FAQ

Probiotics

1. What are probiotic micro-organisms?
   A committee of experts convened by the FAO (Food and Agricultural Organisation) and WHO (World Health Organisation) have defined probiotics as "live microorganisms which, when ingested in adequate amounts, confer a health benefit on the host". This definition, adopted by other bodies such as the International Life Science Institutes (ILSI), has been extended to probiotic food: “a food containing live micro-organisms in a sufficient quantity, throughout the shelf life of the product, that have beneficial effects on the health of the host”. Live micro-organisms can be yeast or bacteria, where each is defined by a specific strain name and registered in an international culture collection.
2. When were probiotics discovered? What is known about them?
   The concept that consuming live lactic bacteria could have a beneficial effect was first mentioned in the work of Teissier and Metchnikoff at the beginning of the 20^th century. As early as 1907, these biologists suggested that the lactic bacteria present in yogurt could be responsible for the longevity of Bulgarians, major yogurt consumers. Metchnikoff published the first results demonstrating a correlation between life expectancy and yogurt consumption. At the same time, yogurt was shown to have a beneficial effect when given to animals with diarrhea. In 1919, industrial development of yogurt and marketing in pharmacies began, with yogurt indicated for intestinal disorders. Later, foods and pharmaceutical products containing probiotics were marketed (e.g. yogurt, Ultralevure yeast).
   
   Studies currently being conducted in various countries are showing that probiotics can be considered increasingly promising for health.
3. What are the most common probiotics used in yogurt?
   The probiotics used in yogurt are micro-organisms that produce lactic acid, such as Lactobacilli, some Streptococci and Bifidobacteria.
   Lactobacillus L. casei
   L. rhamnosus
   L. acidophilus
   L. plantarum
   Bifidobacterium B. longum
   B. breve
   B. bifidum
   Some yeasts have also been shown to have beneficial effects on health. The most well-known are Saccharomyces S. cerevisiae boulardii.
4. What characteristics must a probiotic food-grade product have?
   Bacteria contained in a probiotic food-grade product must be:

   • present as live cells and preferably in sufficient quantity,
   • stable and viable during the entire shelf life of the product,
   • capable of conferring health benefits on the host.

   The question of survival in the host's gastrointestinal tract is not currently part of the definition, but it is considered an important criterion in determining whether a given probiotic is in fact able to confer its effects.
5. Are probiotics safe?
   In humans, lactic acid bacteria are natural commensal micro-organisms that are present in all the non-sterile parts of the body. In particular, lactic acid bacteria colonise the oral cavity, digestive tract and vaginal region.
   
   Historically, Lactobacilli and Bifidobacteria associated with foods have been considered safe.
   
   Moreover, lactic acid bacteria are considered saprophytes* devoid of pathogenicity on the basis of their widespread use throughout history in fermented foods such as yogurt, cheese, and other deli meats.
   
   * Saprophytes: micro-organisms that live in or on the body, but are not pathogenic, i.e. they are harmless for the body.
6. What are the clinical effects of probiotics?
   The claimed health effects vary according to genus, species and strain. The clinical effects of probiotics have been – and still are – studied in many trials.

   • Prevention and treatment of diarrhea: Several strains have been shown to be effective in the prevention or treatment of diarrhea, especially when caused by rotaviruses in children.
   • Gastrointestinal disorders and symptoms: In lactose intolerance, controlled trials with yogurts have been shown to benefit subjects with primary lactase deficiency, or malabsorption disorders following intestinal surgery.
   • Inflammatory diseases of the gastrointestinal tract: Several trials have demonstrated the benefits of probiotics in various inflammatory disorders of the digestive tract, such as chronic pouchitis, ulcerative colitis and disorders following antibiotic treatments.
   • Non-intestinal infections: Several strains of Lactobacilli have proven beneficial when used in prevention and/or treatment of various infections, such as respiratory diseases, vaginal infections or infection with Helicobacter pylori.
   • Allergies: Lactic bacteria have shown promising results in the prevention and treatment of atopic diseases.

   The clinical effects of probiotics are directly derived from their interaction with the intestinal mucosa.

Probiotics and the intestine

7. What is the intestinal barrier?
   The intestine may be described as a complex ecosystem comprising three entities in continuous contact and interaction: the host cells, the components of the ingested food bolus and the intestinal microflora.
   
