Dr SoumyaJunior Resident

Overview• Introduction• History• Concept of probiotics• MOA and examples of probiotics• Prebiotics and its examples• Clinical applications of pre/pro biotics• Synbiotics• Current status of probiotics in India• References

Intestine is a Paradise of disease

• Death sits in the bowels; a bad digestion is the root of all evil” - Hippocrates, 400 BC

History of Probiotics

• 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 conceptualize “Probiotics”

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 to indicate substances that were required for a healthy life

• Probiotics term coined in 1965 by Lilly And Stillwell.

• 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, Peyer’s patches and mesenteric lymph nodes)

• Our Intestine = 400 square meter surface…i.e. the surface area of a tennis court

Largest immune organ

• 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,Bifidobacterium and Acidophilus comprise the majority of healthy bacteria in the colon along with other disease producing bacteria.

Facts about Intestine

Factors affecting the intestinal micro ecosystem

• During infancy : Mother’s microbiology Mode of delivery Feeding practices

• Later in life :Antibiotics and other drug intakeMicrobial infectionsDiet (highly processed, low fiber)Chronic diarrheaStressChlorinated water

Gut Flora in Breast Fed vs Formula Fed

Babies

Dysbiosis is the abnormal microbial colonization of the intestine , where changes in Quantity and Quality of flora become Pathological & Harmful.

Common causes of dysbiosis:• Antibiotic therapy

• Autoimmune conditions , IBD

• Others are fast paced lifestyle, stress, food habits, Alcohol intake and cigarette smoking

Dysbiosis

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 :- GE foods, cereals supplemented with vitamins or minerals, genetically manipulated soybean and canola oil without trans-fatty acids

Nutraceuticals

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

Defining a probiotic

‘‘Live

microorganisms which when administered in adequate amounts confer a health benefit on the host’’

(WHO)

Why are Probiotics important for Human health?

Antibiotics

Alcohol consumption

Stress

Destroy the gut micro flora

Problems in digestion

Problems in absorption of

nutrients in the body

Emergence of antibiotic

resistant strains

Probiotics

Key properties of probiotic Non-pathogenic, non-toxic and non-allergic.

Capable of surviving and metabolizing in upper G.I. tract e.g. Resistant to low pH, organic acids, bile juice, saliva and gastric acid

Human in origin, genetically stable and capable of remaining viable for long periods in field condition.

Able to modulate immune response and provide resistance to disease through improved immunity or by the production of antimicrobial substance in the guts.

Contd….

Key properties of probiotic Good adhesion/ colonization to human intestinal tract

and influence on gut mucosal permeability.

Antagonistic against carcinogenic/ pathogenic organisms.

Clinically proven health benefit, e.g. gastrointestinal disorders, diarrhoea, clostridium difficle colitis, antibiotics associated diarrhoea, acute gastroenteritis.

Technologic properties for commercial viability such as stability of desired characteristics during processing, storage and transportation.

Bifidobacterium species

B. bifidum

B. longum

B. breve

B. infantis

B. lactis

B. adolescentis

Others

Bacillus cereus

Non pathogenic Escherichia coli

Saccharomyces cerevisiae (yeast)

Enterococcus faecalis

Streptococcus thermophilus

Examples of probioticsLactobacillus species

L. acidophilus

L. casei (rhamnosus)

L. reuteri

L. bulgaricus

L. plantarum

L. johnsonii

L. lactis

Mechanism of action Bioconversion of, for example, sugars into fermentation

products

Production of growth substrates, like vitamins B and K, for

other bacteria

Direct antagonism by antimicrobial substances:

– hydrogen peroxide– organic acids– Bacteriocin– acidophilin

Competitive exclusion for binding sites

Improved barrier function

Production of β- D- galactosidase

enzymes that break down lactose .

