects o

f pro

bio

tics on

ly

Indirect effectRemain alive to reach the GIT and interact with the gut immune cells via growth and production of SCFA, vitamins, EPS, peptides, amino acids, fatty acids, and other metabolites. ↓◦ Modulate gut microbiota ◦ Improve gut barrier function ◦ Modulate gut metabolites ◦ Regulate immune responses↓Improvement of gut microenvironment (Mainly in large intestine)

Direct effectvia bacterial cell component ◦ Peptidoglycan◦ Lipotechoic acid ◦ Exopolysaccharide (EPS)↓Interaction with gut immune cells↓Immunomodulatory effects (mainly in small intestine)

ParaprobioticsHeat-killed non-viable probiotics, which, when administered in sufficient amounts confer benefits to the host.

and

par

apro

bio

tics

Effe

cts

of

pro

bio

tics


Morinaga pro/paraprobiotics portfolio

Infant & Children

Gut Immune Anti-allergy MentalWeight

ManagementHealthy Ageing

BB536 BB536 BB536 BB536

M-16V M-16V

M-63 M-63

M-63 B-3B. longum B. longum B. longum B. longum B. infantis B. breve

B. breveB. breve

B. infantisB. infantis

LAC-Shield

Immune

The main key drivers of our probiotics portfolio are clinical efficacy, stability, quality and naturalness.

BB536B. longum

M-63B. infantis


Focus on human strains

50 years of pioneering HRB probiotics

We have dedicated 50 years+ research efforts

on the genus Bifidobacterium and focused on

bifidobacterial strains that are genuinely

beneficial and naturally inhabiting the human

gut – HRB.

Paraprobiotics strain: Heat-killed L. paracasei MCC1849

Probiotics effect on immunityLAC-ShieldParaprobiotics effect on immunity

In recent years, with its innovative technology,

we have developed a paraprobiotic called LAC-

Shield that specifically addresses the increased

interest in immune health.


• Excellent stability profile • Quality assured probiotics ingredient

BB536: A well-researched HRB probiotic strain

• Long history of safe use • More than 40 years worldwide

• Global market opportunities

BB536B. longum

A HRB probiotic strain with multifunctional

effects

• More than 200 scientific studies • >80 clinical studies

• Proven clinical efficacy for all age groups

• Regulatory approved: • 2019: FDA GRAS for infant formula • 2009: FDA GRAS for foods • 1996: Japan FOSHU status


B. longum BB536 improves immunity in seniors

The immune system tends to get weaker with age, causing increased susceptibility to infections.

Thymus atrophy begins as early as puberty, and continues at a rate of about 1% per year.

Consequently, fewer naïve T cells are produced with time.

The ability of B cells to produce immunoglobulin, neutrophils and NK cells activities also declines with age.

Weaken immune system in seniors limits vaccine efficacy.

Influenza vaccine effectiveness decreases from 70–90% efficacy in healthy adults to 17–53% efficacy in the elderly.


The gut microbiota-immunity link

Gut microbiota and the immune system work in a mutual relationship and constantly shape each other. Any imbalance in the gut microbiome affects the immune system and vice-versa.

B. longum BB536 – a HRB strain, has been demonstrated to improve waning immunity in the elderly.

Two clinical studies show that administration of BB536 could stimulate neutrophil and NK cell activity, reduces the cases of influenza and fever, and increases IgA levels in the elderly subjects.

The gut microbiota can influence immune function

Akatsu et al., 2013. Journal of Parenteral and Enteral Nutrition; Namba et al., 2010. Bioscience, Biotechnology, and Biochemistry


Clinical efficacy of BB536 on senior’s immunity

*P <0.05 with χ2 test.

0

20

40

60

80

100

Week 0 Week 4 Week 6 Week 8 Week 12 Week 16

Perc

enta

ge o

f su

bje

cts

wit

h a

n a

nti

bo

dy

tite

r ≥2

0

A/H1N1

Placebo BB536

* +33%

Akatsu et al., 2013. Journal of Parenteral and Enteral Nutrition.