   The intestine is responsible not only for food digestion, but also for an entire range of other hormonal, motor, nervous and immune functions, several of which are responsible for establishing an effective line of defence against external aggression. This important defensive function of the intestine is based on three key components:

   • The microbiota includes a considerable number of bacteria, approximately 100 trillion, comprised of over 400 different species. The bacterial flora has a beneficial effect on the body's defence system by fighting potentially pathogenic bacteria with various mechanisms.
   • The intestinal mucosa represents a considerable surface area (about 200 square metres) due to its characteristic microvillus. This exchange surface facilitates nutrient absorption and helps to protect the body. As a physical barrier, the intestinal epithelium is a site of numerous interactions between the external and internal media. Integrity and trophicity are therefore vital to ensure good functioning.
   • The intestinal immune system. About 70% of the human immune system is located in the intestine, where specialised cells play an important role as the first line of defence against several bacterial and environmental assaults. The gut-associated lymphoid tissue (GALT), is the major gateway for stimulating immune response, local at first, and later throughout the immune system. For instance, the Peyer’s patches are lymphoid tissues for GALT, which are the entry points where immunity is challenged.

   All three components comprise what is often referred to as the “intestinal barrier”. The intestine, the most important lymphoid organ, is a complex organ that plays a major role in the defence of the body. Impairment of one or more of the three components can cause disease.
8. How does the intestine contribute to building immunity?
   From a sterile intestine at the time of birth, introduction of various food antigens stimulates acquired immunity to build an efficient intestinal line of defence. Diet diversification is critical, as it represents a range of potentially harmful organisms. Building balanced intestinal microbiota is essential. Therefore, enhancing colonisation by beneficial bacteria prevents the growth of harmful strains. The oral route is preferred for children, since the intestine is the main lymphoid organ in the body, and the number of Peyer’s patches rapidly increases in the early years of life.
9. How do probiotic bacteria interact with the three intestinal lines of defence?
   Probiotics have several effects:

   • On the intestinal microflora, by inhibiting colonisation and growth of harmful bacteria
   • On the intestinal mucosa, by enhancing resistance to infection
   • On the local immune system (GALT), by modulating immune parameters and mucosal inflammation.

DanActive^TM, a probiotic food

10. What is the difference between DanActive^TM and standard yogurt?

    DanActiveTM contains L. casei DefensisTM,
    Yogurt Lactobacillus bulgaricus Streptococcus thermophilus	DanActiveTM Lactobacillus bulgaricus Streptococcus thermophilus + Lactobacillus casei DEFENSIS (108 cfu/g)

11. Is DanActive^TM a probiotic food?
    According to the ILSI (International Life Sciences Institute) definition, DanActive^TM is a probiotic drink, which contains two commonly-used yogurt strains whose effects have been known for more than 80 years (Danone yogurts were sold by pharmacists for children suffering from chronic diarrhea) and a specific strain known as Lactobacillus casei DN 114-001, its scientific name, or Lactobacillus casei DEFENSIS, its brand name.
    
    Probiotic foods contain bacteria that must be:

    • present as live cells and preferably in high quantities,
    • stable and viable during the entire shelf life of the product,
    • capable of conferring health benefits on the host.

    DanActive^TM contains the two standard yogurt strains. Lactobacillus bulgaricus and Streptococcus thermophilus are found in the finished product at concentrations of 10⁷ and 10⁸ cfu/g, respectively, and a specific strain from Danone Research Lactobacillus casei DN 114-001 is found at a concentration of 10⁸ cfu/g, representing 10 billion cfu per bottle. These concentrations are guaranteed for the entire shelf life of the product.
    
    In recent years, Groupe Danone has developed a unified scientific approach and has shown that DanActive^TM and/or Lactobacillus casei DN 114-001 confer biological, physiological or clinical effects in different types of models, and that these effects are associated with the optimisation of certain bodily functions, resulting in improved defence against external aggressions and against infections in particular.
12. Is DanActive^TM a medicinal drug?
    No. DanActive^TM is a food-grade product with a preventive effect: it helps strengthen the body’s natural defences.
13. What is the nutritional composition of DanActive^TM?

