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BACKGROUND OBJECTIVE Effect of Probiotic B.lactis Bl-04 TM on Innate and Adaptive Host Responses to Experimental Rhinovirus Infection 1 DuPont Nutrition & Health Active Nutrition Sokeritehtaantie 20 02460 KANTVIK, FINLAND E-mail: [email protected] The information contained herein is based on data known to DuPont or its affiliates at the time of preparation of the information and believed by them to be reliable. This is business-to-business information intended for food, beverage and supplement producers, and is not intended for the final consumer of a finished food, beverage or supplement product. The information is provided “as is” and its use is at the recipient’s sole discretion and risk. It is the recipient’s sole responsibility to determine the suitability and legality of its proposed use of DuPont products for its specific purposes. Information and statements herein shall not be construed as licenses to practice, or recommendations to infringe, any patents or other intellectual property rights of DuPont or others. DUPONT HEREBY EXPRESSLY DISCLAIMS (I) ANY AND ALL LIABILITY IN CONNECTION WITH SUCH INFORMATION, INCLUDING, BUT NOT LIMITED TO, ANY LIABILITY RELATING TO THE ACCURACY, COMPLETENESS, OR USEFULNESS OF SUCH INFORMATION, AND (II) ANY AND ALL REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO SUCH INFORMATION, OR ANY PART THEREOF, INCLUDING ALL REPRESENTATIONS AND WARRANTIES OF TITLE, NONINFRINGEMENT OF COPYRIGHT OR PATENT RIGHTS OF OTHERS, MERCHANTABILITY, FITNESS OR SUITABILITY FOR ANY PURPOSE, AND WARRANTIES ARISING BY LAW, STATUTE, USAGE OF TRADE OR COURSE OF DEALING. Copyright © 2014 DuPont or its affiliates. All Rights Reserved. The DuPont Oval Logo, DuPont™, The miracles of science™ and all products denoted with ® or ™ are registered trademarks or trademarks of E.I. du Pont de Nemours and Company or its affiliated companies. Common cold is one of the most ubiquitous disease s world wide. Rhinoviruses alone cause approximately half of all the colds, with influenza and coronaviruses having less occurrence and more seasonal impact. Clearly, colds have an impact on the health and quality of life of individuals and families, but also cause major burden on health care costs and missed work days. Probiotics could offer health benefits by stimulating immunity. In a preceding clinical study it was shown that probiotic Bifidobacterium lactis Bl-04 TM reduced the risk of upper respiratory illness episodes in healthy active adults by 27 % (West et al. 2014 Clin Nutr). To objective was to study the effect of B.lactis Bl-04 TM (HOWARU ® Protect Adult) on immune response, rhinovirus shedding and symptoms during experimental rhinovirus infection. A randomized, double blind, placebo controlled clinical trial was conducted in healthy adults at the University of Virginia, USA. Hundred and ninety subjects were randomized 1:1 to treatment and 115 were analyzed for efficacy parameters. Fig 2. The primary outcome of the study was to evaluate inflammatory response (IL-8) in the nasal washes. Probiotic supplementation reduced the post-infectious IL-8 response over 5 days (p=0.027) relative to day 0 (baseline). Ronald B. Turner, MD 2 ; Lotta Stenman, PhD 1 ; Sampo Lahtinen, PhD 1 ; Markus J. Lehtinen, PhD 1 STUDY OUTLINE AND RESULTS Day -28 before infection d0 B. lactis Bl-04TM supplementation (d-28 to d4) Rhinovirus infection at d0 Sampling Symptom questionnaire Nasal wash Nasal washes Blood for Ab test d21 d1 d2 d3 d4 d5 P robio t ic P lacebo 0 50 100 150 Geometric mean IL-8 levels loge[pg/mL] p = 0.042 Probiotic Placebo P robio t ic P lacebo 0 20 40 60 80 100 Subjects that virus was detected from (%) 76 % 91 % p = 0.042 1 2 3 4 5 0 20 40 60 Day Geometric mean rhinovirus titer load (IU/ml) Probiotic Placebo Nasal Inflammatory response during the infection Fig 1. The study subjects consumed probiotic for 28 days before rhinovirus infection was given at day 0. Nasal washes and symptom questionnaires were collected. Proportion of subjects shedding the virus and titer in nasal washes Fig 4. The presence of rhinovirus in nasal washes was analyzed. A. Bl-04 TM decreased the proportion of subjects with detectable rhinovirus (p=0.04) B. In an ad-hoc analysis Bl-04 TM supplementation had a significant effect (p=0.026) on viral load in nasal washes over 5 days Fig 3. After 28 days of Bl-04 TM supplementation, IL-8 concentration in nasal washes was significantly higher in probiotic group at day 0 (baseline before infection) (p=0.042). CONCLUSIONS This study showed that B.lactis Bl-04 TM supplementation had an impact on the innate IL-8 response in the experimental rhinovirus model. Bl-04 TM reduced the amount of virus in the nasal washes and the proportion of subjects with detectable amount of rhinovirus. There were no differences in antibody response or symptom score between the groups. The results indicate that Bl-04 TM may modulate innate immune response against the rhinovirus in humans and have an impact on the viral shedding. 2 University of Virginia School of Medicine Charlottesville Virginia, United States Impact of probiotic on nasal inflammatory response 1 2 3 4 5 0 1 2 3 4 5 Day after infection Ratio of geometric mean IL-8 concentrations Probiotic Placebo

Effect of Probiotic B.lactis Bl-04TM on Innate and Adaptive Host Responses to Experimental Rhinovirus Infection

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Page 1: Effect of Probiotic B.lactis Bl-04TM on Innate and Adaptive Host Responses to Experimental Rhinovirus Infection

