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Probiotics and prebiotics related to pharmacology


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Probiotics and prebiotics related to pharmacology

  1. 1. Probiotics, Prebiotics: Emerging importance in Pharmacology
  2. 2. Overview of Presentation • Introduction • History • Facts about intestine • Probiotics • Definition • Criteria • Mechanism of action • Safety issues • Assosiated benefits • Drug interactions • Precautions & contraindications • Prebiotics • Definition • Criteria • Mechanism of action • Potential benefits • Assosiated risks • Clinical applications • Regulatory guidelines • Challenges • Postbiotics, synbiotics etc. • Conclusion
  3. 3. Introduction • Quality healthcare is the foundation of any prosperous nation. • Long before the existence of microorganisms was known or recognized, fermented products were used therapeutically, to treat colds, fevers, and ailments of the gastro intestinal tract such as constipation and diarrhea. • Research has shown that Probiotics and Prebiotics are useful in achieving positive health effects and well being to the host. • It however gained momentum only recently. • India is also fast emerging as a potential market for these. • Probiotic product industries in India were estimated to be around Rs 20.6 million with a projected annual growth rate of 22.6% until 2015
  4. 4. Intestine is a paradise of disease “Death sits in the bowels; a bad digestion is the root of all evil” - Hippocrates, ca. 400 BC
  5. 5. History of Probiotics - 1900’s • At the start of the 20th century, Russian Nobel prize winner and father of modern immunology, Elie Metchnikoff, a scientist at the Pasteur Institute, was the first to hypothesised that consuming large amounts of fermented milk products that contained Lactobacillus bacteria (“soured milk”) could prolong and improve the quality of life.
  6. 6. History contd. • In early 1930’s, in Japan, Minoru Shirota developed a fermented milk product called Yakult with a special strain of Lactobacillus casei shirota • The word “probiotic” (origins: Latin pro meaning “for” and Greek bios meaning “life”) was first used in 1954 to indicate substances that were required for a healthy life • Probiotics term coined in 1965 by Lilly And Stillwell • Japanese were the first to recognise the value of non-digestible oligosaccharides • It was not until 1995 that the scientific concept for human gut microbiota modulation by “prebiotics” was introduced
  7. 7. • It participates in protection of the host through strong defense mechanisms from the external environment • Defense task is based on three barriers: • 1- The ecological barrier (normal inhabitant flora within intestine) • 2- Mechanical barrier (mucous epithelia) • 3- Immune barrier (GALT, secretory IgA, intraepithelial lymphocytes, macrophages, neutrophils, natural killer cells, Payer’s patches and mesenteric lymph nodes) • Our Intestine = 400 square meter surface… i.e. the surface area of a tennis court Largest immune organ
  8. 8. • Trillions living bacteria exist in the human intestine • We have more bacteria in our bodies (10 times greater) than the total number of our somatic and germ cells •  We carry about 2 kg of bacteria !!!!!!!! • Over 500 species of bacteria present in human colon. • Lactobacillus, Bifidis and Acidophilus comprise the majority of healthy bacteria in the colon along with other disease producing bacteria. • Normal ratio is 4:1. Facts about Intestine
  9. 9. • Dysbiosis is the abnormal microbial colonization of the intestine , where changes in quantity and quality of flora become pathological & harmful. • Common cause of dysbiosis: • Antibiotic therapy • Others are fast paced lifestyle, stress, food habits, chlorine in drinking water, Alcohol intake and cigarrete smoking • Age • Autoimmune conditions (rheumatoid), IBD etc. Dysbiosis
  10. 10. Terminologies • Prebiotics (before life)- A substance that cannot be digested but thus promote the growth of beneficial bacteria and probiotics. • Probiotics (for life)- live microorganisms which when administered in adequate amounts confer a health benefit on the host. • Synbiotics (plus life)- substance containing both above. • Antibiotics (against life)-A substance that can destroy or inhibit the growth of other microorganisms. Antibiotics are widely used in the prevention and treatment of infectious diseases.
