HOWARU Shape - vitafoods.eu.com€¦ · Preventing type II diabetes ... Cell culture studies Mouse studies Mouse studies MetsProb clinical study MetsProb clinical study B420™ improves

HOWARU® ShapeA probiotic / synbiotic with benefits

beyond weight management

Dr. Johanna Maukonen,

Global Health & Nutrition Science Leader,

DuPont Nutrition & Biosciences

Information Classification: General

1. Probiotic effects

2. Scientific evidence on Bifidobacterium

animalis subsp. lactis B420™ &

Metabolic health

3. Conclusions

CONTENTS OF THIS PRESENTATION

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MODULATORS OF OUR MICROBIOTA COMPOSITION

Antibiotics

Diet,

including prebiotics Probiotics

Large effect Moderate effects Small but

specific effects

Microbiota and immune system

FUNCTION

Lahti et al. 2013 Peer J 1e:32. Lactobacillus rhamnosus GG intervention does not alter microbiota composition Copyrig

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Information Classification: GeneralCopyrig

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Digestive health

➢ Improved symptoms of IBS

➢ Reduced risk of diarrhea

• Antibiotic associated

• C.difficile associated

• Necrotizing enterocolitis

• Infectious

➢ Benefits on IBD are unclear

Immune health

➢ Reduced risk of cold

➢ Potentially alleviation of allergic symptoms

➢ Reduced risk of eczema and atopic dermatitis

especially if probiotics started during

pregnancy

Metabolic health

➢ Total and LDL cholesterol lowering

➢ Preventing obesity

➢ Preventing type II diabetes

➢ Improved hepatic encephalopathy

➢ Non-alcoholic fatty acid liver disease

PROBIOTIC HEALTH EFFECTS: META-ANALYSES

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SUSTAINABLE DIFFERENTIATION

Strains provide benefits | Genus and species don't do it

Identification down to strain level needed | Strain designation needed to tie to science

Bifidobacterium animalis subsp. lactis

Genus Species Subsp. Strain

HOWARU® Shape

B420™



2. Scientific evidence on

Bifidobacterium animalis subsp.

lactis B420™ & Metabolic health

3. Conclusions


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Global Health & Nutrition Science Product development pipeline

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Unique clinical documentation

Bifidobacterium animalis subsp. lactis 420 (B420™) for metabolic health – a decade of research

2007 & 2015 2008-2013 2013-2016 2013-2016 2017-2018

Cell culture studies Mouse studies Mouse studies MetsProb clinical study MetsProb clinical study

B420™ improves

epithelial barrier

function

B420™ improves

metabolic health

and gut barrier

function

B420™ +

Litesse® Ultra™

improves meta-

bolic health

B420™ with or

without Litesse®

Ultra™ controls

body fat mass

B420™ with or

without Litesse®

Ultra™ increases

abundance of

Akkermansia spp. in

the fecal samples

Putaala et al.

Res Microbiol 2008

Mokkala et al.

Nutr Res 2016

Amar et al.

EMBO Mol Med 2011

Stenman et al.

Benef Microbes 2014

Stenman et al.

Diabetol Metab Syndr

2015

Garidou et al.

Cell Metab 2015

Stenman et al.

EBioMedicine 2016

Hibberd et al.

Beneficial Microbes 2018

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B420™ SUPERNATANT IMPROVES EPITHELIAL

INTEGRITY IN A CELL MODEL

Putaala et al. Res Microbiol 2008

➢ Epithelial integrity is a

key function of the GI-

tract

➢ Its disturbance is

connected to metabolic

disorders such as

obesity

➢ The finding of improved

epithelial integrity by

B420™ led to testing it

for HOWARU® Shape

* P < 0.05

** P < 0.01

*** P < 0.0001

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B420™ AMELIORATES WEIGHT GAIN

IN MICE

➢ Reduction in weight

gain

➢ Reduction of

accumulation of fat

mass on an unhealthy

diet

➢ First proof of concept

of B420™ for weight

management

Stenman et al. Beneficial microbes 2014

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➢ B420™ (1B CFU)

significantly improved

glucose tolerance in

high-fat diet-induced obese

mice

➢ Impaired glucose tolerance

suggests a greater risk of

developing diabetes and

cardiovascular disease

➢ Improving glucose

tolerance could be useful in

preventing / reducing risk

for type 2 diabetes or non-

insulin-dependent diabetes

mellitus (NIDDM)

B420™ IMPROVES GLUCOSE

TOLERANCE IN OBESE MICE

Stenman et al. 2014. Beneficial microbes.

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6 M

on

ths

Follow-up:

+1 month

Control: microcrystalline cellulose (MCC)

Probiotic: B420™ + MCC

Prebiotic: Litesse® Ultra™ polydextrose

Synbiotic: Litesse® Ultra™ + B420™

Ba

se

lin

e

Probiotics and prebiotics for controlling body fat mass

• Randomized, double-blind, multicenter study

• Study design and execution follows ICH-GCP

• 225 Finnish participants with BMI 28-34.9, otherwise healthy

• Primary outcome: relative change in body fat mass

Stenman et al. EBioMedicine 2016

HOWARU™ Shape – UNIQUE CLINICAL STUDY

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THE STUDY POPULATIONS, AS PRE-DEFINED


Randomized

(n=225)

Intention-to-treat

(n=209)

Placebo: 56

Litesse® Ultra™: 53

B420™: 48

Litesse® Ultra™ + B420™: 52

Per protocol

(n=134)

Placebo: 36

Litesse® Ultra™: 36

B420™: 25

Litesse® Ultra™ + B420™: 37

Excluded

(n=16)

