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Probiotics.farhat
- 1. Demystifying Probiotics: Role in Health and Disease Michel Farhat, PhD Manager, Professional & Technical Affairs Procter and Gamble Personal Healthcare
- 2. Probiotics in the Current Marketplace • Growing public and scientific interest in probiotics • Global probiotic market estimated at billions of dollars per year • Hundreds of probiotics available as food, dietary supplements, skin and pet products
- 3. Awareness of Probiotics in the Current Marketplace Natural Marketing Institute (NMI) 2009 Supplement/OTC/Rx Database™
- 4. Probiotics in the Current Marketplace Natural Marketing Institute (NMI) 2009 Supplement/OTC/Rx Database™
- 5. U.S. Specialty Supplement Sales by Product in 2009 Source: Nutrition Business Journal estimates (consumer sales) Based on NMI’s Health and Wellness Trends Database U.S. Health and Wellness Industry 2009 Sales = $112.3 Billion U.S. Health and Wellness Industry 2009 Sales = $112.3 Billion Functional and Fortified Foods and Beverages in 2009 = $40.5 Billion Functional and Fortified Foods and Beverages in 2009 = $40.5 Billion Vitamins, Minerals, Herbals and supplements in 2009 = $23.3 Billion Vitamins, Minerals, Herbals and supplements in 2009 = $23.3 Billion Probiotic supplements in 2009 estimated at $405 million Probiotic supplements in 2009 estimated at $405 million
- 6. Human Microbiome Project • The Human Microbiome Project (HMP) aims to characterize the microbial communities found at several different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and to analyze the role of these microbes in human health and disease. http://commonfund.nih.gov/hmp/
- 7. 7 17 61 91 191 453 432 564 307 271 127 421 294 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 (Number of published clinical studies on probiotics) Polynomial trend line shows uniform, consistent growth Clinical Research Activities Trended Source: www.ncbi.nlm.nih.gov/pubmed
- 8. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 9. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 10. Human bodies are highly colonized 100 trillion microbial cells on/in human body: mouth, intestine, vagina, skin 10x the number of human cells in our bodies >500 different bacterial species in intestine
- 11. Gut Colonization • Colonization of the gastrointestinal tract begins immediately after birth • Colonization pattern is affected by: – mode and type of birth delivery, – initial diet – geographical location • Initial bacterial colonization (normal) starts from a “Germ free” intrauterine environment and is populated through maternal vaginal/fecal flora and oral feeding (breast milk vs formula) • Complete adult colonization : 18 – 24 months
- 12. Taxonomic distribution of microorganisms in mother and baby. Reid et al, Nature Reviews Microbiology 2010
- 13. Functions of the Intestinal Flora
- 14. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 15. Probiotics • First described by Metchnikoff in 1908 • “Live microbial food ingredients that alter the microflora and confer health benefit”
- 16. What are Probiotics? FAO/WHO Definition • “Live microorganisms which when administered in adequate amounts confer a health benefit on the host” • Probiotic microorganisms can be found in both supplement form and as components of foods and beverages. The Joint Food and Agriculture Organization/World Health Organization Working Group
- 17. Different types of microbes used as probiotics • Lactobacillus • Bifidobacterium • S. thermophilus • Saccharomyces • Propionibacterium • Bacillus • Enterococcus • E. coli Images courtesy of Prof. Lorenzo Morelli
