0.1 Your Health 020820

INFANT & YOUNG CHILDREN’S HEALTH
Your Health – Our Science

Bifidobacterium lactis, BB-12® – The
worlds most documented Bifidobacterium
Mie Kristensen, M.Sc
Scientific advisor – Chr. Hansen
© 2019 Chr. Hansen A/S. All rights reserved.
Agenda
01 Who are we, about Chr. Hansen
02 The human microbiome
03 The first 1000 days and the microbiome
04 Bifidobacterium lactis, BB-12® by Chr. Hansen
05 BB-12® - backed by > 100 clinical trials
06 Key takeaways
2 © 2019 Chr. Hansen A/S. All rights reserved.

Agenda

05 BB-12® - backed by > 100 clinical trials
06 Key takeaways

 B
We are
 Founded in 1874 in Copenhagen by Danish pharmacist
Christian D.A. Hansen
 Christian D.A. Hansen started his business producing
rennet from ruminants
 Today a global supplier of bioscience based ingredients to
the food, health, pharmaceutical and agricultural
industries
 We mainly produce cultures and dairy enzymes,
probiotics and natural colors
 More than 3400 employees

Chr. Hansen make natural solutions with enzymes and microbes
• Chr. Hansen was ranked as the most sustainable company in the world by the
media and research firm Corporate Knights, anounched during the world
economic forum in Switcherland
• In the running was all publicly listed companies with a reveniue above 1 billion
dollars, which was evaluated on 21 key performance indicators
• Chr Hansen scores 100 % on the ‘clean revenue’ indicator, reflecting that our
products have clear environmental and cirtain social benefits.

Agenda
05 BB-12® - backed by >100 clinical trials
06 Key takeaways

Agenda

06 Key takeaways

At best you are 50% you ….
50 % human. 50 % bacteria

Valerie Brown, Psmag, 2010
• We screen hundreds of bacteria
• Optimize selected bacteria
• Animal models help us understand what the bacteria do and

help cast light on organ interactions and biomarkers
• The bacteria we believe in, we upscale and study in human

clinical trials

Agenda
06 Key takeaways

Agenda

06 Key takeaways

Establishing a healthy microbiome in early life
- The first 1000 days a window of opportunity
When a baby is born the relative abundance of gut

bacteria is relatively low.
The development follows a universal trend, with a window

of bifidobacterial dominance
The early life microbiome has long term consequences for

health
Figure from ref 1
12
1Compiled from Korpela & de Vos, Curr Opin Microbiol. 2018
Bifidobacteria help developing a healthy immune
system during the first 1000 days
Bifidobacteria help educating the developing immune system towards

tolerance to foreign and “self” antigens
A balanced immune system reduces the risk of atopic and autoimmune

issues
Th1, Treg, Th2, Th17 are

important T-cells in the
immune system. An
imbalance can increase the
risk of getting atopic and
autoimmune issues.
Bifidobacteria help to
balance the Immune
system.

Unwanted consequences of todays society leads to lack of Bifidobacteria
in the infant gut
C-section Use of antibiotics Formula feeding
Disturb the infant gut development

Formula fed infants have a lower amount of
bifidobacteria
Breastfed Formula Fed
Bifidobacteria
Bacteroidetes
Proteobacteria
Firmicutes
Other
15© 2019 Chr. Hansen A/S. All rights reserved.

Azad et al., CMAJ, 2013
Low numbers of Bifidobacteria are associated with long-term health
Overweight Colic Atopic dermatitis
Rautava in: Isolauri E, Sherman PM, Walker WA (eds): Intestinal Microbiome, 2017
Probiotic supplementation of infants reduce risk of certain diseases
Probiotic supplementation of infants reduce risk of certain diseases
Overweight Colic Atopic dermatitis
Rautava in: Isolauri E, Sherman PM, Walker WA (eds): Intestinal Microbiome, 2017
Agenda
06 Key takeaways

Agenda

06 Key takeaways

Superior survival through the gastrointestinal tract
Using the TIM system, modelling the passage through the stomach and small intestine, Bifidobacterium lactis, BB-12® shows superior survival
compared to other Bifidobacteria
Cumulative ileal recovery