  11. 11. Terminology • Biotherapeutic agent: A therapeutic material produced using biological means, including recombinant DNA technology eg. interferons, interleukins, and growth factors • Functional foods- defined as products that are similar in appearance to conventional foods that are consumed as part of a normal diet and have demonstrated physiological benefits, and/or have the potential to reduce the risk of chronic disease beyond nutritive function, i.e. they contain bioactive compounds.
  12. 12. • The term “Nutraceutical” was coined from “Nutrition” & “Pharmaceutical” in 1989 by Stephen De Felice, • Nutraceutical can be defined as “ A food or part of food or nutrient, that provides health benefits, including the prevention and treatment of a disease.” • Includes :- Engineered grain, cereals supplemented with vitamins or minerals, genetically manipulated soybean and canola oil without trans-fatty acids Nutraceuticals
  13. 13. Classification of nutraceuticals Based on chemical constituents: • Nutrients :- Substances with established nutritional functions, such as vitamins, minerals, amino acids and fatty acids • Herbals :- Herbs or botanical products as concentrates and extracts, such as aloe vera juice, evening primose oil • Dietary Supplement :- products that contain a dietary ingredient intended to add something to the foods we eat such as prebiotics, probiotics
  14. 14. Probiotics
  15. 15. Definition • Probiotics - live microorganisms which, when administered in adequate amounts, confer a health benefit on the host ( FAO/WHO 2001)
  16. 16. Characteristics of Effective Probiotics Probiotic microorganisms should be: • Able to Maintain good viability • Able to survive the passage through the digestive system • Must not deconjugate bile salts • Able to attach to the intestinal epithelia and colonize • Carry no antibiotic resistance genes that can be transferred to pathogens • Able to utilize the nutrients and substrates in a normal diet • Capable of exerting a beneficial effect on the host
  17. 17. • Produce Antimicrobial Compound • Organic acids • Hydrogen peroxide • Carbon dioxide • Diacetyl • Acetaldehyde • Bacteriocins • To be safe, noninvasive, noncarcinogenic and nonpathogenic • Coaggregate to form a normal balanced flora • Strain must not induce an immune reaction in the host
  18. 18. Levels of action
  19. 19. Mechanism of action (1) Competition for dietary ingredients as growth substrates, (2) Bioconversion of, for example, sugars into fermentation products (3) Production of growth substrates, for example vitamins, for other bacteria (4) Direct antagonism by bacteriocins (5) Competitive exclusion for binding sites (6) Improved barrier function (7) Reduction of inflammation, thus altering intestinal properties (8) stimulation of innate immune response (by unknown mechanisms)
  20. 20. Beneficial effects of probiotics • Immunological benefits- • Activate local macrophages to increase antigen presentation to B lymphocytes and increase IgA production locally • Modulate cytokine profile • Induce hyporesponsiveness to food allergies • Lower blood ammonia levels • Lower serum cholesterol levels • Produce vitamins eg: vitamin B,K, folic acid • Promote normalization of intestinal flora after antibiotic therapy • Act as immunomodulator- by promoting attacks on malignant cells
  21. 21. • Nonimmunologic benefits- • Digest food and compete for nutrients with pathogens • Alter local pH • Produce bacteriocin to inhibit pathogen • Scavange superoxide radical • Stimulate epithelial mucin production • Enhance intestinal barrier function • Compete for adhesion with pathogen • Modify pathogen derived toxins
  22. 22. Forms and Dosage of probiotics • Most common forms for probiotics are dairy products and probiotic-fortified foods • Formulations: drops, chewable tablets, lozenges, capsules, straws, bottle caps and bacteria in freeze-dried form are also available • Sporolac, ViBact, Darolac, Biglac, Bifilac etc. • Dose needed depending on the strain and product. • Over the counter dose is 1-10 billion cfu/dose • Bifidobacterium infantis for IBS-100 million cfu/dose
  23. 23. • Dose-Varies greatly with product • Live and active cultureYogurts must contain >108 [100 million] • L.rhamnosus GG has 10 billion • Duration: probiotics are taken daily for 2weeks to 2 months • Often taken empty stomach • If taken along with antibiotics, gap of 2 hrs.