Elderly patients aged >65 years fed by enteral tube feeding (n=45)

BB536 group

5 x 1010 CFU/2g, twice/dayPlacebo group

12 weeks intervention period2 weeks run-in period

Vaccination Analysis

W4 W6

Analysis

W8

Analysis

W12

Analysis

W16

Effect of BB536 on influenza vaccination and natural

resistance in the elderly:

• Significant increase in A/H1N1 antibody titers ≥ 20

(p < 0.05).

• Tended to stimulate NK cells activity (p < 0.1);

Tended to increase IgA levels (p < 0.1).


Clinical efficacy of BB536 on senior’s immunity

Seniors who ingested BB536had better immunity. They had lesser cases of influenza infection and fever (p = 0.041).

BB536 stimulated NK cell activity and the neutrophils phagocytic and bactericidal activities.

Namba et al., 2010. Bioscience, Biotechnology, and Biochemistry.

Seniors aged >65y residing in a nursing home (n=27)

BB536 group100 billion CFU

(2g/day)

Placebo group

Period 2: 14 weeksPeriod 1: 6 weeks

BB536 intake

Vaccination Analysis

W3 W5

BB536 enhances body’s defense system against influenza infection


Innovative opportunities in APAC

Consumer awareness continues to heighten and it opens door for innovative development with clinically-proven probiotic strain, e.g. the HRB strain B. longum BB536.

In the APAC region, consumers especially among seniors, are interested in food, drink & healthcare products with immune health improving functional benefits, providing exciting opportunities to brand manufacturers.

57%

32%

4% 5%2%

66%

18%

9%6%

2%

60%

25%

8% 7%

0%

65%

16%12%

6%1%

71%

14%10%

2% 2%

0%

20%

40%

60%

80%

Asia Pacific Europe Latin America North America Middle East & Africa

% o

f la

un

che

s

Global: food, drink & healthcare launches with a seniors (aged 55+) claim, by region, Apr 2015-Mar 2020

Apr 2015-Mar 2016

Apr 2016-Mar 2017

Apr 2017-Mar 2018

Apr 2018-Mar 2019

Apr 2019-Mar 2020

BB536 application examples

(not limited to age groups):

• Dairy products

• Dietary supplement

• Chocolate

• Powdered formula

Source: Mintel GNPD

https://www.gnpd.com/sinatra/shared_link/b56b3550-19cf-429d-a20e-54f1a10306c7


LAC-Shield™

LAC-Shield is a patented clinically proven heat-killed

strain of beneficial lactic acid bacteria that possess

excellent immune-enhancing activity.

LAC-Shield was named for its unique immunological

function serving as a "shield" to protect the human

body against invading enemies.

Heat-killed L. paracasei MCC1849

LAC-Shield acquired Self-Affirmed GRAS status in 2018.


Beyond probiotics

Lactic acid bacteria that protect you

Add health to any food with the same

deliciousness

Since it is heat-killed, it can be used for any food.

Add value with a small

amount

LAC-Shield™ Formulation Benefits:

LAC-Shield is heat tolerant and highly stable to pH and other conditions

Versatile F&B application potential

LAC-Shield has no major issues in:

✓ Harsh manufacturing conditions

✓ Long product shelf life

✓ Stress during gastrointestinal transit


Beyond probiotics

Used by more than

450companies

in 1,000+ typesof products in Japan

Achievements in Japan domestic BtoB business

LAC-Shield has been used by many domestic food and

beverage manufacturers, restaurants, retailers such as

CVS, etc.

To date, LAC-Shield has been incorporated into more

than 1000 types of products in Japan.

Endless opportunities in the global marketplace

LAC-Shield has also been widely used by many food

and beverage manufacturers worldwide. It is

especially popular in the APAC region.


LAC-Shield™ in action

Lactic acid bacteria L. paracasei MCC1849

Immune cells (mice)

Immuno-stimulatory substance

(IL-12 production)

乳酸菌株（殺菌体）

L. paracaseiMCC1849

免疫賦活活性(%) LAC-Shield™

The production of immuno-stimulatory substance (IL-12) by immune cells stimulated with heat-killed bacteria was measured.