Reduction of inflammation, thus altering

intestinal properties

Stimulation of innate immune response

Mechanism of action

PROBIOTICS

NormaliseIntestine

ImmunomodulationMetabolic effects

Suppression of PPMs

Intestinal mucosal integrity

Regulation of bowel movement

IBS

Strengthens immunity

Alleviate food allergy symptoms

Control of IBD

Production of vitamins; improves digestion

Lactose tolerance

Lowers cholesterol(Bile acid deconjugation

& Secretion)

Foods containing Probiotics• Milk• Soya milk• Tofu• Milk products- Sour cream, Butter milk, Yoghurt• Fermented Indian foods like Idlis Dosas, uttapam Dhoklas Vadas Kadhi

Probiotic products marketed in India

India is an emerging market for probiotic products, being the largest producer of milk.

Amul , Mother dairy, Nestle Nesvita (first India’s Dahi with probiotics) and Yakult are the major brands.

Streptococcus faecalis T-110 30 millionClostridium butyricum TO-A 2 millionBacillus mesentericus TO-A 1 millionLactobacillus sporogenes 50 million

“PREBIOTICS”

PrebioticsThe concept of prebiotic was introduced by

Gibson & Roberfroid, in 1995

“Non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can improve host health."

Prebiotics- examplesGarlic, OnionsChicory rootAsparagusWheat Rye , Barleybreast milktomatoes, berriesbananas

Established prebioticsName 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 They represent the third largest component of Human Milk 20 - 23 gm/l in colostrum & 12- 14 gm/l in

mature milk

Clinical application of probiotics and prebiotics

Proven Benefits

• Diarrheal Illness - treatment and prevention

• Prevention of antibiotic-associated diarrhea (AAD)

• Treatment of Clostridium difficile infection

• Inflammatory bowel disease (ulcerative colitis,CD)

• Lactose intolerance

• Necrotizing Enterocolitis (NEC)

Suggested Benefits

• Food allergies

• Eczema

Holds Promise • Cystic fibrosis

• Dyslipidemia/

Cardiovascular

diseases

• Rheumatoid arthritis

• Traveller’s diarrhea /

bacterial enteritis

• Genitourinary tract

infections

• Allergic rhinitis

• Asthma

• Colic

• Colon cancer

prevention

• Obesity

• Hypertension

• In elderly

Clinical application of probiotics and prebiotics

Probiotics in the Treatment of Gastrointestinal Disorders

IBDUlcerative colitisCrohn’s diseasePouchitis

Constipation

Lactose Intolerance

H. pylori Eradication

DiarrheaAcute infectiousAntibiotic-associated C. difficile

Antibiotic associated diarrhea

(2006) 3, 606-607

Broad-spectrum antibiotics are associated with

the highest rate of AAD because of their

disruptive impact on the normal intestinal

flora.

Commonly implicated antibiotics – broad

spectrum penicillins (ampicillin),

Cephalosporins (Cefixime,cefalexin),

Clindamycin, Fluroquinolones.

Diarrhea is a common adverse effect of antibiotic

treatments.

Antibiotic associated diarrhea occurs in about 5-30% of

patients Probiotics used in prevention and as adjuvant therapy in AAD.

Disease Antibiotic treatment

Probiotics

Disturbance of

intestinal microbiota

Microbiota Clostridium overgrowth

in balance produces toxin

Antibiotic associated diarrhea

Lactose intolerance

Lactase digests lactose commonly present in milk and milk products.

Lactose is not digested when there is a deficiency in lactase and results in diarrhea.

Supplementation with probiotics has been shown to mitigate the symptoms of lactose intolerance by enzyme β- D- galactosidase.

Having yoghurt is a good way for a lactose intolerant person to get calcium.

Helicobacter pylori Infections

Chronic gastritis, Peptic ulcers, Gastric adenocarcinoma, and a number of non-gastrointestinal disorders.

Bifidobacteria and B. subtilis may inhibit the growth or attachment of H. pylori.

Possible mechanisms eradicates H. pylori include the ability of the probiotics to bind to gastric epithelial

cells, to produce a high quantity of lactic acid, and to proliferate rapidly.

Lactic acid bacilli

Increases production of Short chain Fatty Acid

Inhibits cholesterol syn by liver

Decreases blood chlesterol

Increases bile

.Bile syn. Increases

More cholesterol is used up

Decreases cholesterol

Hypercholesterolemia

Enzymes (Glycosidase, B- glucuronidase , azoreductase , and nitroreductase) of the intestinal flora convert the precarcinogens to active carcinogens giving rise to colon CA.