BACKGROUND

OBJECTIVE

Effect of Probiotic B.lactis Bl-04TM on Innate and Adaptive Host Responses to Experimental Rhinovirus Infection

1DuPont Nutrition & HealthActive NutritionSokeritehtaantie 2002460 KANTVIK, FINLANDE-mail: [email protected]

The information contained herein is based on data known to DuPont or its affiliates at the time of preparation of the information and believed by them to be reliable. This is business-to-business information intended for food, beverage and supplement producers, and is not intended for the final consumer of a finished food, beverage or supplement product. The information is provided “as is” and its use is at the recipient’s sole discretion and risk. It is the recipient’s sole responsibility to determine the suitability and legality of its proposed use of DuPont products for its specific purposes. Information and statements herein shall not be construed as licenses to practice, or recommendations to infringe, any patents or other intellectual property rights of DuPont or others. DUPONT HEREBY EXPRESSLY DISCLAIMS (I) ANY AND ALL LIABILITY IN CONNECTION WITH SUCH INFORMATION, INCLUDING, BUT NOT LIMITED TO, ANY LIABILITY RELATING TO THE ACCURACY, COMPLETENESS, OR USEFULNESS OF SUCH INFORMATION, AND (II) ANY AND ALL REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO SUCH INFORMATION, OR ANY PART THEREOF, INCLUDING ALL REPRESENTATIONS AND WARRANTIES OF TITLE, NONINFRINGEMENT OF COPYRIGHT OR PATENT RIGHTS OF OTHERS, MERCHANTABILITY, FITNESS OR SUITABILITY FOR ANY PURPOSE, AND WARRANTIES ARISING BY LAW, STATUTE, USAGE OF TRADE OR COURSE OF DEALING.

Copyright © 2014 DuPont or its affiliates. All Rights Reserved. The DuPont Oval Logo, DuPont™, The miracles of science™ and all products denoted with ® or ™ are registered trademarks or trademarks of E.I. du Pont de Nemours and Company or its affiliated companies.

Common cold is one of the most ubiquitous disease s world wide. Rhinoviruses alone cause approximately half of all the colds, with influenza and coronaviruses having less occurrence and more seasonal impact. Clearly, colds have an impact on the health and quality of life of individuals and families, but also cause major burden on health care costs and missed work days. Probiotics could offer health benefits by stimulating immunity. In a preceding clinical study it was shown that probiotic Bifidobacterium lactis Bl-04TM reduced the risk of upper respiratory illness episodes in healthy active adults by 27 % (West et al. 2014 Clin Nutr).

To objective was to study the effect of B.lactis Bl-04TM (HOWARU® Protect Adult) on immune response, rhinovirus shedding and symptoms during experimental rhinovirus infection. A randomized, double blind, placebo controlled clinical trial was conducted in healthy adults at the University of Virginia, USA. Hundred and ninety subjects were randomized 1:1 to treatment and 115 were analyzed for efficacy parameters.

Fig 2. The primary outcome of the study was to evaluate inflammatory response (IL-8) in the nasal washes. Probiotic supplementation reduced the post-infectious IL-8 response over 5 days (p=0.027) relative to day 0 (baseline).

Ronald B. Turner, MD2; Lotta Stenman, PhD1; Sampo Lahtinen, PhD1; Markus J. Lehtinen, PhD1

STUDY OUTLINE AND RESULTS

Day -28 before infection d0

B. lactis Bl-04TM supplementation (d-28 to d4)

Rhinovirus infection at d0

Sampling

Symptomquestionnaire

Nasal wash Nasal washes Bloodfor Abtest

d21d1 d2 d3 d4 d5

Probiotic

Placeb

o0

50

100

150

Geo

met

ricm

ean

IL-8

leve

lslo

ge[p

g/m

L] p = 0.042

ProbioticPlacebo

Probiotic

Placeb

o0

20

40

60

80

100

Subj

ects

that

viru

sw

asde

tect

edfr

om(%

)

76 % 91 %

p = 0.042

1 2 3 4 50

20

40

60

Day

Geo

met

ricm

ean

rhin

oviru

stit

erlo

ad(IU

/ml)

Probiotic

Placebo

Nasal Inflammatory response during the infection

Fig 1. The study subjects consumed probiotic for 28 days before rhinovirus infection was given at day 0. Nasal washes and symptom questionnaires were collected.

Proportion of subjects shedding the virus and titer innasal washes

Fig 4. The presence of rhinovirus in nasal washes was analyzed. A. Bl-04TM decreased the proportion of subjects with detectable rhinovirus (p=0.04) B. In an ad-hoc analysis Bl-04TM supplementation had a significant effect (p=0.026) on viral load in nasal washes over 5 days

Fig 3. After 28 days of Bl-04TM supplementation, IL-8 concentration in nasal washes was significantly higher in probiotic group at day 0 (baseline before infection) (p=0.042).

CONCLUSIONSThis study showed that B.lactis Bl-04TM supplementation had an impact on the innate IL-8 response in the experimental rhinovirus model. Bl-04TM reduced the amount of virus in the nasal washes and the proportion of subjects with detectable amount of rhinovirus. There were no differences in antibody response or symptom score between the groups. The results indicate that Bl-04TM may modulate innate immune response against the rhinovirus in humans and have an impact on the viral shedding.

2University of Virginia School of MedicineCharlottesvilleVirginia, United States

Impact of probiotic on nasal inflammatory response

1 2 3 4 50

1

2

3

4

5

Day after infection

Rat

ioof

geom

etric

mea

nIL

-8co

ncen

trat

ions

ProbioticPlacebo