DOCUMENTEDPROBIOTIC STRAIN.DEDICATED TO HEARTY KIDS.

B. lactis LAFTI® B94

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This is business-to-business information not intended for the health professional and final consumer communications. It is based on our own research and development work and is, to the best of our knowledge, reliable. However, Lallemand does not assume any liability resulting from the use of its products, as conditions of use are beyond our control. The information provided should not be used as a substitute for any form of advice and in all cases, local marketers and distributors should check local regulatory requirements before use as different claims may be approved depending on the regulations applicable in each country. Lallemand does not assume any liability resulting from the claims made by its customers on their packaging or promotional material.

FOR MORE INFORMATION, PLEASE CONTACT: healthsolutions@lallemand.com or www.lallemand-health-solutions.com

White paper

Health claimsNatural and Non-prescription Health Products Directorate (NNHPD), the regulatory agency for natural health products in Canada, has approved health claims for B. lactis LAFTI® B94, such as:

• Helps support intestinal/gastrointestinal health (ages 2 months and older)

• Could promote a favorable gut flora (ages 2 months and older)

• Participates in a healthy microflora balance (ages 2 months and older)

• Helps to relieve abdominal discomfort, such as bloating and constipation (ages 4 years and above)

• Helps children and adolescents with bloating and constipation in irritable bowel syndrome (IBS) (ages 4 years and above)

B. lactis LAFTI® B94

ReferencesBasturk A. et al., 2016. Efficacy of synbiotic, probiotic, and prebiotic treatments for irritable bowel syndrome in children: A randomized controlled trial. Turk J Gastroenterol. 2016;

27: 439-43. Borowitz SM, Cox DJ, Kovatchev B, Ritterband LM, Sheen J, Sutphen J. Treatment of childhood constipation by primary care physicians: efficacy and predictors of

outcome. Pediatrics. 2005 Apr;115(4):873-7. Braegger C, Chmielewska A, Decsi T, et al. Supplementation of infant formula with probiotics and/or prebiotics: A systematic review

and comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr 2011; 52: 238-50. Crittenden R. et al., 2005. Probiotic research in Australia, New Zealand and

the Asia-Pacific region. Current Pharmaceutical Design. 11, 37-53. Crittenden RG et al. Selection of a bifidobacterium strain to complement resistant starch in a synbiotic yoghurt.

Journal of Applied. Microbiology 90 (2001) : 268-278. Dilli et al., 2013, Treatment outcomes of infants with Cyanotic Congenital Heart Disease treated with symbiotics, Pediatrics,

0031-4005. Dilli et al., 2015, The ProPre-save study: effects of probiotics and prebiotics alone or combined on Nectrotizing enterocolitis in very low birth weight infants, The Journal

of Pediatrics 2015. Erdogan et al., 2012, The comparition of the efficacy of two different probiotics in rotavirus gastroenteritis in children, Journal of Tropical Medicine, Volume

2012, Article ID 787240. Gibson G. R. et al., 2017. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of

prebiotics. Nat Rev Gastroenterol Hepatol. 2017.75. Işlek et al., 2014, The role of Bifidobacterium lactis B94 plus inulin in the treatment of acute infectious diarrhea in children, Turk

J Gastroenterol 2014; 25: 628-33. Koletzko S, Osterrieder S. Acute infectious diarrhea in children. Dtsch Arzetbl Int 2009; 106: 539-47. 2. Mahoney M, Henriksson A. The effect

of processed meat and meat starter cultures on gastrointestinal colonization and virulence of Listeria monocytogenes in mice. International Journal of Food Microbiology 84 (2003)

255– 261. Osemene (2015) Irritable Bowel Syndrome in Children and Adolescents, US Pharmacist 40(5):46-50. Pang G. 2005. A comparative study of probiotic bacterial strains in

vitro and in vivo. School of Biomedical Sciences, University of Newcastle,NSW (Internal Report). Peran L. et al. 2007. A comparative study of the preventative effects exerted by three

probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis. Journal Of Applied Microbiology 103; 836–844. Sandhu BK, Paul

SP. Irritable bowel syndrome in children: pathogenesis, diagnosis and evidence-based treatment. World J Gastroenterol. 2014 May 28;20(20):6013-23. Su P, Henriksson A, Tandianus

JE, Park JH, Foong F, Dunn NW. Detection and quantification of Bifidobacterium lactis LAFTI® B94 in human faecal samples from a consumption trial. FEMS Microbiol Lett. 2005 Mar

1;244(1):99- 103. Su P., Henriksson A. and Mitchell H. Prebiotics enhance survival and prolong the retention period of specific probiotic inocula in an in vivo murine model. Journal

of Applied Microbiology 103 (2007): 2392–2400. Van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol.

