Probiotics : What we Know and Where we are Going Next Neerja Hajela, Ph.D. General Manager - Science and Regulatory Affairs Yakult Danone India Pvt. Ltd.
Functional Food Market Probiotics an important category Global functional foods market revenue by product, 2015 & 2024 (USD Billion) Functional Foods Market Analysis By Product (Carotenoids, Dietary Fibers, Fatty Acids, Minerals, Prebiotics & Probiotics, Vitamins), By Application, By End-Use (Sports Nutrition, Weight Management, Immunity, Digestive Health) And Segment Forecasts, 2014 To 2024: Market research Report
Expected Probiotic Market Growth (2013-2022) Asia-pacific ranks as the fastest growing market, Japan, Europe and the United States represents major market worldwide. Industry participants majorly include Chr. Hansen Holding A/S, Yakult Honsha Co., Ltd., Danone, Nestle, Probi AB, Danisco A/S, Lallemand Inc., and Arla Foods, Inc. Probiotics Market Analysis and Reports UK Conference Series 2017
Intestinal Health the reason for Probiotics
The Intestine what we did not know.. Digestion of food and absorption of nutrients 2 nd Brain of the Human body- 100 million neurons and 2/3 rd of the body s neurotransmitters Largest immune organ 70 % of the immune cells are present here 100 trillion microbes outnumber the human cells by a factor of 10 intestinal microbiota
The intestinal microbiota the forgotten organ O Hara A.M. et al. EMBO reports 2006; 7: 688-693.
Dysbiosis of the intestinal microbiota link to disease?
Microbes in the Gut
Gut Dysbiosis
Interventions for modulation of the intestinal microbiota
Favorable modification of the gut flora Probiotics Live microorganisms which when administered in adequate amounts confer a health benefit on the host. FAO/WHO (2001) Prebiotics Prebiotics are non-digestible substances that when consumed provide a beneficial physiological effect on the host by selectively stimulating the favourable growth or activity of a limited number of indigenous bacteria. Gibson GR & Roberfroid MB (1995) Synbiotics Probiotic + prebiotic (synergy?)
Definition in 2001 Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host
Probiotic Guidelines - The Start Guidelines for the Evaluation of probiotics in Food. Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of probiotics in Food. London Ontario, Canada. April 30 and May 1, 2002. Joint Food and Agriculture Organization/World Health Organization: Guidelines for the evaluation of probiotics in foods. London, Ontario, Canada; 2002, 1-11.
Definition in 2014 live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Hill C et al (2014) Nat Rev Gastroenterol Hepatol 11:506 514.
Framework for Probiotic Products Probiotic Live cultures Probiotic drugs Probiotic medical foods Probiotic foods Non-oral probiotics Probiotic animal feed Defined microbial consortia Probiotic dietary supplement Probiotic infant formula Fermented foods with undefined microbial content Not probiotic Undefined consortia, including faecal microbiota transplant Hill C et al (2014) Nat Rev Gastroenterol Hepatol 11:506 514.
Changing Perception Low dose food supplement Inactive Eg. Yoghurts Old generation Not scientifically backed Doubtful efficacy Eg. Yeast NO FIT New generation Scientifically tested Efficacy demonstrated Clear proof of concept FIT WHO DEFINITION OF PROBIOTICS Inadequate amounts Health benefit not demonstrated Live microorganisms which when administered in adequate amounts, confer a health benefit on the host.
Probiotic - Characterization and Benefits
What makes a Probiotic? Stable and well-described organism, Nontoxic, Non-pathogenic, Generally Recognized As Safe (GRAS) Resistant to Gastric juices, Bile and Pancreatic juices Able to transit the Gastro-intestinal Tract and transiently colonize the target site small intestine/ large intestine Impart a scientifically proven health benefit.
Probiotic Organisms
Probiotic Characterization 1. Genus, Species and Strain identification - Phenotypic and Genotypic tests validated standard methodology 2. In vitro tests to screen potential probiotic strains - Resistance to gastric acid, bile and pancreatic juice - Antimicrobial activity - Bile salt hydrolase activity - Ability to reduce pathogen adhesion 3. In vivo safety studies in animals - Subsequent testing in animal (rats and mice) models Assessment of acute, sub acute and chronic toxicity - Not necessary for strains with documented established use
4. In vivo efficacy studies in animals Validated animal models to be used prior to human trials 5. Evaluation of safety of the probiotic for human use - Generally Recognized as Safe - Antibiotic Resistance patterns - Toxin production or hemolytic activity - Immune compromised individuals 6. Evaluation of efficacy in humans Clinically significant improvement in condition, reduced risk of disease, or longer time to next occurrence, faster recovery from illness. 7. Probiotic benefits - Acute Gastroenteritis, Irritable Bowel Syndrome, Necrotizing Enterocolitis. - Probiotic benefits in other aspects of health functionality obesity and metabolic disorders, prevention of cancers, cognitive and mood enhancing benefits.
Study - Meta analysis; 84 trials ; n - 10351 patients Eight different Gastrointestinal disorders Infectious diarrhoea, Pouchitis, AAD, Traveler's diarrhoea, IBS, C diff infection, NEC. Conclusion: Probiotics are generally beneficial in treatment and prevention of gastrointestinal diseases.
Study : Cochrane review, 63 studies, n- 8014 subjects Conclusion: Probiotics appear to be safe and shortened duration of diarrhoea and reduced stool frequency in acute infectious diarrhoea. Allen SJ et al (2010) Cochrane Database of Systematic Reviews 11:CD003048.
