PROBIOTICS. Prof Kerryn Phelps 2012

Transcription

1 PROBIOTICS Prof Kerryn Phelps 2012

2 PROBIOTICS A probiotic has been defined as a live microbial feed supplement that beneficially affects the host by improving its intestinal microbial balance. Isolauri E et al. Probiotics: effects on immunity Am J Clin Nutr 2001;73(suppl):444S- 50S

3 Therapeutic Criteria for Probiotics The criteria for a microorganism to be defined as probiotic: the strain needs to be of human origin, be safe for human use, be stable in acid and bile, and adhere to the intestinal mucosa. Isolauri E et al. Probiotics: effects on immunity Am J Clin Nutr 2001;73(suppl):444S-50S

4 PROBIOTICS Probiotics seem to change how the immune system reacts to invading microorganisms. They may compete with harmful bacteria or enhance the immune system. Also, they may help calm the immune system's overreaction in ways not fully understood. And they may help restore or maintain proper bacteria balance in the intestines, which can be upset by antibiotics or invading microorganisms. Mayo Clinic

5 SPECIFIC PROBIOTICS Lactobacillus acidophilus Bifidobacterium lactis Lactobacillus plantarum 299v Lactobacillus rhamnosus Saccharomyces boulardii

6 Lactobacillus acidophilus (NCFM strain) Decreases the risk of infection Decreases the risk of allergy Enhances innate immune response Enhances the production of IL-1, IL-6, IL-12, INF, TNF Enhances phagocytosis in macrophages NCFM Lactobacillus Acidophilus is acid and bile resistant and rapidly repopulates the intestine and adheres to the gut wall

7 Bifidobacteria Bifidobacteria such as Bifidobacterium lactis (BBL), comprise approximately 90% of the endogenous beneficial bacteria in the mature large intestine. In breast-fed infants Bifidobacteria account for 99% of the endogenous beneficial flora.

8 Bifidobacteria Stimulate the endogenous production of acetic acid, lactic acid, and hydrogen peroxide Inhibit the growth of many pathogenic bacteria,including Bacillus cereus, Eschericia coli, Salmonella spp., Shigella dysenteriae, Staphylococcus aureus, Listeria spp.,campylobacter spp., Vibrio cholerae Promote the synthesis of several "B" vitamins (including biotin) within the intestinal tract. Stimulate B-Lymphocytes

9 Lactobacillus Plantarum 299v L. plantarum is commonly found in many fermented food products including sauerkraut, pickles, brined olives, Korean kimchi, Nigerian ogi, sourdough bread, and other fermented plant material, and also some cheeses Along with promoting normal digestive health, Lactobacillus plantarum has been shown to be an effective treatment for irritable bowel syndrome (IBS), Crohn s disease, and colitis. Antibiotic resistant Produces L-lysine

10 Lactobacillus rhamnosus GG Lactobacillus rhamnosus GG (ATCC 53103) is a strain of L Rhamnosus isolated in 1983 from the intestinal tract of a healthy human.; filed for patent in 1985 by Sherwood Gorbach and Barry Goldin (GG is from the forst letters of their surnames) Useful in allergy and eczema, and prevention of diarrhoea and respiratory infection

11 Saccharomyces boulardii Saccharomyces boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard after seeing it used in Southeast Asia to treat the symptoms of cholera. S. boulardii has been shown to maintain and restore the natural flora in the large and small intestine; it is classified as a probiotic. There are numerous randomized, double-blind placebocontrolled studies showing the efficacy of S. boulardii in the treatment and prevention of gastrointestinal disorders

12 WHAT IS A PREBIOTIC? Prebiotics are food ingredients that escape digestion, reach the large intestine and selectively stimulate the growth and/or activity of bacteria that are believed to be beneficial to health, such as bifidobacteria and lactobacilli Typically, they are oligosaccharides (eg oligofructose and inulin) The most common forms are classified as soluble fibre

13 Colostrum Natural source of immunoglobulins which protect the newborn and provide passive immunity. Contains: IgA, IgM and IgG Bioactive growth factors Lactoglobulin, lactalbumin