2006 Oct;101(10):2401-9. Walker CL, Rudan I, Liu L, et al. Global burden of childhood pneumonia and diarrhoea. Lancet 2013; 20; 381: 1405-16. WebMD. Abdominal Pain,

Age 11 and Younger - Topic Overview. Zhang L., Su P., Henriksson A., O’Rourke J. and Hazel Mitchell. (2008 ) Investigation of the Immunomodulatory Effects of Lactobacillus casei

and Bifidobacterium lactis on Helicobacter pylori Infection. Blackwell Publishing Ltd, Helicobacter 13: 183–190.

Available in various dosage forms:

- Powders or orodispersible powders

- Sticks or sachets

- Capsules or sprinkle caps

- Chewable tablets

The probiotic strain Bifidobacterium lactis LAFTI® B94 has been specifically documented in the area of gut health. It benefits from a strong body of clinical evidence in children and adolescents, supported by in vitro and in vivo documentation of its modes of action.

B. lactis LAFTI® B94

32

A first-class probiotic strain FOR HEARTY KIDS AND TEENS

B. lactis LAFTI® B94 AND INULIN, THE SYNBIOTIC EFFECT

KEY PROBIOTIC FEATURES

• Survival through the digestive tract: in vitro human stomach model shows survival within the stomach environment and physiological concentration of bile [Crittenden, 2001]. This was further confirmed by a study in adult volunteers. Four weeks after the feeding stopped, B. lactis LAFTI® B94 could still be detected in one subject [Su, 2005] (Fig. 1).

• Competition with other microorganisms such as Helicobacter pylori, Salmonella typhimurium or Listeria monocytogenes (demonstrated in animal models) [Zhang, 2008; Crittenden, 2005; Mahoney, 2003].

• Support of natural defenses, in both in vitro and in vivo models of immune challenges: B. lactis LAFTI® B94 has been shown to reduce the production of TNF-α, iNOS and COX-2 [Peran, 2007], increase the level of Interleukin 12 and decrease the eosinophils level [Pang, 2005].

Further to its selection, the strain was fully identified by genetic methods and its genome sequenced.

1 7 14 21 28 36

LAFT

I® B

94Lo

g 10

CFU

/g w

et w

eigh

t

Feeding period (day 1-7), washout period (day 8-35)

10

7.5

5

2,5

0

Subject 1Subject 2Subject 3Subject 4Subject 5

B. lactis LAFTI® B94 has been selected and fully documented for its probiotic features in in vitro and in vivo testing:

Figure 1: Gastrointestinal tract survival of B. lactis LAFTI® B94 in consumption trial faecal samples

B. lactis LAFTI® B94

A CONVERGING BODY OF CLINICAL EVIDENCE

Gut transit in children & teens

1 clinical study on occasional constipation in children and teenagers [Basturk, 2016]

Gut health in infants & children

2 clinical studies on occasional diarrhea in infants and children [Erdogan, 2012], [Islek, 2014]

2 clinical studies in premature infants at risk for Necrotizing Enterocolitis (NEC) [Dilli, 2013], [Dilli, 2015]

FOR OTHER USE THAN FOOD/DIETARY SUPPLEMENT

Log

10 C

FU/g

wet

wei

ght

0 50 100 150 200

Time (h)

10

9

8

7

6

5

4

FOSInulinSOS Glucose

Figure 2: Detection of B. lactis LAFTI® B94in faecal samples from mice

Prebiotics are defined as “a substrate that is selectively utilized by host microorganisms conferring a health benefit” [Gibson, 2017], in other words a “food for probiotic”. Most commonly used natural prebiotics are: inulin, fructo- oligosaccharides (FOS) or galacto-oligosaccharides (GOS). Their overall benefits could include normal bowel function and management of occasional constipation. The effects of prebiotics have been extensively investigated in infant nutrition studies. In particular, it has been shown that stool properties of infants receiving prebiotics are similar to those of breastfed infants [Braegger, 2011].

In an in vitro study, B. lactis LAFTI® B94 was first selected among 40 Bifidobacterium isolates for its capacity to hydrolyze resistant starch, grow on various prebiotic substrates and resist to acidic and protease- rich environment of stomach and physiological concentration of bile. A selection of prebiotics was then screened for their potential synergy with B. lactis LAFTI® B94. Most of them showed positive effect on the growth of B. lactis LAFTI® B94 in vitro (inulin, FOS, GOS, isomalto-oligosaccharides, xylo-oligosaccharides, and soybean-oligosaccharides) [Crittenden, 2001].

