probio sap-90 - nfh property of institut rosell/lallemand for professional use only • not intended...

ProBio SAP-90

1. The Intestinal Microflora

2. ProBio SAP-90

3. Probiotics Characterization: In Vitro

4. Health Benefits

Cont

ents

Property of Institut Rosell/LallemandFor professional use only • Not intended for customers

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One to two days after birth, a specific microflora colonizes the gastrointestinal tract, organized in populations that remain balanced along the GI tract. This microflora is divided into 3 groups:

• The main flora composed of Bifidibacterium and Bacteroides• The secondary flora composed of Lactobacillus• The transitory flora, potentially pathogenic

Approximately 100 000 billion bacteria representing more than 400 different species reside in the digestive tract. This means we have 10 times more bacteria than human cells in our body. Most bacteria are localized in the colon. The stomach flora is very poor as the acidity is too high to allow bacteria to grow. The concentration of bacteria increases in the small intestine and further increases in the colon.

This endogenous microflora exerts 2 main positive functions. Involved in the digestion process, it also protects the host against infections. However, it may play a role in the development of intestinal diseases such as inflammatory bowel disease and cancer.

Moreover, in spite of its stability, the intestinal microflora can be affected by a variety of factors. Host factors, such as gastric acid, bile salts, and mucus in the intestinal wall can affect the composition of the microflora. In addition, diet, medication, infections, stress, ageing, and climate can alter the microflora(1, 2, 3). Consumption of live microorganisms (probiotics) modulates the endogenous flora in a positive way.

There are 2 main groups of probiotic bacteria:

Lactic acid bacteriaThe lactic acid bacteria produce lactic acid and are divided into two categories:

• bacillus (ex. Lactobacillus acidophilus ssp. helveticus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus bulgaricus)

• cocci (ex. Streptococcus thermophilus, Lactococcus lactis, Enterococcus faecium)

BifidobacteriaBifidobacteria produce both lactic and acetic acid. With age, the concentration of bifidobacteria decreases and species change (ex. Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium breve, Bifidobacterium bifidum).

1. The intestinal microflora


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FormProBio SAP-90, size 2 enteric-coated capsule, contains a specific blend of 10 probiotic bacteria.

Ingredients per capsuleProbiotic bacteria: 11 billion

• Lb. rhamnosus B Rosell-1049: 40.0%• Lb. rhamnosus A Rosell-11: 35.5%• Lb. acidophilus ssp. helveticus Rosell-52: 5.0%• Lb. plantarum Rosell-202: 4.0 %• Lb. casei Rosell-256: 4.0%• Bf. longum Rosell-175: 3.0%• Bf. infantis Rosell-33: 3.0%• Bf. breve Rosell-70: 3.0%• Sc. thermophilus: 2.0%• Lb. delb. ssp. bulgaricus: 0.5%

Ascorbic acid 0.4%

Other ingredients: Fructo-oligosaccharides (FOS) Inulin, Arabino-oligosaccharides (AOS), magnesium stearate (vegetable source), ascorbic acid, ultra dry maltodextrin, in enteric coated vegetable capsules.Water based enteric coating (hydroxypropylmethylcellulose, magnesium silicate, methacrylate copolymer).

Recommended useAdults

1 to 2 capsules per day. Can be taken at any time of the day.Storage

ProBio SAP-90 should be stored in a dry and cool place (4 °C).

2. ProBio SAP-90


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3. Probiotics characterization: in vitroMicroorganisms chosen to be incorporated in probiotic preparations should remain alive until they reach the intestine. In order to do so, they have to pass through the gastrointestinal tract alive. Evaluation of their resistance to stomach acidity and biliary salts are pertinent criteria for probiotic selection. These tests can be performed in vitro.

Resistance to acidityOne of the body’s physiological mechanisms to fight against foreign microorganisms is the fact that the stomach’s pH is very low and the majority of microorganisms cannot survive in such an acidic environment.

Probiotic resistance to acidity has been tested in vitro. Each strain has been diluted in water at pH 4 and pH 3, for 30 minutes at 37°C, which represents the average amount of time they stay in the stomach during digestion (figure 1).