- 18. Prebiotics • “Non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and activity of one species or a limited number of species of bacteria in the colon” Duggan et al, 2002. – Oligosaccherides – Inulin – Fructose oligosaccherides – Fiber – Fiber supplements
- 19. Prebiotic vs Probiotic Prebiotic • Usually carbohydrate • Not alive • Beneficial health effect • Food ingredient • Act on microbiota • Focus is colon, but broader effects also seen Probiotic • Microorganism • Alive • Beneficial health effect • Food, dietary supplement, drugs • May act on microbiota, but other mechanisms • Can act on numerous sites around the body
- 20. Synbiotic = Probiotic + Prebiotic
- 21. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 22. Sherman et al. Nutr Clin Pract, 2009; 24(1):10-14 Potential Mechanisms of Action of Probiotics
- 23. IFNγ IL10 (Bif) IL10/IL12 (LPS) IL10/IL12 (Bif) (LPS) IL10/IFNγ (Bif) (LPS) IL10/IFNγ (Bif) (LPS) healthy subject TNFα (LPS) TNFα (Bif) (LPS) IL12 (LPS) IL12 (Bif) (LPS) IFNγ (LPS) IFNγ (Bif) (LPS) Pro-inflammatory cytokines Pro-inflammatory cytokines Anti-inflammatory cytokines Anti-inflammatory cytokines IBS at pre-feeding stage IBS at wk-3 feeding stage B. infantis 35624 modulates systemic immune state of IBS toward healthy subject Higher Level than healthy Lower Level than healthy TNFα IL12 IL10 (LPS) IL10 (LPS) TGFβ/IL12 (LPS) TGFβ/IL12 (LPS) Chen et al, Gastroenterology 2005; 128 (4 suppl 2): A661Gastroenterology 2005; 128 (4 suppl 2): A661
- 24. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 25. Gut function Acute diarrhea AAD, travelers diarrhea C. difficile Lactose digestion IBS symptoms Colic Inflammatory bowel conditions Gut pain sensation Allergy Atopic dermatitis Asthma Oral microbiology Dental caries Colds, respiratory infections Skin microbiology, inflammation Vaginal infections Metabolic syndrome Obesity, Diabetes Encompassing effects •Growth parameters of undernourished children •Reduced absences from work, daycare •QOL Diverse Targets for Probiotics
- 26. Probiotics in the Treatment of Gastrointestinal Disorders IBD Ulcerative colitis Crohn’s disease Pouchitis Constipation Lactose Intolerance H. pylori Eradication Diarrhea Acute infectious Antibiotic-associated C. difficile
- 27. Levels of Probiotic Activity Adapted from Rijkers GT, et al. J Nutr. 2010;140:671S-676S. Interfere with growth or survival of bacteria in gut lumen Improve mucosal barrier function and mucosal immune system Affect systemic immune system
- 28. Summary of Key Randomized Controlled Trials of Probiotics in IBS William D Chey, Reviews in Gastroenterol 2010
- 29. Probiotics in C. Difficile-Associated Disease BB=Bifidobacterium bifidum; LA=Lactobacillus acidophilus; LGG=Lactobacillus rhamnosus GG; LP=Lactobacillus plantarum 299v; SB=Saccharomyces boulardii MacFarland LV. Am J Gastroenterol. 2006;101:812-822. RCTs of Probiotics for Treatment of C. difficile Disease
- 30. S. boulardii Is Effective in Patients with Recurrent C. difficile Disease CDD=Clostridium difficile-associated disease McFarland L, et al. JAMA. 1994;271:1913-1918. Initial CDD CDDrecurrence,% S. boulardii (n=31) Placebo (n=33) P=NS Recurrent CDD Control (n=34) P=0.04 Patients received standard antibiotics (vancomycin or metronidazole) and S. boulardii 1 g/day or placebo for 4 weeks. CDDrecurrence,% S. boulardii (n=26)
- 31. Probiotics for the Prevention of Antibiotic Associated Diarrhea Mixtures included: Lactinex = L. acidophilus and L. bulgaricus; Lactobacillus acidophilus and Bifidobacterium lactis; Lactobacillus acidophilus and Bifidobacterium infantis. McFarland, Am J Gastroenterol 2006; 101(4): 812-822.