Prebiotics were further tested in vivo (mice model) [Su, 2007], indicating that FOS and inulin were the best candidates to increase the survival and retention time of the probiotic B. lactis LAFTI® B94 in the gut, compared to control (glucose). Both extended the retention time of B. lactis LAFTI® B94 from 3 to around 10 days (fig. 2).

Based on these data, inulin has been used in the formulation of children specific synbiotic formula in association with B. lactis LAFTI® B94 (5x109 CFU B. lactis LAFTI® B94 and 900 mg inulin per sachet). Most of the randomized trials presented use this formulation. Inulin is a long-chain fructo-oligosaccharide (FOS) obtained from chicory extract. Its consumption has been linked to increased levels of bifidobacteria and lactobacilli in the intestinal flora.

Gut health is a common concern in children and adolescents. Gut discomfort, such as occasional bloating, irregular transit and constipation, is very frequent in young populations and often represents a reason to visit the doctor. About 1 out of 3 children is seen by a doctor for abdominal discomfort by the time they are aged 15, however the majority has no serious health problems [WebMD].

54

Kids’ & teens’ DIGESTIVE COMFORT

B. lactis LAFTI® B94 SIGNIFICANTLY IMPROVES BLOATING, BELCHING–ABDOMINAL FULLNESS AND OCCASIONAL CONSTIPATION IN CHILDREN AND TEENS [BASTURK, 2016]

A MATTER OF BALANCE

Most of gut health issues can be linked to stress factors for the gut microbiota - dietary changes, stress, antibiotic, poor diet balance etc. - which can affect its composition and balance. In children, the gut microbiota and immune systems are still maturing. The role of probiotics in preserving and restoring the gut microbiota and reinforcing the body natural defenses is well documented. With their track record of safety, biological image and lack of side-effects, probiotics are particularly well suited for children’s gut health management.

GUT DISCOMFORT IN CHILDREN AND TEENAGERS

• Occasional constipation has been described as the most common gut disturbance in young children, with reported prevalence between 1% and 30% [Van Den Berg, 2006]. It is the major reason for 35% of visits to pediatric gastroenterologists [Borowitz, 2005]. Most cases are temporary, and can often be linked to behavioral causes (early toilet training in the youngest) or dietary changes.

• Overall occasional abdominal discomfort concerns 8% to 17% of children and 13% to 38% of adolescents, with higher prevalence in girls [Osemene, 2015]. Gut disturbances may be associated with a brain-gut axis disorder. It is linked with occasional discomfort in daily life, with possible impact on feeling healthy, sleeping behavior, stress and overall quality of life. It can impact school attendance and success, which in turns generates still more stress.

Children and teens experiencingoverall occasional abdominaldiscomfort in % [Osemene, 2015]

13% to 38%

Teens

Kids

8% to 17%

Kids

71 children and adolescents, aged 4-16 years old, were enrolled in a randomized, double-blind, controlled study [Basturk, 2016]. They were randomized between 3 groups:

• PREBIOTIC: the children received 900 mg of inulin/day for 4 weeks.

• PROBIOTIC: the children received 5x109 CFU B. lactis LAFTI® B94/day for 4 weeks.

• SYNBIOTIC: the children received 900 mg of inulin + 5x109 CFU B. lactis LAFTI® B94/day for 4 weeks.

At the end of the 4-week period, the following parameters were monitored for all children: • postprandial swelling, • belching-abdominal distension, • mucoid defecation, • difficulty in defecation, • feeling of incomplete defecation, • urgent defecation.

In summary, the results of the study showed that B. lactis LAFTI® B94 alone significantly improved symptoms of gut discomfort (fig. 3): bloating after meals (p=0.016), belching–abdominal fullness (p<0.001) and constipation (p=0.031).

In addition, the synbiotic supplement also improved a fourth symptom: the presence of mucus in the feces (p=0.021) (fig. 3).

Altogether, the synbiotic group showed recovery from all measured primary parameters of the study in 39.1% of patients and the probiotic alone in 29.2%. There was a significant difference between the prebiotic and synbiotic groups. No side effects (diarrhea, constipation, abdominal pain) were observed in any children.