Survival rate after 30 min at pH 4

Survival rate after 30 min at pH 3

Surv

ival

rate

Surv

ival

rate

L. acidophilus ssp. helveticus

Rosell-52

L. acidophilus ssp. helveticus

Rosell-52

120%

Fig. 1Survival of probiotic strains at pH 4

Fig. 2Survival of probiotic strains at pH 3

L. rhamnosus Rosell-11


L. casei Rosell-256

L. casei Rosell-256

L. plantarum Rosell-202


B. breve Rosell-70

B. breve Rosell-70

B. longumRosell-175

B. longumRosell-175

100%

100%

80%

80%

60%

60%

40%

40%

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20%

0%

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As can be seen, probiotic strains are not equivalent with regard to their resistance to gastric acidity. Most probiotics in the market are sensitive to gastric acidity and that’s why it is recommended to consume them during meals. As a matter of fact, stomach pH varies during the day, as a function of the buffering capacity of food, and is higher during digestion, as shown in figure 3 below.

Institut Rosell/Lallemand has developed a new technology to increase the resistance of probiotics to the stomachs harsh conditions. SAC5, Safe Aqueous Coating that allows the capsule to stay intact in the stomach and thus allows probiotics to remain alive in the stomach (see figure 4).

SAC5, water based enteric coating, permits an opening of the capsule at intestinal pH (over 5.5). Probiotics are then released alive directly in the portion of the intestine where they act (see figure 5).

Surv

ival

rate

120%

Fig. 3pH variation in the stomach during the daytime

100%

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0%

Fig. 4Survival rate of probiotics at stomach pH with and without SAC5 protection

pH variation in the stomach during the daytime

pH

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8 9 10 11 12 13 14 15 16 17

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5

4

3

2

1

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Day time

Survival rate of Rosell probiotic bacteria with and without SAC5 protection, 30 min at pH 2

Rosell-11 SAC5Rosell-11Rosell521 SAC5Rosell-52

Strains


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Resistance to bileBile secretion is one of the body’s physiological mechanisms to fight against foreign microorganisms. The ability of lactic bacteria to develop in the presence of bile, even with slower kinetic growth, is one of the factors favorable to the development of lactic bacteria in vivo. This primarily occurs in the large intestine.

Results show that bile has an inhibitory effect on the growth of each probiotic bacteria. However, while acidity can be lethal for probiotics, they are intrinsically resistant to bile salts which only exert an inhibitory effect on their growth. Thus, probiotic bacteria are able to survive in high concentrations of bile and should, in vivo, reach the distal end of the small intestine without damage.

SAC5 capsules resistance and dissolution to variation in acidity

Probiotic’s bile sensitivity: inhibition of growth rate

Diss

olut

ion

Perc

enta

ge o

f gro

wth

rate

inhi

bitio

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Fig. 5SAC5 resistance at stomach pH and dissolution at intestinal pH

Fig. 6Inhibition of growth rate of different probiotic strains in the presence of 3% bile in their growth medium

1.2 1.5pH values

Strains

5.5 7.2

B. breve Rosell-70


L. casei Rosell-256


L. acidophilus ssp. helveticus Rosell-52

100%

100%

80%

80%

60%

60%

40%

40%

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20%

0%

0%


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Inhibition of E. coli O127:H6 (at 107 CFU/mL) adhesion to HEp-2 cells by Lactobacilli

% A

dhes

ion

of E

. col

i to

inte

stin

al ce

lls

Fig. 7Adhesion percentage of E. coli O127:H6 to intestinal cells depending on the concentration of L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11

Lb. rhamnosus Rosell-11 Lb. acidophilus ssp. helveticus Rosell-52

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Adhesion to the epitheliumAdhesion of probiotic strains to the intestinal epithelium is another important factor as adhesion allows the probiotics to temporarily colonize the gut. Unfortunately, it is very difficult to measure adherence without doing intestinal tissue biopsies. Therefore, scientists have developed in vitro adherence tests with human cells grown in tissue culture.

The ability of L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 to bind to intestinal epithelial cells (HT-29, CAC0-2) has been determined(4). Both strains have shown very strong adherence capacity to the surface of epithelial cells (refer to the scanning electron photomicrography).

