LET S TALK BUGS! THE ROLE OF PROBIOTICS IN PATIENT HEALTH AND DISEASE PREVENTION Dragana Skokovic-Sunjic RPh BScPhm NCMP
OUTLINE After the presentation, pharmacists will be able to: 1. Review and discuss micro-ecology of the intestinal tract, mechanism of action of probiotics and identify clinical evidence for probiotic supplements 2. Understand the role of probiotic interventions according to the evidence of specific probiotic strain for specific symptoms 3. Differentiate between probiotic supplements currently available in the pharmacy 4. Assess safety and potential adverse effects of probiotic products
PRESENTER DISCLOSURE Presenter s Name: Dragana Skokovic-Sunjic I have no potential or perceived conflict of interest I have relationships with: AEProbio (Alliance for Education in Probiotics) - Author, Advisory Board Clinical Pharmacist at Hamilton Family Health Team
DISCLAIMER While it is best practice to use generic names in educational programs, this presents a problem when a formulation is being discussed and not an active molecule. In the case of probiotics, the clinical evidence only supports certain formulations/brand names of the probiotics (including the genus, species, alphanumeric designation, number of live bacteria present, the blend of probiotic strains present, and finally the non-active ingredients present). As a result, I have used brand names in this program to provide a more practical learning experience. No bias is intended toward any one formulation
TERMINOLOGY: OLD AND NEW Microflora: in the past bacteria were classified in the Plant Kingdom; it is not an accurate term and has been increasingly substituted with "microbiota" Microbiome: the ecological community of all live microorganisms and their genes that literally share our body space Microbiota: the microorganisms of a particular site or the microscopic flora and fauna of a region Ref: Merriam-Webster Medical Dictionary https://www.researchgate.net/post/what_is_the_difference_between_the_terms_microbial_flora_and_microbiota Photo curtesy of R. Johnstone; clipart by: K. Whiteford
WHAT ROLES DOES MICROBIOTA HAVE IN THE BODY? 1. Immune function 2. Direct action against pathogenic bacteria 3. Barrier function 4. Metabolic and anti-oxidative role 5. Potential anti-carcinogenic action
MICROBIOTA OR WHERE THOSE BUGS CAME FROM? v The intestines of an infant were believed to be sterile at birth v Within hours they become colonized by bacteria v By age of 3-5 years we form our own unique fingerprint of diverse bacteria in the gut Photo credit: http://insertmedia.office.microsoft.com
FACTORS AFFECTING DEVELOPMENT OF HEALTHY MICROBIOTA EARLY IN LIFE v Mode of delivery vaginal vs Cesarean section v Feeding practices breast milk provides bacteria and specific oligosaccharides that encourage colonization by beneficial bacteria v Environment, caregivers Photo source : www.sacredmaternity.com
MICROBIOTA IMBALANCE WHY IT HAPPENS? Extinction events: - Hygiene hypothesis - preventing proper colonization - Missing microbiota hypothesis- disturbing proper colonization across generations Antibiotic use: - Average person in US will receive 10-20 courses of antibiotics by age 18 Physical or emotional stress Western diet: - Rich in refined carbohydrates - Low in fermented foods, complex carbs, fibre Infections Hawrelak JA, Myers SP. Altern Med Rev 2004;9(2)180-197.
PROBIOTICS Definition: live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Hill, C. ISAPP consensus on the probiotic concept, Gut Microbiota for Health World Summit, Barcelona March 2015
SOME OF THE INDICATIONS FOR USE OF PROBIOTICS ü Acute infectious diarrhea in children and adults ü Prevention of necrotizing enterocolitis (newborn, premature) ü Prevention of atopic dermatitis in children ü Prevention of relapse for ulcerative colitis ü Prevention of ventilator associated pneumonia (VAP) ü Prevents antibiotic associated diarrhea (AAD) ü Prevents recurrent C. difficile infections (CDI) ü Treatment of the common cold ü Reducing cholesterol levels ü Treatment/prevention of yeast infections ü Prevention of urinary tract infections
EXAMPLE OF DIFFERENT EFFECTS OF THE SAME GENUS AND SPECIES OF BACTERIA Genus: Escherichia Strain: Nissle 1917 Demonstrated benefits in IBD Species: coli Strain: H1 SE15 Harmless, commensal strain of E.coli Strain: H7 EDL 933 Extremely harmful Enterohemorrhagic strain of E.coli
DO PRODUCTS WITH MORE STRAINS OR HIGHER DOSE PROVIDE ENHANCED BENEFITS? Mix of strains greater effect Higher dose better dose ISAPP (International Scientific Association for Probiotics and Prebiotics, 2009 Report Photo source: https://dreastime.com
PROBIOTICS AND ANTIBIOTIC-ASSOCIATED DIARRHEA One of the most commonly reported adverse reactions during and/or after antibiotic therapy Incidence 5% - 39% depending the individual, prescribed antibiotic, duration of the treatment and the dose Diarrhea can occur up to 8 weeks after the end of the antibiotic therapy Hogenauer C, et al. Clinical Infectious Disease. 1998, 27(4):702 710. CPS, CPhA 2008- Individual Monographs