    	Strawberry		Vanilla		Blueberry		Cranberry- Raspberry
    	Per 100 ml	% RDI	Per 100 ml	% RDI	Per 100 ml	% RDI	Per 100 ml	% RDI
    Calories/calories	90		90		90		90
    Fat/lipides (g)	1,5	2 %	1,5	2 %	1,5	2 %	1,5	2 %
    Saturated fat/saturés	1		1		1		1
    + Trans fat/trans	0		0		0		0
    Total		5 %		5 %		5 %		5 %
    Cholesterol/cholestérol (mg)	5	2 %	5	2 %	5	2 %	5	2 %
    Sodium/sodium (mg)	45	2 %	40	2 %	40	2 %	45	2 %
    Potassium/potassium (mg)	135	4 %	130	4 %	130	4 %	135	4 %
    Carbohydrates/glucides (g)	17	6 %	17	6 %	17	6 %	17	6 %
    Fibre/fibres (g)	0	0 %	0	0 %	0	0 %	0	0 %
    Sugars/sucres (g)	17		17		17		17
    Protein/protéines (g)	3		3		3		3
    Vitamin/vitamine A		0 %		0 %		0 %		0 %
    Vitamin/vitamine C		0 %		0 %		0 %		0 %
    Calcium/calcium		10 %		10 %		10 %		10 %
    Iron/fer		0 %		0 %		0 %		0 %

14. Does DanActive^TM contain genetically modified organisms (GMOs)?
    No. Danone is committed not to include GMOs in the products it manufactures.
15. Does DanActive^TM contain cholesterol?
    Like all dairy products, DanActive^TM contains cholesterol, but in microscopic quantities. More importantly, DanActive^TM is low in saturated fats, the main dietary constituent affecting blood cholesterol.
16. Is DanActive^TM suitable for children?
    As a fermented dairy product, there are no contraindications to consumption of DanActive^TM for people of all ages.
    
    Moreover, Lactobacilli has never been associated with an allergic reaction, nor have any cases been reported of allergic reactions to lactic acid bacteria in general, including clinical studies involving high-risk allergic individuals.
    
    The presence of the probiotic strain L. casei DEFENSIS in DanActive^TM is therefore not considered to cause additional allergenic risk.
17. Is DanActive^TM suitable for diabetics?
    A 100 ml serving of DanActive^TM contains 17.0 g of carbohydrates. This is always clearly indicated on the packaging. Diabetics are advised to limit their sugar intake. They can therefore safely consume DanActive^TM, provided they include the carbohydrate content in their daily carbohydrate allowance.
18. Is DanActive^TM suitable for pregnant women?
    There is no specific contraindication regarding consumption of DanActive^TM by pregnant women.
19. Can DanActive^TM cause allergic reactions?
    There are no reported cases of DanActive^TM causing an allergic reaction. Several probiotic strains have shown beneficial effects in preventing or reducing allergic symptoms, but to this day no studies in this field have been done with DanActive^TM. As a dairy product, DanActive^TM is contraindicated for people allergic to cow’s milk proteins.
20. What is the recommended daily intake of DanActive^TM?
    Sufficient consumption can be achieved by drinking one bottle per day, with breakfast or at any time of day.
21. Can DanActive^TM be heated?
    No. To avoid killing live cultures, DanActive^TM should not be heated.
22. Does DanActive^TM survive in the digestive tract?
    During gastrointestinal transit, bacterial strains undergo drastic physiological stress (e.g. acidity, digestive enzymes and bile salts), affecting their survival and thus their health benefits.
    
    Animal studies have demonstrated the ability of DanActive^TM to survive in the gastrointestinal tract. Studies with humans have confirmed the data obtained with animals showing that Lactobacillus casei DN 114-001 survives transit through the gastrointestinal tract, and that the probiotic can be isolated from stools at levels close to 10⁶ to 10⁸ cfu per gram. Moreover, it is a transient bacteria and does not colonise the intestinal tract. Therefore, DanActive^TM can confer its benefits only when it is consumed regularly.
23. Does DanActive^TM have an effect on the intestinal microbiota?
    In cases or models in which the flora does not appear correctly stabilised, DanActive^TM favourably modulates the flora and restores equilibrium.
24. Does DanActive^TM affect the intestinal mucosa?
    The intestinal mucosa is a site of numerous interactions between the external and internal environments. Integrity and trophicity are therefore vital to ensure good functioning. Studies in vitro and ex vivo have demonstrated that DanActive^TM improves the trophicity and functioning of the intestinal epithelium.
25. Does DanActive^TM interact with the immune system?
    DanActive^TM helps strengthen the body’s natural defences, acting on the gut-associated lymphoid tissue (GALT) which is the major gate for stimulating an immune response, local at first, and later systemic.
    