Dropped out before the next

study visit after baseline

Excluded

(n=75)

• Product non-compliance

• End-of-study visit not completed

• Use of antimicrobials during the

intervention

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STATISTICAL ANALYSES – TWO ALTERNATIVE WAYS

• Each group is individually compared to

placebo

• Group-wise tests are corrected for multiple

comparisons

• Allows analysis by factor, which improves

statistical power

• Does not give a clear result for the

combination group

Pre-defined primary analysis

ANCOVA + Dunnett’s test Factorial analysis

Post hoc analysis

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1.4 KG LESS TOTAL BODY FAT MASS COMPARED

TO PLACEBO

Primary outcome: B420™ + Litesse® Ultra™ controls total body fat mass 4.5% (1.4 kg) less fat

mass vs placebo P=0.02

4% (1.4 kg) less fat mass

vs non-B420™ groupsStatistical analyses:

ANCOVA values

Factorial analysis


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… OF WHICH 1.2 KG IS LOCALIZED TO TRUNK FAT

MASS

-6.3% (-1.2 kg) less fat mass

vs. non-B420™ groups

6.7% (1.2 kg) less fat mass

vs. placebo P = 0.008

Statistical analyses:

ANCOVA values

Factorial analysis


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2.6 CM SMALLER WAIST CIRCUMFERENCE COMPARED

TO PLACEBO

2.7% (2.6 cm)

smaller waist size

2.4% (2.4 cm)

smaller waist size

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ANCOVA values

Factorial analysis



IMPROVING LEAN BODY MASS %

Improved body composition in Litesse® Ultra™ + B420™ group

0.95 kg

more lean

body mass

(+2.0%)

1.0 kg less

body weight

(1.2%)


ANCOVA values

Factorial analysis

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B420™ ALONE OR IN COMBO WITH LITESSE® ULTRA™ REDUCES

ENERGY INTAKE

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The fecal microbiota

composition

➢ 16S rRNA sequencing:

baseline, 2 mo, 4 mo, 6

mo, and +1 mo post-

intervention

➢ correlation to obesity-

related clinical biomarkers

B420™: Lactobacillus and

Akkermansia

Heat map with two-way hierarchical

clustering of genus-summarized microbiota

abundance after 6 months of intervention

in the Per Protocol population

FECAL MICROBIOTA

Hibberd et al., Beneficial microbes 2019

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Litesse® Ultra™ (LU) + B420™:

Akkermansia ,

Christensenellaceae , while

Paraprevotella

Christensenellaceae was

consistently increased in the

LU and LU+B420™ groups

➢ correlated negatively to

waist-hip ratio and energy

intake at baseline,

➢ correlated negatively to

waist-area body fat mass after

6 mo treatment with LU+B420™

B420™ alone and in combination

with LU modified the gut microbiota

FECAL MICROBIOTA MODIFICATION

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Hibberd et al., Beneficial microbes 2019


➢ B420™ prevented an increase in

zonulin concentration in humans

➢ Zonulin is a regulator of epithelial

and endothelial barrier function.

High levels indicate high

intestinal permeability

➢ High intestinal permeability is a

possible cause of “leaky gut

syndrome”

➢ symptoms include bloating,

gas, cramps, food

sensitivities, aches, and pains

➢ High intestinal permeability could

be related to autoimmune and

metabolic disorders

B420™ CONTROLS INTESTINAL PERMEABILITY

IN HUMANS


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➢ The levels of high-sensitivity

C-reactive protein (hsCRP)

remained lower in those

taking B420™ as compared

to those that did not take

B420™

➢ hsCRP is an acute-phase

protein released into the

blood by the liver during

inflammation

➢ hsCRP levels rise in

response to inflammation

➢ Inflammation can negatively

affect organs

B420™ HAS A POSITIVE EFFECT ON

INFLAMMATION


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2

3



2. Scientific evidence on Bifidobacterium

animalis subsp. lactis B420™ &

Metabolic health

3. Conclusions


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Conclusions

B420™

B420™ +

Litesse® Ultra™

Has a weight management benefit ✓✓

Improved body composition

(fat/lean ratio)

Controlled body fat mass ✓ ✓

Increased lean mass ✓

Controlled energy intake ✓ ✓

Controlled trunk fat mass ✓ ✓

Controlled waist circumference ✓ ✓

Supports healthy microbiota

associated with metabolic health✓ ✓

Promotes growth of beneficial bacteria ✓ ✓

Promotes an increase in

Akkermansia, which is linked to lean

and healthy body weight

✓ ✓

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26

Thank you for your attention !~40 team members:

➢ 50% PhDs➢ 25% MScs➢ 20% technicians➢ secretary➢ occasional visitors

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DuPont™, the DuPont Oval Logo and Danisco® logo are trademarks or registered trademarks of DuPont or its affiliates. Copyright © 2019 DuPont de Nemours Inc. All rights reserved.

Nothing contained herein shall be construed as a representation that any recommendations, use or resale of the product or process described herein is permitted and complies with the rules or regulations of any countries, regions, localities, etc., or does not infringe upon patents or other intellectual property rights of third parties.

The information provided herein is based on data DuPont believes to be reliable, to the best of its knowledge and is provided at the request of and without charge to our customers. Accordingly, DuPont does not guarantee or warrant such information and assumes no liability for its use. If this product literature is translated, the original English version will control and DuPont hereby

disclaims responsibility for any errors caused by translation. This document is subject to change without further notice.

Documents

HOWARU Shape - vitafoods.eu.com€¦ · Preventing type II diabetes ... Cell culture studies Mouse studies Mouse studies MetsProb clinical study MetsProb clinical study B420™ improves