- 32. L. acidophilus NCFM and/or B. animalis Bi-07 reduces symptoms of colds/flu in Chinese children . • DBPC study • N=326 children (3–5 years of age) • Probiotic: NCFM or NCFM+Bi-07, dried powder mixed in milk • Daily dose 1010 cfu/d • 6 months administration Leyer et al. 2009. Pediatrics;124(2):e172-9
- 33. Parameter Controls BB-12 L reuteri P Value n 60 73 68 Days with fever 0.83 (0.50–1.16) 0.86 (0.33–1.39) 0.17 (0.04–0.30) <.001* Episodes of fever 0.41 (0.28–0.54) 0.27 (0.17–0.37) 0.11 (0.04–0.18) <.001 Days with diarrhea 0.59 (0.34–0.84) 0.37 (0.08–0.66) 0.15 (0.12–0.18) <.001 Episodes of diarrhea 0.31 (0.22–0.40) 0.13 (0.05–0.21) 0.02 (0.01–0.05) <.001 Days with respiratory illness 0.60 (0.31–0.89) 0.68 (0.17–1.19) 0.38 (0.10–0.66) .169 Respiratory illness episodes 0.24 (0.13–0.35) 0.25 (0.15–0.35) 0.17 (0.08–0.26) .457 Clinic visits 0.55 (0.42–0.68) 0.51 (0.34–0.68) 0.23 (0.12–0.34) .002* Absences from child care 0.43 (0.22–0.64) 0.41 (0.19–0.63) 0.14 (0.07–0.35) .015* Prescriptions of antibiotics 0.19 (0.09–0.29) 0.21 (0.12–0.30) 0.06 (0.01–0.12) .037 L reuteri versus BB-12 supplemented Infant Formula and Infections in Child Care Centers Weizman et al, Pediatrics, Jan 2005; 115: 5 - 9
- 34. Impact of Probiotics on prevention of eczema Wickenset et al. 2008. J Allergy Clin Immunol. 6 mo treatment of mother from 35 wks gestation to 6 months of age; infants through 2 years of age
- 35. “Human gut microbes associated with obesity” Ley, et al. NATURE 2006
- 36. Resistance to diet-induced obesity in germ-free mice Backhed et al., PNAS 2007 , 104 (3): 979–984
- 37. Misconceptions about Probiotics • Probiotics are live active cultures • Probiotics are synonymous with native commensal bacteria • More is not better – Dose (1 billion vs 10 billion vs 450 billion) – Number of strains • The effect of probiotics is genus specific
- 38. Dosage of Probiotics • The dose of probiotics is usually expressed as the number of colony forming units (CFUs) • The required dose of probiotics may vary greatly for different strains and the specific health effect under investigation • Probiotic effects should be considered dose-specific • Dose listed on the label must be based on studies that show a health effect in humans.
- 39. Effects are considered strain-specific for most probiotic attributes •Different strains of the same species can be different •Clinical support to substantiate claims must be for each probiotic strain
- 40. Maintaining remission of ulcerative colitis with Escherichia coli Nissle 1917 Kruis et al., Gut. 2004 Nov;53(11):1617-23
- 41. Effect of Different Probiotic Strains on Cytokine Production
- 42. Comparative Claims Comparative claims among products cannot be made unless a product contains: -Same probiotic strain -Same dose -Same formulation
- 43. Probiotics: Quality Control • Source (animal vs human; normal vs diseased) • Formulation (vehicle) • Safety (in at risk populations) • Characterization (strain purity) • Viability (Cfu delivered) • Dose (Dose-response studies) • Combinations/cocktails (Different effects of different bacterial strains)
- 44. Dose listed on label should accurately reflect dose in product at the end of shelf life
- 45. Safety of Probiotics • The safety of probiotics is strain-specific. • The genus and species of the microbe being used should be assessed with respect to: – Genetic stability, – Metabolic activities, – Potential for pathogenicity or toxicogenicity – Method of administration – Level of exposure, – Health status of the users – Physiologic functions • Few correlations between probiotic use and adverse events have been demonstrated • Although probiotics marketed as foods and dietary supplements should be safe for the generally healthy population, their safety has not been asserted on individuals with underlying health conditions.