  24. 24. Fecal microbiota transplantation (FMT) • FMT is the process of transplantation of fecal bacteria from a healthy individual into a recipient patient for the treatment of C. difficile infection. • The procedure can be carried out via enema (simplest and most acceptable) through the colonoscope, or through a nasogastric or nasoduodenal tube. • Most patients with C. difficile infection recover and have it eradicated after just one treatment.
  25. 25. Established Probiotics • The majority of probiotics are incorporated into dairy products such as milk powders, yoghurt, cheese and ice cream • Non-dairy products such as malt-based beverages and fruit juices meat sausages, capsules, and freeze-dried preparations. • Most common micro-organisms which are used:- BIFIDOBACTERIUM • Infantis (breastmilk) • lactis • longum • breve • Bifidum LACTOBACILLUS(first and largest group) • reuteri • casei • ramnosus • Acidophilus LACTOCOCCUS, SACCHAROMYCES, STREPTOCOCCUS,THERMOPHILUS, ENTEROCOCCUS
  26. 26. Drug Interactions • Concurrent administration of antibiotics could kill a large number of the organisms, reducing the efficacy of the Lactobacillus and Bifidobacterium species. Patients should be instructed to separate administration of antibiotics from these bacteria-derived probiotics by at least two hours. • S. boulardii might interact with antifungals, reducing the efficacy of this probiotic
  27. 27. Precautions and Contraindications • Critically ill or severely immunocompromised patients, probiotic strains of Lactobacillus have been reported to cause bacteraemia, endocarditis, meningitis. • Short-bowel syndrome can have bacteremia, possibly due to altered gut integrity. • Caution is also taken in patients with central venous catheters. • Lactobacillus preparations are contraindicated in persons with a hypersensitivity to lactose or milk. • S. boulardii is contraindicated in patients with a yeast allergy. • No contraindications are listed for bifidobacteria, since most species are considered nonpathogenic and nontoxigenic.
  28. 28. Prebiotics
  29. 29. Definition • Prebiotics are defined as nondigestible food ingredients (oligosaccarides) that are resistant to digestion and absorption , are fermented by cecal /colonic microbiota, and selectively stimulate growth and/or activity of bacteria that contribute to colonic and host health • Prebiotics; are simply speaking the preferential “FOOD” for Friendly Beneficial Bacteria colonizing the digestive tract. • They are dietary supplements that play a role in Balancing the Intestinal Mucosal Immune System Colonic food
  30. 30. Criteria for eligibility as prebiotics 1. Resistance to gastric acidity, to hydrolysis by mammalian enzymes, and to gastrointestinal absorption 2. Selective stimulation of the growth and/or activity of intestinal bacteria that contribute to health and well- being 3. Fermentation by intestinal microflora; to produce SCFA & gas. 4. Induce LUMINAL or SYSTEMIC beneficial effects. Gibson et al., 2007
  31. 31. Established prebiotics Name Obtained from/manufactured by Inulin Extraction from chicory root, Wheat, banana, onions, garlic, leek Fructo-oligosaccharides Tranfructosylation from sucrose, or hydrolysis of chicory inulin Galacto-oligosaccharides Produced from lactose by b-galactosidase, milk SOS (soy-oligosaccharides) Extracted from soya bean whey XOS (xylo-oligosaccharides) Enzymic hydrolysis of xylan IMO (isomalto oligosaccharides) Transgalactosylation of maltose Pyrodextrins Pyrolysis of potato or maize starch Breast Milk oligosaccharides Original they represent the third largest component of Human Milk 20 - 23 gm/l in colostrum & 12- 14 gm/ in mature milk Aliment Pharmacol Ther 24, 701–714
  32. 32. Potential prebiotics • Mannanoligosaccharides (yeast cell wall) • Glucooligosaccharides • Lactose • Arabinogalactan (radishes, carrots, tomatoes and wheat) • Polydextrose • Glucuronic acid • Sugar alcohols • Pectin oligosaccharides (apple pectin, citrus pectin) • Whole grains • gum arabic, guar gum • Potential applications for prebiotics as food ingredients to improve the gastrointestinal health include beverages, bakery products, table spreads, sauces, infant formulae and weaning foods, cereals, confectionery, snack bars, soups, salad dressings and dairy products
  33. 33. Mechanism of action • Mechanisms by which prebiotics provide health benefits • Increases the amount of lactic acid producing bacteria (lactobacilli and bifidobacteria) • Increases the amount of Short Chain Fatty Acids (SCFAs)- Butyrate, Acetate, Lactate etc… • Activates carbohydrate receptor immune cells Journal of Family Ecology and Consumer Sciences, Vol 35, 2007
  34. 34. Potential benefits 1. Fermentation of oligofructose in the colon results in a large number of physiologic effects • Increase mineral absorption( as they do not bind them) • Shortening gastrointestinal transit time • lowering blood lipid levels (decrease requirement of fat in food because of their gel like property) • Increasing fecal weight (decreases constipation) • The increase in colonic bifidobacteria has been assumed to benefit human health by • producing compounds to inhibit potential pathogens • reducing blood ammonia levels • producing vitamins and digestive enzymes.
