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

Neerja Hajela, Ph.D. General Manager - Science and Regulatory Affairs Yakult Danone India Pvt. Ltd.

Probiotics : What we Know and Where we are Going Next

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

Functional Food Market – Probiotics an important category

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 2nd Brain of the Human body- 100 million neurons and 2/3rd 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

O’Hara A.M. et al. EMBO reports 2006; 7: 688-693.

The intestinal microbiota – the forgotten organ

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?)

‘Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host’

Definition in 2001

Probiotic Guidelines - The Start

“ Guidelines for the Evaluation

• f

probiotics in Food. Report of a Joint FAO/WHO Working Group

• n

Drafting Guidelines for the Evaluation

• f 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.

“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.

Definition in 2014

Live cultures

Probiotic Not probiotic

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 Undefined consortia, including faecal microbiota transplant

Framework for Probiotic Products

Hill C et al (2014) Nat Rev Gastroenterol Hepatol 11:506–514.

Changing Perception

Low dose food supplement Old generation New generation

▪ Inactive ▪

• Eg. Yoghurts

▪ Not scientifically backed ▪ Doubtful efficacy ▪

• Eg. Yeast

▪ Scientifically tested ▪ Efficacy demonstrated ▪ Clear proof of concept

Inadequate amounts Health benefit not demonstrated WHO DEFINITION OF PROBIOTICS

“Live microorganisms which when administered in adequate amounts, confer a health benefit on the host.”

“FIT” “NO FIT”

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

• 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

Probiotic Characterization

• 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

• 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.

• 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

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

3758 children (1 to 5 years) Nutrient Group 1864 children Probiotic Group 1894 children

Probiotic drink (65 ml/ day）

 ❖ 

12week 12week Follow up



12week 12week

❖ 

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)

Double-blind Controlled Trial Determine & Compare incidence, duration, outcome, and pathogens of acute diarrhoea

7/12/07 10/13/07 1/5/08

Schematic Diagram

Variable Probiotic (n=1802) Nutrient (n=1783) Protective efficacy

• f probiotic (95%

CI)* Simple analysis# Percent Children with diarrhoea 608 674 Incidence of diarrhoea – no. of cases /child / year 0.88 1.029 14 (4-23) Occurrence of diarrhoea & protective efficacy of the probiotic

Benefit of the probiotic

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

• ptimal

expression

• f

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 Probiotics Along with Starter Yoghurt Curd Cheese Fermented with the probiotic

• nly

Fermented Milk Drinks

Ferment rmented ed Dairy ry Ma Matr trices ces for Probi biotic

• tics

Fermented Dairy Products

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

Probiotic Foods in Indian Market

Probiotic Strain Industrial processing as well as the food matrix

Influenced by

Small changes in properties may significantly alter in vivo functionality

➢ Adequate Quality Assurance and Good Manufacturing Practices - Safety and Efficacy ➢ CODEX General Principles

• f

Food Hygiene and Guidelines for application of Hazard Analysis and Critical Control Point (HACCP) should be followed.

Manufacturing Process

▪Safety ▪Stability ▪Survival ▪Efficacy

Probiotic Product

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).

(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.

Labelling for Probiotic Foods

 Cost savings from patients who do not acquire an infection

• r 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.

Why probiotics?

We are them e are them & The hey y ar are e us us