% of participants before and after 1 month of probiotic or synbiotic intake

PROBIOTIC group

Bloating after meals

Belching-abdominal fullness

Difficulty with defecation

* p=0.016

* p<0.001

* p=0.031

BeforeAfter 1 month

75

75

70.8

45*

25*

45.8*

0 20 40 60 80

SYNBIOTIC group

Bloating after meals

Belching-abdominal fullness

Difficulty with defecation

Mucus in stool

* p =0.004

* p <0.001

* p =0.021

* p =0.021

BeforeAfter 1 month

69.6

65.2

56.5

52.2

30.4*

13*

21.7*

17.4*

0 20 40 60 80

B. lactis LAFTI® B94

Figure 3: B. lactis LAFTI® B94 (with or without inulin) and occasional gut discomfort

76

Gut health IN INFANTS & CHILDREN

B. lactis LAFTI® B94 + INULIN & DURATION OF OCCASIONAL DIARRHEA [Islek, 2014]

Another randomized, placebo controlled trial involved 156 children with occasional diarrhea, aged 2 months to 5 years [Islek, 2014]. They received either placebo or synbiotic supplement containing 5x109 CFU B. lactis LAFTI® B94 and 900 mg inulin, once a day for 5 days, in addition to normal fluid therapy and nutritional support. The synbiotic significantly reduced the duration of occasional diarrhea by 31 hours on average vs placebo (p<0.001) (fig. 5). Moreover, it appears that the synbiotic was more effective when taken within the first 24 hours of diarrhea (p=0.002).

Occasional diarrhea of various origins is particularly frequent in young children. Worldwide, 1 to 1.5 million children are affected every year. 80% of them are under two years of age and most are 6-11 month-old infants. Children under the age of five experience occasional diarrhea 3 to 4 times per year, and very few (1%-3%) of these cases are serious [Koletzko, 2009; Walker, 2013].

B. lactis LAFTI® B94 & DURATION OF OCCASIONAL DIARRHEA [Erdogan, 2012]

A randomized, placebo controlled trial was conducted in 75 children aged 5 months to 5 years, with occasional diarrhea [Erdogan, 2012]. The probiotic was supplemented daily at 5x109 CFU in combination with oral rehydration therapy and rapid refeeding with a normal diet. B. lactis LAFTI® B94 significantly reduced the duration of occasional diarrhea by approximately 3 days vs placebo (p<0.001) (fig. 4).

Figure 4: Duration time (days) of occasional diarrhea

B. lactis LAFTI® B94

Figure 5: Duration time (days) of occasional diarrhea

8

6

4

2

0Control LAFTI® B94

*p<0.001

7

4.1

Day

s

*p<0.001

FOR OTHER USE THAN FOOD/DIETARY SUPPLEMENT

In neonates, more critical gut disorders such as necrotizing enterocolitis (NEC) can appear. It may result from an inappropriate immunologic response to intestinal bacteria and a disruption in the balance of the gastrointestinal microbiota in susceptible individuals.

Two randomized controlled trials have been performed in infants at risk for NEC*. B. lactis LAFTI® B94 with inulin decreases the risk of either nosocomial infections [Dilli, 2013 - study conducted on 100 hospitalized neonates], or NEC [Dilli, 2015 - study conducted on 400 hospitalized infants with very low birth weight] in those at-risk populations.

* Such studies in hospitalized infants are to be taken with caution. In these conditions, probiotics must be considered as pharmaceuticals and used under medical supervision. However, the studies serve as a real proof of concept about the benefits of B. lactis LAFTI® B94 for gut health in young populations.

6

4

2

0

- 31h

Day

s

Control

5.2

LAFTI® B94 + inulin

3.9

DOCUMENTEDPROBIOTIC STRAIN.DEDICATED TO HEARTY KIDS.

B. lactis LAFTI® B94

PR

O 2

46 -

201

803

- ©

shut

ters

tock

- G

raph

ic d

esig

n: la

uren

cebo

nhom

me.

com

This is business-to-business information not intended for the health professional and final consumer communications. It is based on our own research and development work and is, to the best of our knowledge, reliable. However, Lallemand does not assume any liability resulting from the use of its products, as conditions of use are beyond our control. The information provided should not be used as a substitute for any form of advice and in all cases, local marketers and distributors should check local regulatory requirements before use as different claims may be approved depending on the regulations applicable in each country. Lallemand does not assume any liability resulting from the claims made by its customers on their packaging or promotional material.