14 Immune activity of Bovine Colostrum Bovine colostrums are the "early" milk produced by cows during the first several days post-parturition. It has a nutrient profile and immunological composition that differs substantially from "mature" milk. Included in the nutrient profile are higher amounts of immunoglobulins, growth factors, cytokines, and nucleosides than are found in milk. Bovine colostrums are also rich in oligosaccharides, antimicrobials, and immune-regulating factors. Available evidence suggests a beneficial effect of supplementation of bovine colostrums in improving body composition, aspects of athletic performance, diarrhea in persons with immune-deficiency syndromes, NSAID-induced gastrointestinal disturbances, and aspects of the acute phase response that occurs secondary to surgery. Kelly GS. Bovine colostrums: a review of clinical uses. Altern Med Rev Nov;8(4):378-94

15 Potential uses of colostrum Immunoglobulins, growth factors and antimicrobial peptides (lactoferrin and lactoperoxidase) in colostrum may be useful in the treatment of a wide range of gastrointestinal disorders including inflammatory bowel disease, NSAID-induced gut damage, chemotherapy-induced colitis, and dysbiosis and diarrhoea.

16 When to Recommend Specific Probiotics Antibiotics Other medications (OCP, cortisone) Acute diarrhoeal illness Gut inflammation IBS Helicobacter pylori infection Healthy immune function (especially children & elderly) Allergy Vaginal candidiasis Halitosis, oral health, caries and gingivitis?

17 ANTIBIOTICS Antibiotics are the most common and significant cause of disturbances in the normal gastrointestinal flora Symptoms include: diarrhoea nausea A more serious form of colitis called pseudomembranous colitis can cause abdominal pain, fever and bloody diarrhea. S. Boulardii the favoured probiotic for prevention and treatment Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebocontrolled trial. Aliment Pharmacol Ther Mar 1;21(5):

18 Prevention of Pediatric Antibioticassociated Diarrhoea Probiotics show promise for the prevention of pediatric AAD. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.

19 Prevention of antibioticassociated diarrhoea A meta-analysis of nine randomised, double-blind, placebo controlled trials of probiotic organisms published in BMJ Conclusions: The meta-analysis suggests that probiotics can be used to prevent antibiotic associated diarrhoea and that S boulardii and lactobacill rhamnosus have the potential to be used in this situation. D Souza AL, et al. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324;8 June 2002.

20 COCHRANE REVIEW ON AAD Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven Cochrane Database Syst Rev Nov 9;11:CD Probiotics for the prevention of pediatric antibiotic-associated diarrhea

21 PROBIOTIC BACTERIA HELP TO IMPROVE LACTOSE INTOLERANCE The majority of the world s population is lactose intolerant. Lactobacilli produce the enzyme lactase, and may improve lactose intolerance in milk-sensitive infants and children. Shermak MA, Saavedra JM, Jackson TL, Huang SS, Bayless TM, Perman JA. Effect of yogurt on symptoms and hydrogen production in lactose-malabsorbing children. Am J Clin Nutr 1995;62:

22 Effect of Lactobacilli on paracellular permeability in the gut Abstract Paracellular permeability is determined by the complex structures of junctions that are located between the epithelial cells. In 1996, it was shown that the human probiotic strain Lactobacillus plantarum 299v and the rat-originating strain Lactobacillus reuteri R2LC could reduce this permeability in a methotrexate-induced colitis model in the rat. Subsequently, many animal models and cell culture systems have shown indications that lactobacilli are able to counteract increased paracellular permeability evoked by cytokines, chemicals, infections, or stress. There have been few human studies focusing on the effect of lactobacilli on intestinal paracellular permeability but recently it has been shown that they could influence the tight junctions. More precisely, short-term administration of L. plantarum WCSF1 to healthy volunteers increased the relocation of occludin and ZO-1 into the tight junction area between duodenal epithelial cells. Ahrne S, Hagslatt ML.Effect of lactobacilli on paracellular permeability in the gut. Nutrients Jan;3(1): Epub 2011 Jan 12.