  35. 35. 2. Production of short chain fatty acids (SCFA) eg: Acetate, Propionate, and Butyrate and Lactic acid • Increase water and sodium absorption • Increase mucosal blood flow and mucosal cell proliferation hence mucus production • Improvement of the epithelial barrier function (by regulating tight junction protein genes) • Promoting homeostatic immunoregulation by the induction of interleukin (IL)-10, transforming growth factor (TGF)-b and by the inhibition of tumor necrosis factor (TNF)-a and IL-12 synthesis • Prevent colon inflammation • Decrease lymphocyte proliferation • Inhibit C.K production • Induce T lymphocyte apoptosis • Activates G-Protein coupled receptors (supply fuel to immune cells)
  36. 36. Associated risks • Fructose malabsorption (with FOS & Inulin) • Can irritate GIT if taken in high dose and Ca+2 content is low (produced lactic acid irritates wall of intestine) • GI Disturbances: • Constipation/ Diarrhoea • Abdominal pain • Flatulence • Bloating This is advantageous as it allows a relatively broad “therapeutic window”
  37. 37. Forms and dosage • Ispaghula husk as a loose powder. A good dose is 10 grams (= 2 heaped teaspoons) twice daily. For IBS • FOS (fructooligosaccharides) loose powder. A good dose is 2.5 grams (= 1 level teaspoon) twice daily. • Inulin powder/syrups 2.5 grams (= 1 level teaspoon) twice daily (better prebiotic than FOS) • GOS (Galactooligosaccharides) 5 grams daily. • Butyric acid capsules- Provide most of the benefits of probiotics, without actually taking probiotics for upset of gut • Start with lower doses for a few days, otherwise may experienced some constipation. • Caution is taken with antibacterial herbs or supplements that are taken alongwith, which may inhibit the good bacteria as well as the bad. The Wonders of Prebiotic.Hip, Oct 6, 2010.