    GALT: Ex vivo studies have demonstrated the ability of DanActive^TM to interact with immunocompetent cells of the intestinal mucosa, thus affecting the mucosa’s defence mechanisms.
    
    Systemic immunity: DanActive^TM has shown to have an effect on the immune cells of subjects experiencing situations that can weaken natural defences, i.e. age, stress and lack of exercise.
26. What are the health benefits of DanActive^TM?
    As well as having overall health benefits, DanActive^TM has proven beneficial effects on the body’s natural defences by acting on the three intestinal lines of defence.
    
    Effects on the three lines of defence:

    • Effects on the microbiota: Consumption of L. casei DN 114-001 modified the composition and metabolism of rodents carrying human flora. In children, supplementation with DanActive^TM resulted in a higher percentage of children with a fecal population of Lactobacilli. To sum up, in cases or models in which the flora does not appear correctly stabilised, DanActive^TM favourably modulates the flora and restores balance. Regular consumption of DanActive^TM increases the number of probiotic bacteria in the intestinal flora. This is known to reduce the development of a broad range of enteric pathogens.
    • Effects on the intestinal mucosa: By acting on the intestinal epithelium at different levels, DanActive^TM enhances the quality of the intestinal epithelium and mucus. Studies on animal models have shown its ability to enhance growth and differentiation of rodent epithelial cells, thus providing better protection against harmful bacteria. Studies in vitro with human cells confirmed a beneficial effect on permeability and inhibition of microbial adherence.
    • Effects on the intestinal immune system (GALT*): In animal models, mucosal colonisation with L. casei DN 114-001 modulated the inflammatory response in rats, and food supplementation with DanActive^TM resulted in an improvement of the local immune response, preventing E. coli infection in mice. Studies ex vivo with DanActive^TM demonstrated its ability to interact with immunocompetent cells of the intestinal mucosa, thus modulating the local immune response, including the response against pathogenic bacteria such as Shigella.

    Effects on the gastrointestinal tract:

    • In children, DanActive^TM has been shown to reduce the incidence and severity of diarrhea.
    • Supplementation with DanActive^TM confers an enhanced therapeutic benefit on H. pylori eradication in children with gastritis on triple antibiotic therapy.

    Effects on the immune system:

    • Supplementation with DanActive^TM has been shown to reduce the duration of winter infections (intestinal and respiratory) in free-living elderly subjects.
27. Is it possible to consume DanActive^TM during an episode of diarrhea?
    Studies performed in children have shown that DanActive^TM reduces the incidence and/or severity of diarrhea. It may therefore be wise to consume DanActive^TM during episodes of diarrhea. Diarrhea involves an impairment of intestinal function and is frequently associated with lactase deficiency or non-functioning.
    
    Consuming probiotic yogurt such as DanActive^TM thus provides two benefits:

    • Enhanced digestibility, since part of the lactose has already been predigested
    • Restored equilibrium of the diarrhea-impaired intestinal flora.
28. Is it possible to consume DanActive^TM while taking antibiotics?
    Antibiotic treatment destabilizes the intestinal flora; this situation is therefore one of the first indications for probiotics. Supplementation with DanActive^TM was shown to confer an enhanced therapeutic benefit on H. pylori eradication in children with gastritis treated by triple antibiotic therapy. Consuming DanActive^TM for the duration of antibiotic treatment can prove a good way of protecting the intestinal ecosystem from the adverse effect of the antibiotic on endogenous intestinal flora, thus enhancing systemic tolerability.
29. Does DanActive^TM have health benefits apart from digestive tract benefits?
    One study so far has demonstrated that supplementation with DanActive^TM reduces the duration of winter infections (intestinal and respiratory) in free-living elderly subjects.
30. What are the safety data for DanActive^TM?
    Many species of Lactobacilli are used in the fermentation of foodstuffs without risk to consumers. The species L. casei has been used in probiotic products for many years, with no reports of any health problems or risk of infection.

    • In 12 published clinical studies where 766 subjects ingested DanActive^TM, no adverse events were reported due to the product.
    • Toxicological studies have been performed on mice. No toxic effects were shown, even at high doses, the equivalent of which would be 1.75 litres/day for a 70 kg man.