Probiotics reduce Faecal concentrations of enzymes Reduce absorption of harmful mutagens that may

contribute to colon carcinogenesis.

Activity of L. acidophilus and L. casei supplementation in humans helps to decrease levels of these enzymes

Probiotics and Cancer

Dosage of Probiotics

The dose of probiotics is usually expressed as the number of colony forming units (CFUs).

Due to the multitude of strains, the FDA has not approved any specific health claims for probiotics. The varying strains also make it impossible to establish an RDA for a probiotic.

Probiotic effects should be considered dose-specific

Dose listed on the label are based on studies that show a beneficial health effect in humans.

Prebiotics Probiotics

Prebiotics are defined as nonliving non-digestible special form of fiber or carbohydrates.

Probiotics are referred to as live active microorganisms that when administered in adequate amount will have beneficial effects to its

host.

The powder form of prebiotics can survive heat, cold, acid.

• more fragile.• vulnerable to heat. • may be killed over time.

Prebiotics perform their role by nourishing the bacteria that live in the intestines.

Probiotics fight the harmful bacterial species present in

the gut.

Prebiotics vs Probiotics

Adverse effects Probiotics side effects, if they occur, tend to be

mild and digestive symptoms. (such as gas or bloating).

May cause infections, especially in immuno- compromised patients.

Diabetic patients should be doubly cautious about taking probiotic drinks available in the market as they contain high level of sugar.

Probiotic products taken as a dietary supplement are manufactured and regulated as functional foods, not drugs.

Are probiotics supplements necessary?

Probiotics supplements are not necessary for normal, healthy individuals.

In healthy individuals, daily consumption of probiotics rich foods, particularly fermented dairy products like yoghurt adequately supplies the amount of probiotics required to maintain a healthy digestive system and overall wellbeing.

A diet high in starches and fibre provide prebiotics, which keep a healthy population of probiotics in our intestines.

Synbiotic = Probiotic + Prebiotic The concept of synbiotics has been

proposed to characterize health-

enhancing foods and supplements used

as functional food ingredients in humans

Potential synergy between pro- &

prebiotics

Improve survival in upper GIT

More efficient implantation

Eg: Bifidobacteria and fructo-oligosaccharides (FOS)

Synbiotics

Health benefits of Synbiotics

• Improved survival of live bacteria in food products, prolonged shelf life

• Increased number of ingested bacteria reaching the colon in a viable form

• Stimulation in the colon of the growth and implantation of both exogenous and endogenous bacteria

• Activation of metabolism of beneficial bacteria, antagonistic toward pathogenic bacteria

Probiotic market

Increased from $14.9 billion in 2007 to an estimated $15.9 billion by the end of 2008. It is expected to reach $36.7 billion by 2018, a compound annual growth rate (CAGR) of 6.2%.

Japan accounted for the largest share of total sales in 2007 with 39.5%, driven primarily by the country’s large and well-developed probiotic foods segment.

Source: http://www.bccresearch.com/market-research/food-and-beverage/probiotics-market-fod035d.html

Status of Probiotics in India

• Indian probiotic industry is in its infancy stage and presently accounts for only a small fraction i.e. less than 1% of the total world market turnover in the probiotic industry.

• Apart from human use, also used as animal feed supplements for cattle, poultry and piggery.

• The latest and recent addition to the list of probiotics in India is ViBact (which is made up of genetically modified Bacillus mesentricus), which acts as an alternate to B-complex.

Institutes engaged in Probiotic research in India

Central Food Technology And Research Institute, Mysore, India

National dairy research institute, Karnal, Haryana, India

• Institute of microbial technology, Chandigarh, India

• National dairy development board, Anand, Gujarat, India

Nestle Pvt Ltd, Panipat, Haryana, India

Human Microbiome ProjectThe Human Microbiome Project (HMP)

2008, aims to characterize the microbial communities found at several different sites in the human body, including nasal passages, oral cavities, skin, GI tract, and urogenital tract, and to analyze the role of these microbes in human health and disease.