EXAMPLES OF PROBIOTICS CLINICALLY TESTED IN AAD Probiotic strain Dose used Brand and strength L. reuteri DSM 17938 0.4 billion/day 0r 5 drops per day BioGaia 100 million CFU L. acidophillus CL1285 L. casei Lbc80r L. rhamnosus CLR2 (synergists) 50 billion/day 60 billion/day 1-2 tubs per day Beausoleil et al. 2007 Bio-K+ CL1285 30 or 50 billion CFU L. casei DN 114001 2X10 billion/day 2 drinks per day Hickson et. al. 2007 DanActive drink 10 billion per serving Sacharomyces bouldardii (yeast) 2 X 250 mg/day 4 X 250 mg/day 2-4 doses per day Can et al. 2006 Florastor 5 bilion CFU (250 mg)
DIAGNOSIS OF IBS Rome Criteria III: Symptoms of recurrent abdominal pain or discomfort* and marked change in bowel habits, with symptoms experienced at least 3 days/month in the last 3 months** *Discomfort = an uncomfortable sensation not described as pain **For the last 3/12 with symptoms onset at least 6/12 prior to diagnosis Longstreth, G.F., et.al. Functional Bowel Disorders. Gastroenterology 130:1480-1491 (2006) http://ibdcrohns.about.com/cs/ibs/a/romecriteria.htm 16
DIAGNOSIS OF IBS Rome Criteria III (cont d) 2 or 3 of the following must apply: - Pain is improved with defecation - Onset related to a change in frequency of stool - Onset related to a change in appearance of stool Longstreth, G.F., et.al. Functional Bowel Disorders. Gastroenterology 130:1480-1491 (2006); http://ibdcrohns.about.com/cs/ibs/a/romecriteria.htm 17
PREVALENCE Affects up to 20% of adults - Affects about 5 million Canadians - One the of the most common disorders diagnosed by health care providers but not satisfactorily treated Females outnumber males Onset of symptoms usually seen < 35 years of age
IBS AND QUALITY OF LIFE (QOL) Interferes with daily activities and leisure time Affects sleep, diet, ability to travel and sexual functioning Affects ability to function in family and work-related roles Contributes to lost productivity and work absenteeism Hulisz, D. The Burden of Illness of Irritable Bowel Syndrome: Current Challenges and Hope for the Future. J Manag Care Pharm. 2004;10(4):299-309
WHY USE BACTERIA FOR IBS? Abnormality in the gastrointestinal microbiota in IBS patients Ratio of good bacteria vs. bad bacteria reversed compared to healthy individuals Reduced levels of good bacteria such as Lactobacilli and Bifidobacteria 1 Higher numbers of coliforms as well as an increased aerobe: anaerobe ratio 2 Re-colonizing the gut with beneficial bacteria can correct the abnormality and reverse the symptoms 1.Balsari A et al. The fecal microbial population in the IBS. Microbiologica. 1982 Jul;5(3):185-94. 2. Mättö J et al. Composition and temporal stability of gastrointestinal microbiota in IBS -a longitudinal study in IBS and control subjects. FEMS Immunol Med Microbiol. 2005 Feb 1;43(2):213-22.
EXAMPLES OF PROBIOTICS IN IBS Product Microbial Strain Dose Activia probiotic yogurt Guyonnet et al 2007 B. (animalis) lactis CNCM I-2494 1B CFU bacteria per pot One to three pots daily Align capsules Whorwell et al 2006 O Mahony et al 2005 Bifidobacterium infantis 35624 1 B CFU per capsule One capsule daily TuZen capsules Niedzielin et al 2001 Lactobacillus plantarum 299v 10 B CFU per capsule 1-2 capsules daily
PROBIOTICS IN DIABETES v Direct effect via alteration of microbiota v Indirect effect via changes in fermentation v Indirect effect via optimizing metformin effect Clinical Guide for Probiotic Products in Canada 2015 new indication added: lowering BG and HbA1c (B. lactis BB-12 and L. acidophilus LA-5 combination)
PROBIOTIC COMBINATION LA-5 AND BB-12 IN YOGURT FORM (YOPTIMAL AND IOGO PROBIO ) v Patients with Type II diabetes consumed 3 serving per day v Results: fasting blood glucose and HbA1c reduced significantly compared to control group Ejtahed H. et al Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 2012 May;28(5):539-43.
EXAMPLES OF PROBIOTICS IN COMMON INFECTIOUS DISEASE Product Microbial Strain Dose UltraFlora Cold Support Berggren et al 2011 Busch et al 2013 BioGaia drops/chewtab Weizman et al 2005 Gutierrez-Castrellon et al 2014 L plantarum HEAL9 L. paracasei 8700:2 0.5x10 7 CFU per capsule L. reuteri DSM 17938 100M CFU per capsule One capsule daily One tab or 5 drops daily HMF Fit for School Chewable tablet Garaiova et al 2015 DanActive Guillemard et al 2009, 2010 Marcos et al 2004 Mayer et al 2006 Ortiz-Andrellucchi et al 2008 L. acidophilus CUL21 L. acidophilus CUL60 B. lactis CUL34 B. bifidum CUL20 12.5 B CFU per tablet L. casei sp. Paracasei CNCM I-1518 10B CFU per bottle 1 tab daily 1-2 bottles per day
SAFETY OF PROBIOTICS Most commercially available probiotic strains are safe: use in healthy individuals does not increase the risk of bacterial diseases infections due to Lactobacillus and Bifidobacterium strains are extremely rare Common side-effects are transient: bloating, diarrhea, constipation, nausea & gastric discomfort Risk factors for probiotic sepsis: immuno-compromised (debilitated state or malignancy) central venous catheter Boyle R et al. American Journal of Clinical Nutrition. 2006; 83(6):1256-64 Morais MB et al., The role of probiotics and prebiotics in pediatric practice J Pediatr (Rio J). 2006 Nov;82 (5 Suppl):S189-97. Review.
ALLIANCE FOR EDUCATION IN PROBIOTIC Distribution and dissemination of Clinical Guide - available as a printed booklet - available online at: www.probioticchart.ca - available as PROBIOTIC mobile app