CFU
1 1
1 0
1 0
1 0 BB-12
B B - 1 2
r e c o v e r y
9
1 0
DUODENUM 1 0
8
ile a l
( C F U )
1 0
7
B. longum
B . lo n g u m
JEJUNUM
u la t iv e
6
1 0
5
Survival of Bifidobacteria:
ILEUM
1 0
BB-12®: 74% of intake
C u m
1 0
4
B. longum: 0.02% of intake

3
1 0
0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0
Time (min)
T im e ( m in )

Origin & Safety of Bifidobacterium lactis, BB-12®
 Originates from Chr. Hansen’s collection of cultures
 Identified as Bifidobacterium animalis subsp. lactis
 Used worldwide since 1985 with no known reported adverse events
 Tested in clinical studies with no known reported adverse events
 GRAS (Generally Recognized As Safe) notified by FDA
 QPS (Qualified Presumption of Safety) granted by EFSA

Bifidobacterium lactis, BB-12®
– the worlds best documented probiotic Bifidobacterium
Documented efficacy of Bifidobacterium lactis, BB-12®

 Described in more than 300 scientific publications
 Supported by more than 100 clinical studies
 Documented effect within gastrointestinal and immune function
 Tested in new-born preterm infants to elderly within various health areas
Number of published scientific articles on Bifidobacteria

0 50 100 150 200 250 300
BB-12®
BB-12® logo™ and BB-12® are trademarks of Chr. Hansen A/S

22© 2019 Chr. Hansen A/S. All rights reserved.
How the strain Bifidobacterium lactis, BB-12® works
The proposed mode of action of Bifidobacterium lactis, BB-12®
Site of action Intestinal lumen
Small intestine Mucus
Colon
Intestinal cells
Immune cells
23
The strain BB-12®

increase
Bifidobacterium
abundance
Intestinal lumen
Mucus
Intestinal cells
Immune cells
24
The strain BB-12® may modify

the microbiota in infants with
intestinal dysbiosis, e.g. by
producing antimicrobial Intestinal lumen
substances and competing
with the harmful bacteria for
adhesion sites in the intestine Mucus
Intestinal cells
Immune cells
25
Intestinal lumen
The strain BB-12®

helps improve bowel
Mucus
functions, e.g. by
stimulating peristalsis
Intestinal cells
Immune cells
26
Intestinal lumen
Mucus
Intestinal cells
The strain BB-12®
regulates the immune
response and may
beneficially impact the Immune cells
immune function e.g. by
maturating and
activating immune cells
27
Agenda
06 Key takeaways

Agenda

06 Key takeaways

Health benefits must be
demonstrated!

Bifidobacterium lactis, BB-12® supports
Bifidobacter-
ial count8 Update picture to IF
A reduced Reduction of
antibiotic eczema
use3 severity9
Nosocomial
Diarrhea
diarrhea
prevention9
prevention10
Respiratory Reduce
infection constipation
prevention1-3 Reduction of 11,12
colic4,5
1Taipale et al. Br J Nutr, 2011;105:409-41; 2 Taipale et al, Pediatric Research, 2016; 79:65-69. 3Rautava S et al. Br J Nutr 2009;101:1722-1726; 4Nocerino et al., ESPGHAN meeting 2019
; 5In prep. 6Vlieger et al. Br J Nutr, 2009;102:869-875; 7Chouraqui et al. Journal of pediatric gastroenterology and nutrition 2004, 38(3): 288-292; 8Langhendries et al. Journal of Pediatric
Gastroenterology and Nutrition 1995, 21(2): 177-181; 9Isolauri et al. Clinical and Experimental Allergy, 2000;30:1604-1610; 10Weizman et al. Pediatrics, 2005;115:5; 11 Pitkala et al, J Nutr,
2007; 11(4):305-11; 12 Eskesen et al, Br J Nutr, 2015; 114:1-9
2 new positive studies on  2 Randomized, double-blinded, parallel placebo
Bifidobacterium lactis, BB-12® and colic controlled using the same product and dose (1 bill
CFU/day)
 Inclusion/exclusion criteria according to ROME III
Study #1  Two different populations