An Indian study
Schematic Diagram Probiotic Group 1894 children 7/12/07 10/13/07 1/5/08 Probiotic drink (65 ml/ day) Follow up 12week 12week 3758 children (1 to 5 years) Double-blind Controlled Trial Nutrient Group 1864 children Determine & Compare incidence, duration, outcome, and pathogens of acute diarrhoea 12week 12week Nutrient (65 ml/ day) Follow up Nutritional assessment (height, weight and mid-arm circumference) will be done at the, and (beginning, after 12weeks, and at the end of follow-up)
Benefit of the probiotic Occurrence of diarrhoea & protective efficacy of the probiotic Variable Children with diarrhoea Incidence of diarrhoea no. of cases /child / year Probiotic (n=1802) 608 674 Nutrient (n=1783) Protective efficacy of probiotic (95% CI)* Simple analysis # Percent 0.88 1.029 14 (4-23) Probiotic - Protective efficacy 14% (95% CI: 4%,23%)
Recommendations European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Probiotics in the management of acute gastroenteritis in children Probiotics for children with mild Ulcerative Colitis when standard therapy isn t working. European Society of Primary Care Medicine Probiotics in management of lower gastrointestinal symptoms in clinical practice. World Gastroenterology Organization Probiotics for different gastrointestinal indications - for adults and children. World Allergy Organization Likely benefit from probiotic use in pregnant women who are at risk of having an allergic child or in infants at high risk of developing allergy.
Quantities Probiotic benefits are strain specific No general minimal level for the probiotic count Bifidobacterium infantis 35624 was effective in alleviating symptoms of IBS at 100 million cfu/ day, whereas studies with VSL#3 have used sachets with 300 450 billion cfu/day.
Carrier matrix and probiotic products
Dairy The Preferred Medium Low ph of the product Buffers stomach acidity - ensures viability of the probiotic bacteria. Short shelf life or refrigeration - Probiotic survival in product. Nutrition and optimal expression of probiotic functionality Compliance - Food vs. Pill. Dairy based probiotic foods represent the largest segment accounting for nearly 65% of the total probiotic food market.
Fermented Dairy Matrices for Probiotics Fermented Dairy Products Fermented Dairy Probiotics Along with Starter Fermented with the probiotic only Yoghurt Curd Cheese Fermented Milk Drinks
Probiotic Foods in Indian Market Lactobacillus acidophillus and Bifidobacterium lactis Lactobacillus acidophilus Lactobacillus casei strain Shirota LA5 Bifidobacterium bifidus, Streptococcus thermophillus, Lactobacillus bulgaricus and Lactobacillus acidophillus strains ( Min 10 7 Bacteria /ml. BB 12
Manufacturing Process Probiotic Strain Influenced by Industrial processing as well as the food matrix Small changes in properties may significantly alter in vivo functionality Adequate Quality Assurance and Good Manufacturing Practices - Safety and Efficacy CODEX General Principles of Food Hygiene and Guidelines for application of Hazard Analysis and Critical Control Point (HACCP) should be followed.
Probiotic Product Safety Stability Survival Efficacy
Probiotic Guidelines and Regulations
Probiotic categorization across the Globe
Guidelines for evaluation of candidate probiotic strains Strain Identification by Phenotypic and Genotypic Methods Genus, Species and Strain Deposit strain in an Internationally Recognized collection Screening of Potential Probiotic Strains In vitro Tests In vivo studies in validated animal models for : Safety Efficacy In vivo studies in humans for clinical evaluations Phase 1 (Safety) Phase 2 (Efficacy) Phase 3 (Effectiveness)* PROBIOTIC FOODS Labeling Requirements Genus, Species, Strain Minimum viable numbers of Probiotics at the level at which efficacy is claimed and at the end of shelf-life Health claim (s) Serving size for efficacy Storage conditions
MINISTRY OF HEALTH AND FAMILY WELFARE (FOOD SAFETY AND STANDARDS AUTHORITY OF INDIA) NOTIFICATION New Delhi, the 23rd December, 2016 Gazette Notification of Food Safety and Standards (Food or Health Supplements, Nutraceuticals, Foods for Special Dietary Uses, Foods for Special Medical Purpose, Functional Foods and Novel Food) Regulations, 2016 (Uploaded on: 06.01.2017).
Labelling for Probiotic Foods (iii) Every package of probiotic food shall carry the following information on the label, namely:- a) the words PROBIOTIC FOOD ; b) Genus and species including strain designation or culture collection number, where applicable, in brackets where probiotics are mentioned in the list of ingredients; c) Viable numbers at the end of the shelf-life of probiotic strain corresponding to the level at which the efficacy is claimed; d) the recommended serving size which shall deliver the effective viable dose of probiotics related to health claims and recommended duration of use, proper storage temperature conditions, and time limit for Best Use after opening the container; e) an advisory warning NOT FOR MEDICINAL USE prominently written; and f) a warning or any other precaution to be taken while consuming, known side effects, if any, contraindications, and product-drug interactions, as applicable.
Why probiotics? Cost savings from patients who do not acquire an infection or recover more quickly driving forces in making probiotics a part of the health care system. Use of probiotics to prevent and treat respiratory tract infections saving of $100 million /year (Canada and France). We live in a microbial world its time to design how we live around the microbes rather than only respond when the wrong ones attack us.
We are them & They are us