Probiotics : What we Know and Where we are Going Next Neerja - PowerPoint PPT Presentation

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 Live cultures Probiotic Probiotic drugs Not Probiotic medical foods probiotic Probiotic foods Non-oral probiotics Fermented Undefined Probiotic animal feed foods with consortia, undefined including Defined microbial consortia microbial faecal Probiotic dietary supplement content microbiota transplant Probiotic infant formula Hill C et al (2014) Nat Rev Gastroenterol Hepatol 11:506 – 514.

Changing Perception Low dose food Old New supplement generation generation ▪ Not scientifically ▪ Scientifically Inactive ▪ backed tested Eg. Yoghurts ▪ Doubtful efficacy Efficacy ▪ ▪ ▪ Eg. Yeast demonstrated “FIT” ▪ Clear proof of concept “NO FIT” WHO DEFINITION OF PROBIOTICS “Live microorganisms Inadequate Health benefit which when administered amounts not in adequate amounts, confer a health benefit on demonstrated the host. ”

Probiotic - Characterization and Benefits

What makes a Probiotic ? ▪ Stable and well-described organism, Non- toxic, 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 7/12/07 10/13/07 1/5/08 Probiotic drink Follow up (65 ml/ day ） Probiotic Group 1894 children 12week 12week  ❖  Double-blind 3758 children Determine & Compare incidence, Controlled Trial (1 to 5 years) duration, outcome, and pathogens of acute diarrhoea 12week 12week  ❖  Nutrient Group 1864 children Follow up Nutrient (65 ml/ day) ➢ 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 Probiotic Nutrient Protective efficacy of probiotic (95% (n=1802) (n=1783) CI)* Simple analysis # Percent Children with 608 674 diarrhoea Incidence of diarrhoea 0.88 1.029 14 (4-23) – no. of cases /child / year 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.

Ferment rmented ed Dairy ry Ma Matr trices ces for Probi biotic otics Fermented Dairy Products Fermented Dairy Probiotics Fermented with the probiotic Along with Starter only Yoghurt Curd Cheese Fermented Milk Drinks

Probiotic Foods in Indian Market Lactobacillus Lactobacillus acidophillus acidophilus and Bifidobacterium lactis Lactobacillus casei strain Shirota Bifidobacterium bifidus, Streptococcus thermophillus, Lactobacillus bulgaricus and LA5 Lactobacillus acidophillus strains BB 12 ( Min 10 7 Bacteria /ml.