  38. 38. Clinical application of probiotics and prebiotics Proven Benefit • Diarrheal Illness (viral) - treatment and prevention • Prevention of antibiotic-associated diarrhea • Constipation Suggested Benefit • Food allergies • Inflammatory bowel disease • Lactose intolerance • Treatment of recurrent Clostridium dificile infection (Clostridium dificile is a bacteria that can cause serious infection in the intestine). • Eczema
  39. 39. Holds Promise • Cystic fibrosis • Dyslipidemia/ Cardiovascular dieases • Liver disease • Rheumatoid arthritis • Traveler’s diarrhea / bacterial enteritis • Vaccine immuno-augmentation • Genitourinary tract infections • Necrotising enterocolitis • Allergic rhinitis • Asthma • Attention deficit disorder (ADD) / Attention deficit hyperactivity disorder (ADHD) • Autism • Colic • Colon cancer prevention • Obesity
  40. 40. Treating Infection Antibiotic Associated Diarrhea • Associated with C.difficile which may cause pseudomembraneous colitis • Lactobacillus GG successful in eradicating C.difficile • Saccharomyces boulardii in DBC study reduced recurrence from 22% to 9.5% • Useful in reducing the severity and duration of acute infectious diarrhea in children • Probiotics used in prevention and as adjuvant therapy in AAD. Guandalini. J Clin Gastroenterol, 2008
  41. 41. Childhood diarrhea • Metanalysis revealed length of course of childhood diarrhea reduced 1–1.5 d, decreased frequency of infections, decreased shedding of rotaviruses or promotion of systemic or local immune response, increase in the production of rotavirus-specific antibodies when probiotic added to treatment • Probiotics given as suspended in oral rehydration solutions • By stimulating rotavirus specific IgA production of through B cells Traveller’s diarrhea • Incidence reduced from 71 to 43% in tourist study with S.boulardii Floch. JClinGastro 2005;40:275
  42. 42. Allergy • Atopic eczema, Dermatitis, Allergic rhinitis, Asthma, food allergies with milk, eggs, peanuts, tree nuts, soy, wheat gluten, fish, shellfish and shrimp • Atopic children tend to have a degree of dysbiosis, with more clostridia and fewer bifidobacteria •  IgE thought to be caused by a skewed balance between Th1 and T helper type 2 cells • Probiotics improving the Th1/Th2 balance in favour of a predominance of Th1 cells • Lactobacillus GG has been used to treat cow milk allergy and atopic eczema • prebiotic-supplemented infant formula reduce susceptibility to atopy but that the benefits persist up to 2 years of age
  43. 43. Genitourinary • Recurrent Candida Vaginitis and Bacterial Vaginosis have been successfully treated by administration of both oral and vaginal Lactobacilli • Vaginal suppositories with 1 billion cfu • Recent study in 185 Nigerian woman with vaginosis – L.rhamnosus + L.reuteri + metronidazole more effective than metronidazole alone – 88% to 40%* Floch. JClinGastro 2005;40:275
  44. 44. IBD • IBD is associated with a breakdown of the normal barrier function provided by the gut epithelial lining and its associated mucus commensal bacteria might be altered. • Use of probiotics and prebiotics giving good results in maintaining remission in UC but not of much in CD • Usually 1x109, or 1 billion colony forming units (CFU) is a good daily dose
  45. 45. IBS • Prebiotics relieve constipating symptoms- • Increased bacterial mass and osmotic water-binding capacity making stools bulky • Increased stool frequency and softer stools • Butyrate, have a positive effect on the endothelium and on peristalsis, which improves transit • A reduction in abdominal bloating and flatulence as a result of probiotic treatments is a consistent finding • some strains may ameliorate pain and provide global relief (B. infantis 35624), Lactobacillus reuteri may improve colicky symptoms within one week • 108 cfu of the freeze-dried probiotic bacteria B. infantis spec.
  46. 46. Prevention of Carcinogenesis & Tumor Growth • Prevention or delay in tumor development by lactobacilli • By binding to Mutagenic compound in the intestine & decreasing absorption of these mutagenic heterocyclic amines. • Lactobacillus (GG) decrease activity of following and helps to prevent procarcinogen to carcinogen • β glucoronidase • Nitroreductase • Cholylglycine hydrolase • SCFA like Butyrate is the preferred energy substrate for the colonocyte, it provides fuel (nutrition) for ileal and colonic epithelial cells, which help maintain the integrity of the colon. • Reduction in DNA damage and a reduction in cell proliferation in colon biopsies.
  47. 47. Immunoregulation • Probiotics helps to Increase IgA production by B- cells • Endowed with antiviral property, induce NO synthase (a virus infected cell death mechanism) • Production of gamma intereferon, TNF-alph,IL-1 by mononuclear cells incubated with Lactobacillus. Increase cytotoxic potential of NK cells, increasing IL-10 synthesis thus preventing acute infectious disease (nosocomial diarrhea in children, influenza episodes in winter) • Adherant Lactobacilli and Bifidobacteria significantly increase phagacytosis.
