Probiotics, Prebiotics and

synbiotics Dr. Louay Labban

A’Sahrqiyah University

Definition

• We usually think of bacteria as something that causes diseases. But the body is full of bacteria, both good and bad. Probiotics are often called "good" or "helpful" bacteria because they help keep your gut healthy.

Definition

• Probiotics are live bacteria and yeasts that are good for and have beneficial effects on the host by improving its intestinal microbial balance.

HISTORY

• At the start of the 20th century, Russian noble prize winner and father of modern immunology, Elie Metchnikoff, a scientist at the Pasteur institute, was the first conceptualize “probiotics”.

Elie Metchnikoff

• In 1907 Metchniokoff proposed that the acid producing bacteria in fermented milk products could prevent “fouling” in the large intestine and if consumed regularly, lead to a longer, healthier life

Initial Intentional Probiotic Use

• Eli Metchnikoff observed–Bulgarians who drank milk fermented by

lactic-acid producing bacteria had long lives– Lactic acid lowers gut pH and inhibits the

growth of some pathogenic bacteria.

• Metchnikoff began drinking fermented milk and soon Parisian physicians did likewise.

• Henry Tissier at Pasteur Institute identified bacteria common in breastfed infant stool: Bifidobacter

• Lactobacillus acidophilus breaks down lactose and allows lactose intolerant individuals to drink milk

• In early 1930’s, in Japan, Minoru shirota developed a fermented milk product called Yakult (probiotic yogurt like product made by fermenting a mixture of skimmed milk with a special strain of Lactobacillus casei shirota).

• Probiotic term coined in 1965 by Lilly and Stillwell.

Newborn Microbiota

Initially depends on• Mother’s microbiota maternal vaginal and

intestinal flora constitutes the source of bacteria, which colonizes the intestine of new born.

• Mode of deliver • Birth environment

• Rarely genetic factors• After infantry probiotics supplied from raw

foods; such as lactic acid fermented foods such as yogurt, cheese and probiotic supplements.

Factors affecting the intestinal micro ecosystem

• Antibiotics and other drug intake• Microbial infections• Diet (highly processed, low fiber foods)• Chronic diarrhea• Stress• Chlorinated water• Radiation and chemotherapy• Colonic therapies for detoxification

Characteristics of Effective Probiotics

• Able to survive the passage through the digestive system.

• Able to attach to the intestinal epithelia and colonize.

• Able to maintain good viability.• Able to utilize the nutrients and substrates in a

normal diet.

• non pathogenic and non toxic.• Capable of exerting a beneficial effect on the

host.• Stability of desired characteristics during

processing, storage and transportation.• Anti-inflammatory, antimutagenic,

immunostimulatory.

Benefits of probiotics

Advantages

• Produce lactic acid- lowers the pH of intestines and inhibiting bacterial villains such as Clostridium, Salmonella, Shigella, E. coli.

• Decreases the production of a variety of toxic or carcinogenic metabolites.

• Aid absorption of minerals, especially calcium, due to increased intestinal acidity.

• Production of β- D- galactosidase enzymes that break down lactose.

• Produce a wide range of antimicrobial substances -acidophilin and bacteriocin etc. help to control pathogenic bacteria .

• Produce vitamins ( Vitamin B and vitamin K)• Act as barriers to prevent harmful bacteria

from colonizing the intestines

• Colon cancer – Certain probiotics (Lactobacillus bulcaricus) may help prevent colon cancer by preventing the

• Breakdown of enzymes (β- glucuronidase) that contribute to the growth of cancer causing agents.

• Lowering cholesterol : break down bile in the gut, thus inhibiting its reabsorption (which enters the blood as cholesterol)

• Blood pressure reduction - Consumption of milk fermented may result in modest reductions in blood pressure, due to the ACE inhibition-like peptides produced during fermentation.

Antibiotic associated diarrhea(AAD)

• 1. Results from an imbalance in the colonic microbiota

• 2.Probiotic treatment can reduce the incidence and severity of AAD

• 3.Efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.

Allergy

• Degradation/structural modification of enteral antigens.

• Normalization of the properties of aberrant indigenous microbiota and of gut barrier functions.

• Regulation of the secretion of inflammatory mediators, and promoting development of the immune system.

• Prevents food allergy by promoting endogenous barrier mechanisms and alleviating intestinal inflammation.

• Stimulating immune response and reduction of serum IgE levels.

• Reduction of Th2 cytokine response.