FOR MORE INFORMATION, PLEASE CONTACT: healthsolutions@lallemand.com or www.lallemand-health-solutions.com

White paper

Health claimsNatural and Non-prescription Health Products Directorate (NNHPD), the regulatory agency for natural health products in Canada, has approved health claims for B. lactis LAFTI® B94, such as:

• Helps support intestinal/gastrointestinal health (ages 2 months and older)

• Could promote a favorable gut flora (ages 2 months and older)

• Participates in a healthy microflora balance (ages 2 months and older)

• Helps to relieve abdominal discomfort, such as bloating and constipation (ages 4 years and above)

• Helps children and adolescents with bloating and constipation in irritable bowel syndrome (IBS) (ages 4 years and above)

B. lactis LAFTI® B94

ReferencesBasturk A. et al., 2016. Efficacy of synbiotic, probiotic, and prebiotic treatments for irritable bowel syndrome in children: A randomized controlled trial. Turk J Gastroenterol. 2016;

27: 439-43. Borowitz SM, Cox DJ, Kovatchev B, Ritterband LM, Sheen J, Sutphen J. Treatment of childhood constipation by primary care physicians: efficacy and predictors of

outcome. Pediatrics. 2005 Apr;115(4):873-7. Braegger C, Chmielewska A, Decsi T, et al. Supplementation of infant formula with probiotics and/or prebiotics: A systematic review

and comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr 2011; 52: 238-50. Crittenden R. et al., 2005. Probiotic research in Australia, New Zealand and

the Asia-Pacific region. Current Pharmaceutical Design. 11, 37-53. Crittenden RG et al. Selection of a bifidobacterium strain to complement resistant starch in a synbiotic yoghurt.

Journal of Applied. Microbiology 90 (2001) : 268-278. Dilli et al., 2013, Treatment outcomes of infants with Cyanotic Congenital Heart Disease treated with symbiotics, Pediatrics,

0031-4005. Dilli et al., 2015, The ProPre-save study: effects of probiotics and prebiotics alone or combined on Nectrotizing enterocolitis in very low birth weight infants, The Journal

of Pediatrics 2015. Erdogan et al., 2012, The comparition of the efficacy of two different probiotics in rotavirus gastroenteritis in children, Journal of Tropical Medicine, Volume

2012, Article ID 787240. Gibson G. R. et al., 2017. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of

prebiotics. Nat Rev Gastroenterol Hepatol. 2017.75. Işlek et al., 2014, The role of Bifidobacterium lactis B94 plus inulin in the treatment of acute infectious diarrhea in children, Turk

J Gastroenterol 2014; 25: 628-33. Koletzko S, Osterrieder S. Acute infectious diarrhea in children. Dtsch Arzetbl Int 2009; 106: 539-47. 2. Mahoney M, Henriksson A. The effect

of processed meat and meat starter cultures on gastrointestinal colonization and virulence of Listeria monocytogenes in mice. International Journal of Food Microbiology 84 (2003)

255– 261. Osemene (2015) Irritable Bowel Syndrome in Children and Adolescents, US Pharmacist 40(5):46-50. Pang G. 2005. A comparative study of probiotic bacterial strains in

vitro and in vivo. School of Biomedical Sciences, University of Newcastle,NSW (Internal Report). Peran L. et al. 2007. A comparative study of the preventative effects exerted by three

probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis. Journal Of Applied Microbiology 103; 836–844. Sandhu BK, Paul

SP. Irritable bowel syndrome in children: pathogenesis, diagnosis and evidence-based treatment. World J Gastroenterol. 2014 May 28;20(20):6013-23. Su P, Henriksson A, Tandianus

JE, Park JH, Foong F, Dunn NW. Detection and quantification of Bifidobacterium lactis LAFTI® B94 in human faecal samples from a consumption trial. FEMS Microbiol Lett. 2005 Mar

1;244(1):99- 103. Su P., Henriksson A. and Mitchell H. Prebiotics enhance survival and prolong the retention period of specific probiotic inocula in an in vivo murine model. Journal

of Applied Microbiology 103 (2007): 2392–2400. Van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol.

2006 Oct;101(10):2401-9. Walker CL, Rudan I, Liu L, et al. Global burden of childhood pneumonia and diarrhoea. Lancet 2013; 20; 381: 1405-16. WebMD. Abdominal Pain,

Age 11 and Younger - Topic Overview. Zhang L., Su P., Henriksson A., O’Rourke J. and Hazel Mitchell. (2008 ) Investigation of the Immunomodulatory Effects of Lactobacillus casei

and Bifidobacterium lactis on Helicobacter pylori Infection. Blackwell Publishing Ltd, Helicobacter 13: 183–190.

Available in various dosage forms:

- Powders or orodispersible powders

- Sticks or sachets

- Capsules or sprinkle caps

- Chewable tablets