  48. 48. Hepatic encephalopathy – • By reducing level of ammonia in blood • synbiotic preparation-four probiotic strains and four fermentable fibers, including inulin and resistant starch reverse it in 30 days Obesity- • Fructans, daily consumption helps in reducing appetite. SCFA- stimulated secretion of gut peptides such as glucagon-like peptide (GLP)-1, peptide YY (PYY) and oxytomodulin and reduced secretion of ghrelin, all of which are secreted by endocrine-type cells in the mucosa. • lowering body weight or fat mass, and improving glucose tolerance Reduces the incidence and severity of sepsis in intensive care units
  49. 49. Challenges • Retention of viability of the probiotic bacteria • A serious problem of shelf instability had been encountered with dried Cultures. difficulty backing up label claims • Refrigerated products also have short lives due to negative effects of low temperature and formation of crystals on bacterial cells • Manufacturer must incorporate an excess of cells at the time the tablets are manufactured. This practice increases the cost and makes the use instructions inaccurate • Extreme temperatures, high pressure, shear forces can destroy the preperations • Survival of most bifidobacteria in most dairy products is poor due to low pH and/or exposure to oxygen • Difficulty in assessment of efficacy of pro and prebiotics M.S. Thantsha et al.Probiotics – What They Are, their Benefits and
  50. 50. Regulatory guidelines S.No Parameter Indian regulatory guidelines 1 Regulatory category of probiotics Drugs and functional foods 2 Regulatory authority for approval 1. Functional food are regulated by regulated by PFA (Prevention of Food Adulteration Act) as per The Food Safety and Standards Act (FSSA). 2. Drugs are regulated by FDA. 3 Recommended regulatory guidelines Guidelines are recommended for probiotics in food and major stress is on identification and evaluation of probiotic strain along with health claims and labeling claims. 4 Assessment of safety parameters FDA is responsible for the safety of drugs and food safety is responsibility of FSSA. ICMR guidelines can also be used to identify and evaluate safety.
  51. 51. 5 Requirements for approval Drugs: 1. Clinical data 2. Data to support study of products in humans: CMC, Stability, Pharmacology/ toxicology Functional foods: 1. Strain identification 2. Functional characterization 3. Safety assessment 4. Labeling requirement 6 Available probiotic products Sporolac, Yogurt, Darolac, Biglac, Bifilac etc. Biological products require pre-market review and approval by the FDA; however, dietary supplements do not Int. Jn of Biotechnology for Wellness Industries, 2013 Vol. 2, No. 2
  52. 52. Differences PREBIOTICS PROBIOTICS PREBIOTICS are a special form of dietary fiber PROBIOTICS are live bacteria in yogurt, dairy products and pills. There are hundreds of probiotic species available. Which of the hundreds of available probiotics is best is still unknown. PREBIOTIC powders are not affected by heat, cold, acid or time PROBIOTIC bacteria must be kept alive. They may be killed by heat, stomach acid or simply die with time Wide range of health benefits to the otherwise healthy person. Most of these have been medically proven PROBIOTICS are still not clearly known to provide health benefits to the otherwise healthy Nourish the good bacteria that everyone already has in their gut Must compete with the over 1000 bacteria species already in the gut May be helpful or preventative for irritable bowel (IBS), or inflammatory bowel disease (Crohn’s Disease,Ulcerative Colitis), colon polyps and cancer and those people with a leaky gut Certain PROBIOTIC species have been shown to be helpful for irritable bowel disease and for recurrence of certain bowel infections such as C. difficile
  53. 53. Prebiotic index • questions can be formulated as follows: • 1) Are the different prebiotics equally effective? • 2) Can a dose-effect relation be established? • To answer this, required thing is PI • Increase in the absolute number of bifidobacteria expressed(cfu per gm of feces) divided by the daily dose of prebiotic ingested(gms) • For inulin-type fructans, such a prebiotic index is of the order of a few (average . 4.00 ± 0.082) 108 cfu/g, Effects of Probiotics and Prebiotics