Inhibition of Escherichia coliIn vitro tests have shown that L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 are able to inhibit the adhesion of two types of Escherichia coli to intestinal epithelial cells (T84), in a concentration-dependent manner: enteropathogenic E. coli O127:H6 and enterohaemorrhagic E. coli O157:H7, which both cause diarrhea.

The ability of L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 to inhibit E. coli adhesion did not entirely correlate with their ability to bind intestinal epithelial cells suggesting that there is more than one mechanism of inhibition. Further investigation showed that the inhibition is not mediated by killing the E. coli.

These studies used very high concentrations of E. coli (107 CFU/mL). However, typically in the colon, the concentration of pathogenic E. coli will not be over 102 CFU/mL, thus we should only need to achieve about a 103 or 104 CFU/mL concentration of L. acidophilus ssp. helveticus to inhibit E. coli adhesion(4).

Overall, these results show that both L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 can prevent the adherence of E. coli to intestinal epithelial cells, thus removing a factor that is responsible for 70% of the incidence of traveler’s diarrhea.

120%0 CFU/mL106 CFU/mL108 CFU/mL1010 CFU/mL


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Modulation of immune systemThe intestinal immune system has two, apparently contradictory, but very significant functions for health. Oral tolerance functions to suppress immune responses against foreign proteins (of bacterial or food origins) that are commonly found in the digestive tract. This prevents over-sensitivity to food and minimises chronic digestive tract inflammation, such as occurs in Crohn’s disease. On the other hand, the intestinal immune system must promote protective immune responses against pathogenic microorganisms. Enhancing antibody synthesis is a key component of protective immunity in the gut.

The microbial balance of the intestinal flora affects the immune system’s capacity to respond to ingested pathogens. In light of this, the ability of the Lactobacilli to influence the intestinal immune system has come under scrutiny. For many years, studies have been conducted with different probiotic strains in vitro, in vivo and in animal models, which together suggest that probiotic strains have the ability to modulate the immune system(5).

The intestine is one of the most important lymphoid organs in the body. Its surface area represents about 300 m2. The primary site of action for probiotics is the intestinal wall where they interact with immune cells, either by direct contact or by stimulation of cytokine production (immune cell mediators that facilitate communication and coordination within the immune system).

In vitro studies have shown that both L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 modulate the immune system. These findings suggest that, in vivo, the immune system will react more rapidly and more efficiently against pathogenic microorganisms responsible for intestinal disorders.

L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 increase the number of immune cells ready to fight intestinal pathogens. In fact, L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 have been shown to activate immune cells in vitro. Increased rates of proliferation (indicated by higher optical densities) are a clear indication that L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 stimulate immune cell activation. Higher

Inhibition of E. coli O157:H7 (at 107 CFU/mL) adhesion to HEp-2 cells by Lactobacilli

% A

dhes

ion

of E

. col

i to

inte

stin

al ce

lls

Fig. 8Adhesion percentage of E. coli O157:H7 to intestinal cells depending on the concentration of L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11

Lb. rhamnosus Rosell-11 Lb. acidophilus ssp. helveticus Rosell-52

100%

80%

60%

40%

20%

0%

120%0 CFU/mL106 CFU/mL108 CFU/mL1010 CFU/mL


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concentrations of L. acidophilus ssp. helveticus Rosell-52 and L. rhamnosus A Rosell-11 cause a greater proliferation of immune cells. The end result is a larger and more competent population of immune cells, primed and ready to fight infection. Not all probiotic strains are able to stimulate immune cell proliferation in the same manner. L. rhamnosus A Rosell-11 shows the best effect, followed by L. acidophilus ssp. helveticus Rosell-52. However, L. delbrueckki Rosell-187 seems to be less effective(6).

L. acidophilus ssp. helveticus Rosell-52 stimulates antibody productionIn vitro studies have demonstrated that L. acidophilus ssp. helveticus Rosell-52 stimulates B cells to produce antibodies. B cells produce antibodies that specifically recognize and target a particular pathogen. Normally, B cells only secrete antibodies when they are activated by that pathogen, which means it must be present in the body for an efficient B cell response to occur. However, L. acidophilus ssp. helveticus Rosell-52 has mitogenic effects on B cells, which results in polyclonal B cell activation, and production of a wide spectrum of antibodies that recognize a variety of pathogens. The significance of this finding is that high titres of antibodies are released into the intestinal lumen, ready to attach and begin destruction of all potentially ingested pathogens.