Italy N=80
 Same primary endpoint:
 Intervention success defined as Numbers
of Responders , e.g. infants experience a
decrease of at least ≥50% in daily average
crying time at end of treatment
 Crying time recorded 24 h/day
 One study published and one study publication in

Study #2 preparation phase
China N=120

Italien colic study
Methods
 Randomized, double-blind, placebo-controlled

 80 breast fed infants (≤7 weeks) diagnosed with
infantile colic
 1 billion CFU/day BB-12® oil drops or placebo
 Parents reported daily in validated diary:

 Number and duration of crying episodes
 Number of bowel movements
 Stool consistency
 At baseline and at the end of treatment, stool

samples were collected from all study subjects for
gut microbiota analysis
Nocerino et al. Aliment Pharmacol Ther 2019, 51(1): 110-120

Study endpoints
 Endpoints
 Primary:
 Rate of infants with a reduction of ≥50% of mean daily
crying duration after 28 days of supplementation
 Secondary:
 Number of crying episodes
 Infant’s mood
 Number of bowel movements and stool consistency
 Gut microbiota composition, immunity peptides and
SCFAs
34
Scientific evidence
Bifidobacterium lactis, BB-12® effective in managing colic
Number of infants with a ≥50% reduction of duration of Additional results

crying during 28 days
• Mean number of daily crying episodes
100 descreased in the BB-12® group (p<0.05)
• Mean daily stool frequency decreased in
* both groups but the effect was
80
significantly higher in the BB-12® group
• Stool consistency was similar between
60 80% the 2 groups.
% Infants
40
20 33%
0
Placebo Bifidobacterium (BB-12®)
* p<0.0001

Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and eczema
Design
• Randomized, double-blind, placebo-controlled
• 27 infants, average age 4.6 months
• Infants breastfed and presented with eczema
• Infants weaned to hydrolyzed whey formula with LGG®, BB-12® or
no probiotics
• 0.3 CFU/g IF of LGG® or 1 billion CFU/g IF of BB-12®
• 6-7 months intervention
• Endpoints
• Extend and severity of eczema
• Growth and nutrition
• Concentration of circulating cytokines/chemokines
36
Isolauri et al. Clinical and Experimental Allergy, 2000;30:1604-1610
Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and eczema
The SCORAD score

SCORAD score at baseline and after 2 months of intervention decreased significantly
20 both from baseline and
compared to a placebo
16 hydrolyzed formula
when babies was
13.4 weaned to a hydrolyzed
formula containing BB-
12®1
10
Bifidobacterium (BB-12®)
significantly decreased the
extend and severity of
eczema after two months of
supplementation. After 6
months the median SCORAD
0 score in all groups was 0.
0
Baseline Placebo formula BB-12® No change was seen in
supplemented growth and nutrition status.
formula
37 © 2019 Chr. Hansen A/S. All rights reserved. Isolauri et al. Clinical and Experimental Allergy, 2000;30:1604-1610
Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and respiratory infections
Design
 Randomized, double-blind, placebo-controlled
 109 infants
 10 billion CFU/day
 6-7 months intervention
 Endpoints
 Incidence of acute respiratory infections and acute
otitis media
 Recovery of BB-12®

Taipale et al, Br J Nutr, 2011; 105:409-41
Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and the respiratory tract
infections in children is promising
31% fewer children
experienced
respiratory tract
Number of infants experiencing respiratory tract infections infections after 6
100 months of
supplementation with
90
-31% Bifidobacterium
80 (BB-12®)1
70
60
% Infants
50 Even after continuing the