- 46. Probiotics in Health and Disease • Gut Microbiota • What are Probiotics? • Potential Mechanisms of Action • Therapeutic Targets of Probiotics • Strain Specificity • Quality Control • Regulatory Guidelines
- 47. Regulatory Environment • Probiotics in the US are food or dietary supplements and therefore regulated by the Dietary Supplements Health and Education Act (DSHEA) • Structure/Function Claims for impact on the structure/ functioning of the normal human body • This food can support a healthy immune system • This supplement can help maintain a healthy digestive tract • Claims are required by FDA to be “truthful and not misleading” and supported by “competent and reliable scientific evidence”
- 48. Not Allowable Claims The FDA does not allow any statements on a food or supplement that would communicate benefits on: Reducing the risk of acute diseases (colds, flu, GI infections) Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS) Improving therapeutic efficacy of a drug Managing side effects of a drug (e.g., antibiotics) (Even if such use is recognized as safe in the target populations)
- 49. DSHEA: Probiotic Claims Supports a healthy immune system* Helps keep your microflora in balance* Helps build and maintain a healthy digestive system* Disclaimer: *This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
- 50. Regardless of the claim, it must be substantiated There are no generic probiotic claims Claim substantiation must be based on a specific strain Probiotic claims
- 51. Challenges for consumers • Lots of misinformation • Consumers don’t know what products are good ones • Limited third party assessment of health benefit claims • Disconnect between scientific evidence available on probiotics and what regulatory authorities will allow to be communicated • All products in USA are foods or supplements not intended for use in non-healthy populations
- 52. How to choose a probiotic? • Strain: Different strains of even the same species can be different • Clinically proven: Probiotics must be tested in humans and shown to have health benefits – Product web sites should cite efficacy studies • Truthful claims: Any claim made on a product, no matter how general, is supposed to be truthful and not misleading – Not all manufacturers have efficacy substantiation ISAPP guidelines at www.isapp.net
- 53. How to choose a probiotic? • Safety: Patients should consult their doctor’ if they have health concerns • Dose: Product should match levels used in human studies showing benefits – Different probiotics have been shown to be effective at different levels – It is not possible to provide one count for all “probiotics” • Food or supplements? Probiotic content is generally more important than the way they are consumed. ISAPP guidelines at www.isapp.net
- 54. Conclusions • Probiotic bacteria confer health benefits by bolstering protective, structural and metabolic functions in the human body. • Not all probiotics are equal. • Disconnect between scientific evidence and allowable claims. • Claims should be substantiated with well-controlled clinical studies. • Products should be characterized for content and stability.
Notes de l'éditeur
- Human bodies are highly colonized, with the number of microbial cells outnumbering human cells by a factor of 10 to 1. Recognizing the profound impact of microbes to human health, global initiatives are currently underway to study native microbial communities and how they correlate with human health and disease. Although a common perception is that microbes are bad—an idea fueled by an abundance of information about pathogenic bacteria, yeast, and viruses and their associated morbidity and mortality, a growing body of research is documenting the diverse ways that certain other microbes, called probiotics, can contribute to human health.
- Probiotics are not only making an impact in research, but they are also becoming a growing trend in the global marketplace. The global market for commercial probiotic products is now estimated at billions of dollars per year (Stanton, et al., 2001). Hundreds of probiotic foods and dietary supplements are available and claim to offer a variety of health benefits in different parts of the body including the gastrointestinal system. Probiotics have also been included in skin care products and pet food.
- In the VMS category in 2008, probiotics constituted about 9% of total sales accounting for over $400 million in revenue. But the category continues to grow
- Exposure to this microbiome appears to be critical for the development and maturation of a healthy immune system. Colonization of the gastrointestinal tract begins immediately after birth, and occurs within a few days. Mode of delivery (i.e. natural birth versus caesarean section), initial diet (i.e. breast versus formula feeding), geographical location (i.e. developed country vs developing country) and type of delivery (i.e. home birth versus hospitalized birth) all contribute to the colonization pattern. As we mature, the population of Bifidobacterium decreases to about 3–6% of the fecal flora, then declines even further with advanced age.
- Immediately after birth, humans become colonized by a range of microorganisms, particularly on the skin, oronasopharyngeal area, gastrointestinal tract and urogenital tract. The host and its microbiome have developed mechanisms to not only protect against infection, but also restore microbial homeostasis, even without pharmaceutical therapy. The genus-level distributions are shown for a sample of mothers and their babies, grouped according to the delivery method of the babies (vaginal or by Caesarian section (C-section)). The data shown are averaged for each group.
- The native colonizing bacteria perform various protective, structural, and metabolic functions on the intestinal mucosa, leading to the concept of the microbiota as a “virtual organ within an organ.” In fact, the microbiota have been called a “metabolic organ,” exquisitely tuned to our physiology that performs functions that we have not had to evolve on our own.” Although the myriad functions of the native microbes colonizing humans are just beginning to be understood, it is believed that certain other microbes that are consumed and added to our microbial mix—known as probiotic bacteria—may use these same mechanisms to enhance or stabilize normal colonizing microbes
- The concept of healthy bacteria has been documented as far back as Early Roman History (Plinio, 76AD) and was advocated by the nobel prize winner Eli Metchnikoff in 1907
- The joint committee of FAO and WHO have provided a definition of probiotics which is now widely accepted. They define probiotics as live microorganisms ……..on the host” These Probiotics organisms could be found in foods and beverages or delivered through a supplement.