L. acidophilus ssp. helveticus Rosell-52 stimulates production of IgM in a dose dependant manner. IgM is the first antibody produced when antigens challenge the body’s immune system. Most of the IgM produced is not L. acidophilus ssp. helveticus Rosell-52 specific. This indicates that L. acidophilus ssp. helveticus Rosell-52 exerts a mitogenic effect on B cells, stimulating the production of both L. acidophilus ssp. helveticus Rosell-52 specific and non-specific antibodies targeted against potential pathogens. L. acidophilus ssp. helveticus Rosell-52 stimulation of non-specific antibody production by B cells may be one of the primary ways that L. acidophilus ssp. helveticus Rosell-52 exerts its protective effects in the intestine.

L. acidophilus ssp. helveticus Rosell-52 participates in controlled inflammationEven in the absence of inflammatory stimuli from the environment, such as those seen during the pathological consequences of infection, the healthy and mature intestine exists in a proinflammatory state. This provokes many differentiated and activated lymphocytes that generate proinflammatory cytokines, a mechanism that has been called controlled inflammation. Controlled inflammation is vital to health, as it promotes the existence of an active, fast acting immune response to potential pathogens.

All in vitro trials conducted thus far suggest that in vivo, L. acidophilus ssp. helveticus Rosell-52 increases the vigilance of the immune system, strengthening it and allowing it to react more efficiently when confronted with pathogen.

Moreover, L. rhamnosus A Rosell-11 can down-regulate elements of the inflammatory response (cytokines IL-8 and TNF-α), which is an important property in treating and preventing inflammation associated with traveler’s diarrhea.


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4. Health BenefitsHealth benefitsLactobacillus acidophilus ssp. helveticus Rosell-52Lactobacillus acidophilus ssp. helveticus is a natural component of the intestinal and vaginal microflora. As L. acidophilus ssp. helveticus is microaerophilic, it is able to colonize the end of the small intestine and the colon. The species L. acidophilus ssp. helveticus has been well studied and several probiotic effects are reported in the literature: ability to survive in the stomach(7) and to reach the intestine alive, antimicrobial activities against pathogens(8), alleviate symptoms of lactose intolerance(9), reduce the cholesterol level(10), boost the immune system(11).

Several clinical trials have demonstrated the beneficial effect of L. acidophilus ssp. helveticus Rosell-52 together with Rosell-11 in case of lactose intolerance(12), diarrhoea of various origins(13), constipation and bloating(14).

Furthermore, L. acidophilus ssp. helveticus Rosell-52 has been shown in vitro to boost the immune system. As discussed above, L. acidophilus ssp. helveticus Rosell-52 modulates the immune system by inducing immune cell proliferation, by exerting a mitogenic effect on B cells, and by up regulating combinations of cytokines which serve to direct T cell differentiation towards the TH1 type, or cell mediated response(6).

Lactobacillus rhamnosus A Rosell-11Lactobacillus rhamnosus is natural component of the intestinal and vaginal microflora. As L. rhamnosus is microaerophilic, it will colonize the end of the small intestine and the colon. The species L. rhamnosus is one of the most studied in the probiotic world and most of the health benefits of probiotics have been demonstrated with this species.

Rosell-11 is recommended to balance the intestinal microflora thanks to its ability to prevent adherence of E. coli to intestinal epithelial cells, which causes diarrhoea(4). Several clinical trials have demonstrated the beneficial effect of Rosell-11 together with L. acidophilus ssp. helveticus Rosell-52, and together these strains have show efficacy in the alleviation of lactose intolerance(12), diarrhoea of various origins(13), constipation and bloating(14).

Furthermore, Rosell-11 has been shown to boost the immune system in vitro. As discussed above, L. acidophilus ssp. helveticus Rosell-52 modulates the immune system by inducing immune cell proliferation, and functions to upregulate several cytokines, as well as to downregulate other inflammatory cytokines(6).