40 intervention for 2 years
in total, fewer children in the
30 Bifidobacterium (BB-12®)
20 supplemented group
experienced respiratory
10 infections compared to the
0 placebo group2
Placebo BB-12®
39 © 2019 Chr. Hansen A/S. All rights reserved. 1 Taipale et al, Br J Nutr, 2011; 105:409-41 | 2 Taipale et al, Pediatric Research, 2016; 79:65-69
Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and diarrhea in infants
Design
• Randomized, double-blind, placebo-controlled
• 90 infants from child care centers
• ≥0.1 billion CFU/day in infant formula
• Average of 140 days intervention
• Endpoint
• Prevention of diarrhea
40 Chouraqui et al. Journal of pediatric gastroenterology and nutrition 2004, 38(3): 288-292
Scientific evidence
Scientific evidence on Bifidobacterium lactis, BB-12® and nosocomial diarrhea in infants
Number of infants experiencing diarrhea Number of days with diarrhea

% 100 3
Days
90
80 -46%
70 2
60 -50%
50
40
30 1
20
10
0 0
Placebo BB-12® Placebo BB-12®

Chouraqui et al. Journal of pediatric gastroenterology and nutrition 2004, 38(3): 288-292
Key takeaways
01 02 03
Microbiome – countless The infant microbiome Health benefits must

opportunities impacts
be demonstrated
Microbiome research holds The early life microbiome The Bifidobacterium lactis,
a well of potential targets – has long term consequences BB-12® strain has been
this is something we are for health and has e.g. investigated in more than
committed to explore at Chr. shown to be associated 100 clinical trials and shown
Hansen with: great effect within:
• Overweight • Colic
• Colic • Atopic dermatitis
• Atopic dermatitis • Prevention of respiratory
tract infections
• Diarrhea prevention

Thank you for your attention
50 % human. 50 % bacteria At best you are 50% you ….

Valerie Brown, Psmag, 2010

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INFANT & YOUNG CHILDREN’S HEALTH

Your Health – Our Science

01 Who are we, about Chr. Hansen

02 The human microbiome

03 The first 1000 days and the microbiome

04 Bifidobacterium lactis, BB-12® by Chr. Hansen

05 BB-12® - backed by > 100 clinical trials

2 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

3 © 2019 Chr. Hansen A/S. All rights reserved.

4 © 2019 Chr. Hansen A/S. All rights reserved.

5 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

02 The human microbiome

03 The first 1000 days and the microbiome

04 Bifidobacterium lactis, BB-12® by Chr. Hansen

05 BB-12® - backed by >100 clinical trials

6 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

7 © 2019 Chr. Hansen A/S. All rights reserved.

8 © 2019 Chr. Hansen A/S. All rights reserved.

• Optimize selected bacteria

• Animal models help us understand what the bacteria do and

• The bacteria we believe in, we upscale and study in human

9 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

02 The human microbiome

03 The first 1000 days and the microbiome

04 Bifidobacterium lactis, BB-12® by Chr. Hansen

05 BB-12® - backed by >100 clinical trials

10 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

11 © 2019 Chr. Hansen A/S. All rights reserved.

When a baby is born the relative abundance of gut

The development follows a universal trend, with a window

The early life microbiome has long term consequences for

Figure from ref 1

Bifidobacteria help educating the developing immune system towards

A balanced immune system reduces the risk of atopic and autoimmune

Th1, Treg, Th2, Th17 are

13 © 2019 Chr. Hansen A/S. All rights reserved.

C-section Use of antibiotics Formula feeding

Disturb the infant gut development

Breastfed Formula Fed

15© 2019 Chr. Hansen A/S. All rights reserved.

Overweight Colic Atopic dermatitis

Overweight Colic Atopic dermatitis

01 Who are we, about Chr. Hansen

02 The human microbiome

03 The first 1000 days and the microbiome

04 Bifidobacterium lactis, BB-12® by Chr. Hansen

05 BB-12® - backed by >100 clinical trials

18 © 2019 Chr. Hansen A/S. All rights reserved.

01 Who are we, about Chr. Hansen

02 The human microbiome

03 The first 1000 days and the microbiome

04 Bifidobacterium lactis, BB-12® by Chr. Hansen

19 © 2019 Chr. Hansen A/S. All rights reserved.

Cumulative ileal recovery

BB-12®: 74% of intake

B. longum: 0.02% of intake

20 © 2019 Chr. Hansen A/S. All rights reserved.

 Originates from Chr. Hansen’s collection of cultures