- This is a list of the different groups of microorganisms which have been identified as having probiotic properties. The most widely studied and commonly used probiotics are the Lactobacilli and Bifidobacteria. Lactobacillus: Gram positive facultative anaerobe. In humans they are present in the vagina and the gastrointestinal tract, where they are symbiotic Bifidobacteria are Gram-positive procaryotes that naturally inhabit the gastrointestinal tract of humans and other warm-blooded animals. In breast-fed newborn infants, bifidobacteria constitute 95% of total gut bacterial population. As we mature, the population of Bifidobacterium decreases to about 3-6% and declines further with advanced age
- Schematic depiction of potential mechanisms of action by which probiotics can promote GI health. Probiotics (PB) and surface-layer proteins (slp) competitively exclude microbial pathogens from mucosal surfaces. Tight junction proteins, such as zona occludins (ZO)-1 and claudin1, remain intact and thereby prevent both uptake of intact macromolecules and translocation of viable organisms to mesenteric lymph nodes. Probiotic strains possess the ability to modulate signal transduction pathways to block activation and translocation to the nucleus of the transcription factor, nuclear factor-kappa B (NF-κB), interferon-γ (IFNγ), and mitogen-activated protein kinases (MAPK). Through a cascade of signaling events, probiotics can enhance production and secretion of anti-inflammatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) by a subset of immune cells, referred to as T regulatory cells (Tregs). Humoral immune system responses to probiotics include enhanced production of immune globulins, including secretory immunoglobin A (sIgA). Innate immune responses to probiotics include increased mucin and trefoil factor production by goblet cells (G) and enhanced production of antibacterial defensins by Paneth cells (PC) and intestinal epithelia. DC, dendritic cell; P, pathogen; TC, T lymphocyte.
- Study subjects: 13 self-reported IBS and 10 healthy individuals. Treatment regimen: Subjects in both populations were fed daily with 4-ounce milk (containing 1010 cfu Bifidobacterium infantis 35624) for 3 weeks. Systemic cytokine profile: Before and after B. infantis 35624 feeding, one PBMC (peripheral blood mononuclear cell) from each individual was cultured in vitro with either vehicle or a stimulant (LPS, B. infantis 35624) for 3 days. Culture supernatants were collected for cytokine analyses by bead-based ELISA assay. Results: Baseline (Pre-feeding with Bifantis) Spontaneous (without stimulation) production: Cells isolated from IBS showed a similar cytokine level as those from the healthy individuals. With LPS stimulation: Cells isolated from IBS revealed an aberrant cytokine pattern of: Increased pro-inflammatory cytokines (IL12, TNFa, IFNg); Decreased ratio of anti-/pro-inflammatory cytokines (IL10/IFNg, TGFb/IL12). Post-feeding with Bifantis: Without stimulation: Cells isolated from IBS continued to show a similar cytokine level as the cells isolated from healthy individuals. With LPS or B. infantis 35624 stimulation: Cells isolated from IBS showed a more normal balance of cytokines: Decreased pro-inflammatory cytokines (IL12, TNFa, IFNg). Increased anti-inflammatory cytokine (IL10). Increased ratio of anti-/pro-inflammatory cytokines (IL10/IL12, IL10/IFNg, TGFb/IL12).
- Although information about the microbial composition of the intestinal ecosystem in health and disease remains incomplete, the intestine contains extensive microbiota—100,000 billion bacteria, located mainly in the colon and comprising hundreds of species of bacteria Probiotic research suggests a range of clinical applications for various probiotics in GI disorders Although the use of probiotics in diarrheal disease has been most extensively studied to date, a growing number of studies have explored the use of probiotics for use in IBD, with particularly promising data in pouchitis; constipation; lactose intolerance; and for use as adjuntive therapy in H. pylori eradication Reference: World Gastroenterology Organisation. Probiotics and prebiotics. May 2008.