Lactobacillus casei Rosell-215L. casei strains are naturally found in fermented vegetables, milk, and meat as well as in the human intestine and mouth. It has been recently shown that this lactic acid bacteria is able to alter the composition and some of the functions of the gastrointestinal tract. Although mechanisms for specific actions are not clear, positive results related to the prevention and treatment of diarrhea have been demonstrated. The beneficial effects seem to be associated with L. casei’s ability to alter the activity of the intestinal microflora and to modulate the immune system(15).


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BifidobacteriaThe name Bifidobacteria comes from the observation that these Gram-positive rods often exist in a Y-shaped or “bifid” form. Bifidobacteria are anaerobes with a special metabolic pathway which allows these lactic acid bacteria to produce acetic acid as well lactic acid. They frequently have special nutritional requirements, thus often making these bacteria difficult to isolate and grow in the laboratory.

Quality of food could influence intestinal flora depending if babies are breast-fed or not. It has been demonstrated that Bifidobacteria are in higher concentration in breast-fed infant’s flora than in other infants.

Bifidobacteria have many beneficial health effects. The role of endogenous Bifidobacteria has not been effectively studied at this time but it is well known that the risk of diarrhoea is lower if newborns are exclusively breast-fed as opposed to those fed with infant formulas(16). The higher level of Bifidobacteria is one explanation for this phenomenon.

Bifidobacteria have been reported to be responsible for many different effects: increases stool frequency(17), and decreased transit time(18). Although the mechanism by which Bifidobacteria may alter the intestinal microflora has not been clearly determined, it is possibly related to the production of acetic acid and lactic acid which may restrict the growth of potential pathogenic and putrefactive bacteria(19). That acetic acid is more bacteriostatic than lactic acid at the same pH may explain a greater effect of Bifidobacteria compared to certain other bacteria, such as those found in yogurt, which produce only lactic acid.

It has been established that certain strains of Bifidobacteria, which have been selected for their ability to resist acid digestion and the action of bile salts, survive intestinal transit and reach the colon in significant numbers. These live bacteria have the potential to influence the endogenous intestinal microflora. Altering the endogenous microflora may result in such physiological effects as altering enzyme activities of the microflora, and affecting gut transit.

Bifidobacterium longum Rosell-175B. longum Rosell-175 is from human origin. Very resistant to gastric acidity (100% after 30 min at pH 4, 50% after 30 min at pH 3), Rosell-175 is not killed by bile salts even if its growth is inhibited(23). Moreover, as Rosell-175 is anaerobic, it will not be able to colonize the upper part of the intestine where the concentration of oxygen and bile is too high.

It will, however, colonize very well in the colon. In in vitro models, Rosell-175 adheres, only moderately, to human intestinal cells(24). However, it seems to be a good modulator of the immune system, efficiently helping the body fight against infectious agents(25). In the literature, B. longum has been reported to stimulate IL-1(26), decrease the number of Clostridia(27), Bacteroides and coliforms(28), and decrease some enzymatic activity in faeces, suspected to be involved in carcinogenesis(27, 29).

Bifidobacterium breve Rosell-70Rosell-70 is anaerobic. Consequently, it cannot colonize the upper part of the intestine where the concentration of oxygen is high. However, it grows very well in the colon. Rosell-70 is one the most adherent species of Bifidobacteria. It readily adheres to human intestinal cells and


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blocks the adherence of pathogenic bacteria such as E. coli(20). The full extent to which B. breve can modulate the immune system has not yet been tested; however, it has been reported to stimulate the secretion of IgA(21).

Each probiotic bacteria has individual characteristics: behaviour in the presence of oxygen, ability to ferment carbohydrates, resistance to acidity and bile, adhesion capacity… they will all have a specific site of action in the intestine.

Moreover, all probiotic bacteria don’t have the same health benefits. They differ in terms of which intestinal pathogens they can inhibit, their ability to modulate different components of the immune system… Thus, the 10 strains comprising ProBio SAP-90 will act synergistically to provide to the host better intestinal hygiene and an optimisation of probiotic health effect.