23 Probiotics: immunomodulation of local and systemic immune response Isolauri E et al. Probiotics: effects on immunity Am J Clin Nutr 2001;73(suppl):444S-50S

24 Irritable Bowel Syndrome Typically begins in early adult life Believed to affect approximately one-fifth of the population Estimated that % of symptomatic people do not seek medical attention. Typical symptoms include abdominal pain, excessive flatus and variable bowel habit Madden JA, Hunter JO. A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics. Br J Nutr Sep;88 Suppl 1:S67-72.

25 IRRITABLE BOWEL SYNDROME IBS Constipation Dominant Diarrhoea Dominant Pain Gas Bloating

26 Irritable Bowel Syndrome The prevalence of IBS is 3-4 times greater in women than men Female patients seem to have more frequent and severe symptoms and they seek health care more often. The prevalence of IBS declines with age. Mach T. The brain-gut axis in irritable bowel syndrome-clinical aspects. Med Sci Monit 2004;10(6):RA

27 L. plantarum 299v Improves IBS Probiotic therapy using Lactobacillus plantarum 299v has demonstrated superiority to placebo in improving pain, regulating bowel habits, and decreasing flatulence in irritable bowel syndrome. Sach JA, Chang L. Irritable Bowel Syndrome. Curr Treat Options. Gastroenterol 2002 Aug;5(4):

28 A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome Forty patients were randomized to receive either LP299V in liquid suspension (20 patients) or placebo (20 patients) over a period of 4 weeks. Results All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group (P ). There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo (P 0.17). With regards to all IBS symptoms an improvement was noted in 95% of patients in the LP299V group vs 15% of patients in the placebo group ( P < ). Niedzielin K; A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome European Journal of Gastroenterology & Hepatology 2001, 13:1143±1147

29 Helicobacter pylori infection Seven of 9 human studies showed an improvement of H. pylori gastritis and decrease in H. pylori density after administration of probiotics. The addition of probiotics to standard antibiotic treatment improved H. pylori eradication rates (81% vs. 71%, with combination treatment vs. H. pylorieradication treatment alone;. Probiotic treatment reduced H. pylori therapyassociated side effects (incidence of side effects: 23% vs. 46%, with combination therapy vs. H. pylorieradication treatment alone. Lesbros-Pantoflickova D, Corthésy-Theulaz I, Blum AL. Helicobacter pylori and probiotics. J Nutr Mar;137(3 Suppl 2):812S-8S.

30 THERAPEUTIC USES FOR S. Boulardii Acute diarrhea Two studies each showed a significant reduction in the symptoms of acutegastroenteritis in children, versus placebo, by measuring frequency of bowel movements and other criteria. Children over three months are recommended to take two doses of 250 mg a day (BID) for five days to treat acute diarrhea. Children under three months are recommended to take half a 250 mg capsule or sachet twice daily for five days. A prospective placebo-controlled study found a significant reduction in symptoms of diarrhea in adults as well taking 250 mg of S. boulardii twice a day for five days or until symptoms are relieved Höchter W, Chase D, Hagenhoff G (1990). "Saccharomyces boulardii in acute adult diarrhoea. Efficacy and tolerance of treatment". Münch Med Wochenschr 132:

31 Antibiotic-associated diarrhea :There is evidence for S Boulardii use in the prophylactic treatment of antibiotic-associated diarrhea (AAD) in adults. There is further evidence for its use to prevent AAD in children. McFarland LV, Surawicz CM, Greenberg RN et al (1995). "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo". Am. J. Gastroenterol. 90 (3): ^ Kotowska M, Albrecht P, Szajewska H (2005). "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial". Aliment. Pharmacol. Ther. 21 (5):

32 Irritable bowel syndrome A prospective placebo-controlled study found patients with diarrhea predominant irritable bowel syndrome (IBS) had a significant reduction on the number and consistency of bowel movements. Maupas J, Champemont P, Delforge M (1983). "Treatment of irritable bowel syndrome with Saccharomyces boulardii: a double blind, placebo controlled study". Medicine Chirurgie Digestives 12 (1): 77 9.

