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
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
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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
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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.
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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
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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.
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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
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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
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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.
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• 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
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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.
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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
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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).
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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
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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
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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.
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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
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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.
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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.
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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.
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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.
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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
po
rtio
n (
%) o
f su
bje
cts
wit
h s
ub
ject
ive
sym
pto
ms
of
the
com
mo
n c
old
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
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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.
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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
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Morinaga as your
partner for NPD
Here's your journey to an appealing probiotics product.
Contact information
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Email [email protected]
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probiotics-center