References1. Tournier-Château et al, Les probiotiques en alimentation animale et humaine. Lavoisier Tec&Doc, Paris, 1994.2. Hagiage M. La flore intestinale de l’équilibre au déséquilibre, Vigot, 1994.3. MizutaniT (1992) : The relationship betxeen microorganisms and the physiology of ageing. In functions of fermented milk, eds Y Nakazawa,

A Hosono pp. 305-324. London : Elsevier Applied Science.4. K.Johnson-Henry, P. Sherman, Research Institute, The Hospital for sick children, University of Toronto.Canada. internal results5. MC. Moreau, Probiotics and immunity. Probotics and Health: Summary and Perspective. Journée Institut Rosell. Proceedings of the Paris

Symposium, 2000.6. Easo JG, Measham JD, Munroe J and Green-Johnson JM (2002) Immunostimulatory Actions of Lactobacilli: Mitogenic induction of antibody

production and spleen cell proliferation by Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophilus. Food and Agricultural Immunology 14: 73-83.

7. Conway, P et al, 1987: Survival of lactic acid bacteria in the human stomach and adhesion to intestinla cells. J. Dairy. Sci. 70: 1-128. Barefoot, et al, 1983. Detection and activity of lactacin B, a bacteriocin produced by Lactobacillus acidophilus. Appl.Env. Microbiol: 45: 1808-

18159. Montes et al (1995): Effects of milk innoculated with Lactobacillus acidophilus or a yoghurt starter culturein lactos- maldigestion children.

J.DAIRY Sci. 78: 1657-1664.10. Gilliland et al (1990): Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a

hypocholesterolemic effect in humans. J.Dairy.Sci. 73: 905-911.11. Donnet-Hugues et al, Modulation of non specific mechanims of defenses by lactic acid bacteria : effective dose, J.Dairy., 1999, 8.2, 5, 863-869.12. Kocian J (1994), Furher possibilities in the treatment of lactose intolerance: Lactobacilli. Prakticky Lekar, 74: 212-21413. Tlaskal et al (1995); Lactobacillus acidophilus in the treatment of children with gastrointestinal tract illness. Ceslko-Slovenska Pedoiatrice, 51:

615-619, 1995.14. Wojoik et al (1996), Clinical trial of L.acidophilus. Department of gastroenterological surgery, Medical Academy, Warsaw Poland (internal

results).15. Danaone World Newsletter: L.casei16. Heinig MJ & Dewey KG (1996): Health advantages of breast feeding for infants: a critical review. Nutr. Res. Rev. 9 , 89-110.17. Tanaka R, & Shimosaka K (1982): Investigation of the stool frequency in elderly who are bedridden and its improvement by ingesting of

bifidus yogurt. Jpn. Geriatr. 19, 577-582.18. Grimaud JC, Bouvier M, Bertolino JG, Salducci J, Chiarelli P, & Bouley C (1992): Effects of milk fermented by Bifidobacterium on colonic transit

time. Hellenic J. Gastroenterol. 5, 104.19. Rasic JLJ (1993) : The role of dairy foods containing bifido-and acidophilus bacteria in nutrition and health. N. Eur. Dairy J. 48, 80-8820. Dr Kostrynska, Agriculture Canada (internal results)21. Yasui H, Nagaoka AA, Mike K, Hayakawa K, & Owaki M (1992): Detection of Bifidobacterium strains that induce large quantities of IgA.

Microbial Ecology in Health and Desease 5, 155-162.22. Danone World Newsletter : Kefir23. Institut Rosell research & development internal results24. Dr Kostrynska, Agriculture Canada (internal results)25. J.M. Green-Johnson, Dept of biology, Acadia University, Wolfville. Canada (unpublished results)26. Danone World Newsletter : Kefir27. Yasui H, Nagaoka AA, Mike K, Hayakawa K, & Owaki M (1992): Detection of Bifidobacterium strains that induce large quantities of IgA.

Microbial Ecology in Health and Desease 5, 155-162.28. Benno Y, & Mitsuoka T (1992): Impact of Bifidobacterium longum on human fecal microflora. Microbiol. Immunol. 36, 683-694.29. Ballongue J, Grill JP, & Baratte-Euloge P (1993): Action sur la flore intestinale de laits fermentés au Bifidobacterium. Lait 73, 249-256.30. Bouhnik Y (1993): Survie et effets chez l’homme des bactéries ingérées dans les laits fermentés. Lait 73, 241-247.

probio sap-90 - nfh property of institut rosell/lallemand for professional use only • not intended...

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