33 Travellers' diarrhoea Austrian vacationers taking S. boulardii traveling around the world were found to have significantly fewer occurrences of travelers' diarrhea than those taking placebo. The more S. boulardii taken in prevention, starting five days before leaving, the higher the reduction in diarrhea reported. The reduction was also found to be dependent upon where the vacationer traveled.[11] The recommended dosage is one 250 mg capsule or sachet per day (QD). Kollaritsch H, Kemsner P, Wiedermann G, Scheiner O (1989). "Prevention of traveler's diarrhoea. Comparison of different non-antibiotic preparations". Travel Med Int: 9 17.

34 Recurrent Clostridium difficile infection Administration of two 500 mg doses per day of S. boulardii when given with one of two antibiotics (vancomycin or metronidazole) was found to significantly reduce the rate of recurrent Clostridium difficile (pseudomembranous colitis) infection. No significant benefit was found for prevention of an initial episode of Clostridium difficile-associated disease.

35 HEALTHY IMMUNE RESPONSES IN OLDER AGE The aging process can lead to a decline in cellular immunity. Subjects aged Increases in the proportions of total, helper (CD4(+)), and activated (CD25(+)) T lymphocytes and natural killer cells were measured in the subjects' blood after consumption of B. lactis HN019. The ex vivo phagocytic capacity of mononuclear and polymorphonuclear phagocytes and the tumoricidal activity of natural killer cells were also elevated after B. lactis HN019 consumption. The greatest changes in immunity were found in subjects who had poor pretreatment immune responses. Gill HS, et al. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr 2001 Dec;74(6):833-9.

36 Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Hojsak I, Abdović S, Szajewska H, Milosević M, Krznarić Z, Kolacek S. Pediatrics 2010 May;125(5):e Epub 2010 Apr Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, Zagreb, Croatia. The incidence of nosocomial infections, predominantly gastrointestinal and respiratory, in children in developed countries is high, ranging from 5% to 44%. There is no effective strategy for preventing these infections. METHODS: A randomized, double-blind, placebo-controlled trial of 742 hospitalized children were randomly allocated to receive for their hospitalization LGG at a dose of 10(9) colony-forming units in 100 ml of a fermented milk product (LGG group, n = 376) or placebo that was the same postpasteurized fermented milk product without LGG (placebo group, n = 366). RESULTS: In the LGG group, compared with the placebo group, we found a significantly reduced risk for gastrointestinal infections (relative risk [RR]: 0.40 [95% confidence interval (CI): ]; number needed to treat: 15 [95% CI: 9-34)], respiratory tract infections (RR: 0.38 [95% CI: ]; number needed to treat: 30 [95% CI: ]), vomiting episodes (RR: 0.5 [95% CI: ]), diarrheal episodes (RR: 0.24 [95% CI: ]), episodes of gastrointestinal infections that lasted >2 days (RR: 0.40 [95% CI: ]), and episodes of respiratory tract infections that lasted >3 days (RR: 0.4 [95% CI: ]). Groups did not differ in hospitalization duration (P =.1). CONCLUSIONS: LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities.

37 Probiotic Effects on Cold and Influenza- Like Symptom Incidence and Duration in Children D-B, P-C study, 326 eligible children (3 5 years of age) assigned randomly to receive placebo (N = 104), Lactobacillus acidophilus NCFM (N = 110), or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 (N = 112). Children were treated twice daily for 6 months. RESULTS: Relative to the placebo group, single and combination probiotics reduced fever incidence by 53.0% and 72.7%, coughing incidence by 41.4% and 62.1%, and rhinorrhea incidence by 28.2%, respectively. Fever, coughing, and rhinorrhea duration was decreased significantly, relative to placebo, by 32% (single strain) and 48% (strain combination). Antibiotic use incidence was reduced, relative to placebo, by 68.4% (single strain) and 84.2% (strain combination). Subjects receiving probiotic products had significant reductions in days absent from group child care, by 31.8% (single strain) and 27.7% (strain combination) CONCLUSION: Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever, rhinorrhea, and cough incidence and duration and antibiotic prescription incidence, as well as the number of missed school days attributable to illness, for children 3 to 5 years of age. Leyer G et al. Pediatrics Vol. 124 No. 2 August 1, 2009

38 A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years DBRP-C Trial (Australian New Zealand Clinical Trials Registry: ACTRN )showed that in a high risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus (HN001) (6 x 10 9 cfu/day) halved the cumulative prevalence of eczema at 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 x 10 9 /cfu day) had no effect. Conclusions and Clinical Relevance This study showed that the protective effect of Lactobacillus rhamnosus against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants. Wickens K et al A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years Epidemiology of Allergic Disease.