- Although the mechanisms of action of probiotics are largely unknown at the molecular level, a probiotic can act: Within the gut lumen by direct interaction with the complex ecosystem of the gut microbiota; By interaction with the gut mucus and epithelium, including barrier effects, digestive processes, mucosal immune system, and enteric nervous system; and Through signaling to the host beyond the gut to the liver, systemic immune system, and other potential organs such as the brain Reference: Rijkers GT, Bengmark S, Enck P, et al. Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research. J Nutr. 2010;140:671S-676S.
- An increasing number of randomized controlled trials (RCTs) have evaluated the efficacy of probiotics in patients with IBS. Unfortunately,many of the available studies are encumbered by methodological limitations such as small sample sizes, lack of adequate blinding, short study duration, use of non-validated study endpoints, and failure to report an intention-to-treat analysis. Furthermore, results between studies are difficult to compare owing to variations in design, probiotic dose and strain and results from these trials should therefore be interpreted with some caution. Nevertheless, some positive results have been noted. Overall, studies have typically included strains of Lactobacillus species or Bifidobacterium species, along with different probiotic combinations such as VSL#3 and SCM-III
- Meta-analysis of 6 RCTs in adults with prior antibiotic exposure from 1977 to 2005 indicated that probiotics have a significant protective effect for C. difficile diarrhea (RR=0.59, 95% CI=0.41, 0.85)1 A funnel plot indicated the absence of publication bias 5 of 6 studies were treating patients with established C. difficile disease and the probiotic was combined with standard antibiotics The duration of probiotic treatment varied from 3-5 weeks Types of probiotics used included S boulardii, L. rhamnosus GG, L. plantarum 299v, and a mixture of L. acidophilus and B. bifidum Of the strains tested, only S. boulardii showed significant reductions in recurrences of C. difficile disease1 This analysis has been criticized for combining the results from 1 study of preventing C. difficile diarrhea with results from 5 treatment studies, and other methodologic flaws (eg, pooling data on different antibiotics, different conditiions)3 Despite these results, a recent Cochrane review of 4 RCTs of probiotics with conventional antibiotics (vancomycin or metronidazole) concluded that there is insufficient evidence to support the use of probiotics alone in the treatment of C. difficile colitis2 References: MacFarland LV. Meta-analysis of probiotics for the prevention of antibiotic-associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101:812-822. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev. 2008;23:CD004611. Wolvers D, Antoine JM, Myllyluoma E, et al. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of infections by probiotics. J Nutr. 2010;140:698S-712S.
- In the largest study to date, S. boulardii in combination with vancomycin or metronidazole was associated with a significant decrease in CDD recurrence in patients who had a history of at least 1 CDD episode. In this double-blind, randomized, placebo-controlled, parallel-group study, 64 patients with an initial episode of CDD and 60 with a history of at least 1 prior CDD episode received S. boulardii 1 g/day for 4 weeks or placebo in combination with either vancomycin or metronidazole. S. boulardii was effective in patients with recurrent CDD, but not in patients with initial CDD. Reference: McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994;271:1913-1918.
- Outside the gut, probiotics have been shown to protect and reduce flu symptoms. This is a study published last year looking at the effect of 2 bacterial strains on symptoms of cold and flu in chinese children, and you can see that there was a signidicant reduction in symptom duration, fever, cough, antibiotic use and absenteeism with probiotic administration. The combination of strains was more effective that the lactobacillus strain alone.
- Similarly another study also published in Pediatrics looked at the effect of feeding infants formula supplemented with the probiotic strain Lactobacillus reuteri, on the rate of infections in child care centers. They found that the duration of fever and diarrhea were significantly reduced with probiotic feeding vs placebo.
- The study shows that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss. The findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
- GF animals are protected from diet-induced obesity Adult male C57BL/6J mice were conventionalized 3 weeks before they were switched to a high-fat Western diet. Initial weight was recorded (25.50.4 and 26.60.7 g for GF and conventionalized mice, respectively). Weight gain was monitored weekly for 8 weeks and compared with GF mice (n5 per group). Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota.