  54. 54. Symbiosis • Commensalism is a class of relationship between two organisms •  Mutualism: (facultative) both organisms benefit  Parasitism: (obligate) one organism benefits and the other one is harmed. Synbiotics • nutritional supplements combining probiotics and prebiotics in a form of synergism. term "synbiotic" be used only if the net health benefit is synergistic • Probiotics may colonise the upper intestine to avoid the adhering of pathogens to the intestinal tract and may help in digestion and prebiotic stimulate the microflora in the large intestine, combination thus works separately in the small and large intestine, but synergistically as they increase the overal gut health Eg: Bifidobacteria and fructo-oligosaccharides (FOS) Jn of Leukocyte Biology Volume 89, May 2011
  55. 55. Postbiotics  Probiotics provide benefit by way of metabolites such as enzymes, peptides, bacterions, and organic acids, called postbiotics. So culture supernatant of these bacteria mediates the immunomodulatory effect conferred to the host  They are important anions in the colonic lumen, affecting both Colonocyte Morphology (Proliferation / Differentiation) & Function (Tight Colonic Junction / Inflammatory Suppression).  Postbiotics biggest benefit? Nutrients, enzymes and peptides deliver an overall anti-inflammatory effect to slow or halt disease process in its tracks.  Use of postbiotic components as a safer alternative for clinical applications, especially in chronic inflammatory conditions like inflammatory bowel disease, where probiotics have not yet given encouraging results as far as induction of remission is concerned. Probiotics + prebiotics + postbiotics
  56. 56. The Probiotic Paradox • The Probiotic Paradox is that both live and dead bacteria in probiotic products can generate biological responses • Live probiotic cells influence both the gastrointestinal microflora and the immune response whilst the components of dead cells exert an anti-inflammatory response in the gastrointestinal tract • Difficult to assess the relative proportions of live and dead cells in a probiotic culture. • Contribute to the variation in response often seen with live probiotic cultures • Use of dead probiotics as biological response modifiers has several attractive advantages; such products would be very safe and have a long shelf-life.
  57. 57. Conclusion • Advocated by many health care professionals because of their evidence based health benefits in specific clinical scenarios • Prevention and alleviation of nonspecific and irregular complaints of the gastrointestinal tracts in healthy people • Prebiotics have great potential as agents to improve or maintain a balanced intestinal microflora to enhance health and wellbeing. • Still the rational usage, selection and design of probiotics remain important challenges for the scientific community in concern with their safety factors and an urgent need to address the quality, safety and efficacy issues of probiotics
  58. 58. References • Probiotics and prebiotics World Gastroenterology Organisation, 2008 • Probiotics – What They Are,Their Benefits and Challenges. New Advances in the Basic and Clinical Gastroenterology • Comparative Insight of Regulatory Guidelines for Probiotics in USA, India and Malaysia: A Critical Review. International Journal of Biotechnology for Wellness Industries, 2013, 2, 51- 64. • Prebiotics and Probiotics: A Critical Analysis by Vijay Prakash. Chap 57
  59. 59. Summary Microflora Mode of action Bifidobacteria species Reduced incidence of neonatal necrotizing enterocolitis Treatment of rotavirus diarrhea, balancing of intestinal microflora, treatment of viral diarrhea Enterococcus faecium Decreased duration of acute diarrhoea from gastroenteritis Lactobacillus strains pouchitis Lactose digestion improved, decreased diarrhoea and symptoms of intolerance in lactose intolerant individuals, children with diarrhoea, and individuals with short-bowel syndrome, as an adjunct to antibiotics Improved mucosal immune function, mucin secretion and prevention of disease Vaccine adjuvant, adherence to human intestinal cells, balancing of intestinal microflora
  60. 60. Saccharomyces boulardii Prevention of traveler’s diarrhea, prevention and treatment of C. difficile diarrhea, Shortened the duration of acute gastroenteritis Bacillus Sp Heat stable oral vaccine delivery, prophylactics and prevention of gastrointestinal infections Pediococcus Enhanced immune responses against infectious coccidioidal diseases