39 ALLERGY AND BACTERIAL COLONISATION Bacterial colonisation of the colon shortly after birth : appropriate microbiological stimuli essential to redress the balance of the skewed T-helper immune response present in the newborn. The normal interaction between infant and microbes is thought to be compromised in the Western world, with reduction in bifidobacteria and increase in clostridial species, especially in bottle fed infants. Furrie, E. Probiotics and allergy Proceedings of the Nutrition Society (2005), 64,

40 PROBIOTICS AND ALLERGY The use of probiotic therapy to prevent allergic disease has been demonstrated in two studies using a probiotic Lactobacillus rhamnosus GG in neonates. A long-term reduction in allergy has been shown in the test group, with lactobacillus reducing the incidence of atopic eczema. Management of allergy through probiotics has also been demonstrated in infants, using lactobacilli to control atopic eczema and cow s milk allergy. Unfortunately, these positive results have not been repeated in studies with older children and young adults. Furrie, E. Probiotics and allerg.y Proceedings of the Nutrition Society (2005), 64,

41 Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among lowatopy-risk infants Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Conclusion: Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.

42 PROBIOTICS AND CARDIOVASCULAR RISK In hypercholesterolemic patients supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen. Results: Significant decreases in systolic blood pressure (P < 0.000), leptin (P < 0.000), and fibrinogen (P < 0.001) were recorded in the experimental group. No such changes were observed in the control group. Conclusion: L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers. Naruszewicz N et al Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. American Journal of Clinical Nutrition, Vol. 76, No. 6, , December 2002

43 Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis 120 healthy Chinese women with a history of recurrent BV were assigned randomly to daily vaginal prophylaxis with 1 capsule (Probaclac Vaginal; Nicar Laboratories, Inc, Blainville, Quebec, Canada) containing 8 billion colony-forming units of Lactobacillus rhamnosus, L acidophilus, and Streptococcus thermophilus (n = 58 women) or 1 placebo capsule (n = 62 women) for 7 days on, 7 days off, and 7 days on. Results: Probiotic prophylaxis resulted in lower recurrence rates for BV (15.8% [9/57 women] vs 45.0% [27/60 women]; and Gardnerella vaginalis incidence through 2 months (3.5% [2/57 women] vs 18.3% [11/60 women]). Between the 2- and 11-month follow-up period, women who received probiotics reported a lower incidence of BV and G vaginalis. Only adverse events were vaginal discharge and malodor. Conclusion : Short-term probiotic prophylaxis is well tolerated and reduces BV recurrence and G vaginalis risk through 11 months after treatment. Wang Ya, Reifer C Miller LE, American Journal of Obstetrics & GynecologyVolume 203, Issue 2, Pages 120.e1-120.e6, August

44 When will it start to work Probiotics can start to exert beneficial effects in digestive disorders within a few days. Long-term benefits are seen after weeks to months of continuous use. Greater results may be obtained if the prebiotics are added

45 PRESENTATION Probiotic supplements come in capsules, tablets and powders. While exact doses haven't been determined, the general consensus is that a daily dose of about 10 billion colony-forming units is needed to provide benefits.

46 Safety Issues There have been no reports of probiotics interacting with prescription medication There is a slight chance that probiotics might cause pathological infection, particularly in severely immunocompromised patients. Probiotic strains of Lactobacillus have also been reported to cause bacteremia in patients with short-bowel syndrome, possibly due to altered gut integrity S. boulardii is contraindicated in patients with a yeast allergy