- Despite the growing interest in probiotics, there are a number of common misconceptions about these products. Probiotics are not the same as live active cultures, which are microbes associated with foods as food fermentation agents, or starter cultures, but have not necessarily been tested for health effects. Some live active cultures, however, have demonstrated health effects, and can be called probiotics. Thus, despite potential overlap, these terms are not synonymous. Additionally, probiotics are not native commensal bacteria from humans, although they are commonly isolated from this source. Once they are shown to have health effects when administered to humans, members of our normal, commensal bacteria can be called probiotics. Another key concept essential to understanding probiotics is that the effects of these agents are strain-, not genus-, specific. Despite the range of potential health benefits observed with probiotics, the effects described can only be attributed to the strain or strains tested, and not to the group of probiotics as a whole.
- The dose of probiotics is usually expressed as the number of colony forming units (CFUs), or the number of viable microbe, per serving. The required dose of probiotics may vary greatly for different strains and the specific health effect under investigation, with health benefits ranging from 50 million to more than 1 trillion CFU/day. Further, dose-response studies regarding probiotics are not common. Thus, probiotic effects should be considered dose-specific, and it is not possible to make general recommendations about the minimum dose of probiotics that is needed for an effect. Accordingly, studies documenting the efficacy of specific strains at a specific dosage cannot be used as evidence to support health effects at a lower dosage, and the dose listed on the label must be based on studies that show a health effect in humans.
- Long term safety in at-risk individuals Long-term safety to be evaluated for: Translocation Case reports of endocarditis and abscesses Systemic sepsis Ulcerative colitis Crohn’s disease Utrecht pancreatitis Increased mortality in probiotic group Mesenteric ischemia
- Like their health effects and dosage, the safety of probiotics should be considered to be strain-specific. The genus and species of the microbe being used should be assessed with respect to genetic stability, metabolic activities, and the potential for pathogenicity or toxicogenicity. Additional factors important for assessing the safety of a probiotic include the method of administration, the level of exposure, the health status of the users, and the physiologic functions they are intended to perform. In general, few correlations between probiotic use and adverse events have been demonstrated; however, few studies have specifically addressed the safety of these probiotics. Commenting on this observation, Dr. Sanders added that “health care professionals are “extremely receptive to safe interventions, those they feel are associated with possible benefit without being a risk. Consumers should also understand that although probiotics marketed as foods and dietary supplements should be safe for the generally healthy population, their safety has not been asserted on individuals with underlying health conditions. So since dietary supplements do not undergo a preapproval for safety by the FDA; assurance of safety is the responsibility of product manufacturers. A health care professional should be consulted before using probiotics for young infants or people with compromised immune systems or other major underlying illnesses.
- The US government regulates dietary supplements on the basis of the Dietary Supplement Health and Education Act (DSHEA) of 1994, which was enacted to provide the legal framework specifically for dietary supplements. This regulation allows for structure/function claims and claims of general well-being. Most supplements currently on the market make structure/function claims, which describe the role of the dietary ingredient intended to affect a structure or function in humans. Examples of such claims on probiotics include those suggesting that the product “supports a healthy immune system,” “helps keep your microflora in balance,” or “helps build and maintain a healthy digestive system.” Thus, structure/function claims should “promote, support, maintain a healthy body system” rather than claim that the product can treat, cure, or prevent a disease. Under DSHEA, structure/function claims must be accompanied by the disclaimer that “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” Regardless of the nature of the claims they should be truthful and substantiated by scientific evidence.
- Most supplements currently on the market make structure/function claims, suggesting that the product “supports a healthy immune system,” “helps keep your microflora in balance,” or “helps build and maintain a healthy digestive system.” These claims are intended to promote, support and maintain a healthy body system. Under DSHEA, structure/function claims must be accompanied by the disclaimer that “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” Despite this required disclaimer and although structure/function claims do not require pre-approval from the FDA, the manufacturer is responsible for the accuracy and truthfulness of all claim(s).
- In conclusion, the intestinal flora may impact health through a number of protective, structural, and metabolic functions. Although these mechanisms have not been fully characterized, probiotic bacteria are believed to confer health benefits by bolstering these effects. However, it is essential to understand that not all probiotics are created equal, as the benefits of these agents are both strain-specific and dose-specific. Although the range of probiotic products is expanding, making clinical recommendations can be complicated by misinformation as well as the frequent disconnect between scientific evidence and allowable claims on these products. Consumers and health care professionals choosing probiotics should ensure that the health claim(s) regarding the product are substantiated with well-controlled studies and that the product has been adequately characterized for content and stability.