Imm

un

o-s

tim

ula

tory

act

ivit

y (%

)

Lactic acid bacteria strains (heat-killed)

One in a thousand strains

LAC-Shield is an elite lactic acid bacteria with excellent

immune activity selected from among the several

thousand strains of lactic acid bacteria stocked by

Morinaga Milk Industry Co., Ltd.

LAC-Shield greatly surpasses the other lactic acid bacteria

in immune activity.

It has a high ability to induce the production of

interleukin-12 (IL-12) – a cytokine with important

regulatory functions, bridging innate and adaptive

immunity.


Function of IL-12

Interleukin-12 (IL-12) is an important regulatory cytokine.

What is the role of IL-12?

✓ Regulates T-cell and natural killer-cell responses.✓ Induces the production of interferon-γ (IFN-γ) ✓ Favours the differentiation of T helper 1 (TH1) cells

IL-12 is an important link between innate resistance and adaptive immunity.


Blood samples

Health effect of LAC-Shield™

Vaccine antibody titer against type B

Type A/H1N1 Type A/ H3N2 Type B

Vaccine antibody titer against type A/H1N1 Vaccine antibody titer against type A/ H3 N2

0.5

1

1.5

2

2.5

対照群シールド乳酸菌

P<0.05

Control group LAC-Shield

P<0.01 P<0.01

0.5

1

1.5

2

2.5

対照群シールド乳酸菌Control group LAC-Shield

0.5

1

1.5

2

2.5

対照群シールド乳酸菌

P<0.05

Control group LAC-Shield

• Subject: Elderly people aged 65 and over• Intervention: LAC-Shield (10 billion) jelly or normal jelly• Endpoint: Immune response to influenza vaccination

Super-elderly people aged 85 and over (11 in the control group, 16 in LAC-Shield group)* The graph below shows the antibody titers against each of the three types of antigens.

Maruyama et al., Int J Food Sci Nutr. (2016)

Placebo (n=21)

LAC-Shield (n=21)

Intervention period: 6 weeks

Vaccination at Week 3

Blood samples

Effect of LAC-Shield intake:

• Enhance the immune response to vaccination in super-elderly people with decreased immunity due to aging.


Health effect of LAC-Shield™

• Subject: Healthy women over 18 years old• Intervention: LAC-Shield (10 billion or 30 billion/day)

or placebo• Ingestion period: 12 weeks

Murata et al. Benef Microbes (2018)

Analysis of data from a population of individuals who experienced the common cold during the last year

* A significant difference was found between two groups (P<0.05)

＊

30.billion-cell groups

10 billion-cell groups

Pro

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ReductionEffects of LAC-Shield on healthy women who are prone to common cold:

• Reduced subjective symptoms of common cold• Reduced number of symptomatic days and

symptom scores• Maintain a positive mood


New opportunities with LAC-Shield™ and BB536

LAC-Shield

Immune health

HRB Probiotics Paraprobiotics

Innovative opportunities exist for LAC-Shield and BB536 to win the probiotics game. They can even be combined to provide a comprehensive effect of pro and paraprobiotics on immunity.


Key Takeaways

• Probiotics is wildly popular in the immune health category.

• Paraprobiotics is gaining traction and heading in a similar trajectory.

• However, not all pro/paraprobiotics are the same. Their health-promoting effects have to be well-tested in human clinical studies.

• The HRB strain of B. longum BB536 is clinically proven to enhance senior’s resistance on influenza infection.

• LAC-Shield – a paraprobiotic strain- is clinically proven to enhance immune response of influenza vaccine in super-elderly people and prevent common cold in healthy adults.

• Incorporation of BB536 or/and LAC-Shield opens door for innovative product development.

LAC-Shield

Ingredients for differentiation


Morinaga as your

partner for NPD

Here's your journey to an appealing probiotics product.

Contact information

Phone Number+81 3-3798-0152

Email [email protected]

Websitehttps://morinagamilk.co.jp/english/

https://morinagamilk-ingredients.com/

LinkedInhttps://www.linkedin.com/company/morinaga-

probiotics-center

Documents

Probiotics and paraprobiotics for immunity