Primary Pediatric Uses of Probiotics

• Manage lactose intolerance (L acidophilus)• Antibiotic-associated diarrhea and

infectious diarrhea• Decrease constipation• Decrease dental caries• Treatment of H pylorii infections• Decrease colic• Decrease risk of developing eczema• Decrease upper respiratory tract infections

Probiotic strains

• Lactobacillus species• L. acidophilus• L. plantarum• L. casei subspecies rhamnosus• L. brevis• L. delbreuckii subspecies bulgaricus

Bifidobacterium species • B. adolescentis• B. bifidum• B. longum • B. infantis• B. breve

Others

• Streptococcus salivarius ssp. thermophilus• Lactococcus lactis ssp. lactis• Lactococcus lactis s ssp. cremoris• Enterococcus faecium• Leuconostoc mesenteroides ssp. dextranicum• Propionibacterium freudenreichii• Pediococcus acidilactici• Saccharomyces boulardii

Intestinal Microflora: Location & Prevalence

• Rare in the esophagus• Uncommon in the stomach• primarily gram (+)• in the jejunum – primarily aerobes• in the colon • primarily anerobes• more anerobes than aerobes

Probiotics: proposed mechanisms

• Adherence and subsequent stimulation of gut immune system–Up-regulation of mucin gene– Enhance secretory IgA–Maintain normal macrophage function

• Competition for essential nutrients• Production of antimicrobial factors• Provide favorable environment for growth of

other beneficial bacteria• Production of short-chain fatty acids with anti-

inflammatory properties

Probiotic Consumption

• Minimum Consumption: 100g of a probiotic food with 107 colony f forming unit (CFU)/ g.

• most probiotics do not permanently adhere in the intestine, but exert their effects as they metabolize and grow during their passage through the intestine (colonization). Thus, daily consumption of these bacteria is probably the best way to maintain their effectiveness

Dosage Forms

Standard forms:• Capsules• Sticks• Powder blends• Chewable tablets• Sachets

Probiotic foods

• Some fermented products containing similar lactic acid bacteria include:

• Pickled vegetables• Fermented bean paste such as tempeh,• Miso and doenjang• Kefir

• Buttermilk or Karnemelk• Kimchi • Pao cai• Sauerkraut• Soy sauce• Zha cai

Pickled vegetables

Kimche and zha cai

Kefir

Sauerkraut

Probiotic Foods

• Yogurt• Usually made from milk (rarely, from cream) inoculated

with Streptococcus thermophilus and either Lactobacillus acidophilus or Lactobacillus bulgaricus.

• Turkish in origin• Available in innumerable forms and flavors• 1. Lowfat chocolate yogurt• 2. Drinkable fruit-flavored goat yogurt• 3. Neon-colored yogurt in squeeze tubes

Frozen Yogurt

• LaLoo’s Goat’s Milk Frozen Yogurt, naturally chock-full of S. Thermophilus, L. Bulgaricus, L. Acidophilus and Bifidus.Juice

First probiotic juice launched in the fall of 2007 by Next Foods.Goodbelly, organic fruit juice-based probiotic beverage , contains L.Plantarum 299v, has effects on irritable bowel syndromeThree initial flavors include Brilliant Blueberry, Peach Mango and Strawberry Rosehip

• Attune Foods:Chocolate & Granola barsAttune makes Wellness Bars in three chocolate varieties and three yogurt and granola varieties.All products contain “more than 5 times the live active cultures in yogurt, with less sugar.Kashi Vive Probiotic DigestiveWellness Cereal Vive contains one billion CFUs of Lactobacillus acidophilus per serving.

• Yakult Dairy Drink• Probiotic, cultured dairy beverage• Has citrus flavor • Sold in single-shot • containers that contain around • 8 billion live and active Lactobacillus • casei Shirota cells per bottle

• Ricera Rice Yogurt• An organic, non-dairy, rice “yogurt” with

whole grains and live, active cultures, including Lactobacillus bulgaricus, Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacterium bifidum.

Effect of factors on Survival of probiotics in FOOD

• physiological state of the added probiotic in the food

• physicochemical conditions of food processing

• physical conditions of product storage, like temperature

• chemical composition of the product, such as content of nutrients, oxygen (Bifidobacterium) or pH

• interactions with other product components, that can be inhibitory or protective

Side Effects of Probiotics

• Rare cases cause bloating, diarrhea, abdominal pain.

• If in excess cause infection that require medical attentions.

• People having on underlying disease or compromised immune system cause potential health problems like skin rash, fever, bloody stools etc.

• Sometimes interact with immunosupressive drugs leading to life threating conditions. So people taking such drugs should avoid it.

What is a prebiotic?

• 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, and thus improve host health”

• First identified in 1995

• Typically oligosaccharides: galactooligosaccharides (GOS), fructo-OS (FOS), xylo-OS (XOS), Inulin

• Found in: Breastmilk, Jerusalem artichoke, chicory root, raw dandelion greens, leeks, onions, garlic, asparagus, whole grains, beans, banana

• Adding Prebiotics to Probiotics increases production of gut Short-Chain Fatty Acids (SCFA)

• It should increase the number and/or activity of bifidobacteria and lactic acid bacteria

Prebiotics

• Traditional dietary sources of prebiotics include soybeans, inulin sources (such as Jerusalem artichoke, jicama, and chicory root), raw oats, unrefined wheat, and unrefined barley .

• Some of the oligosaccharides that naturally occur in breast milk are believed to play an important role in the development of a healthy immune system in infants, but these are not considered prebiotics, as they do not act through the intestinal microflora.

Prebiotics

• A prebiotic is a nondigestible component which beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of colonic bacteria, thereby improving the health of the host .

• Examples- insulin, garlic, onions, chicory root, Asparagus, whole wheat, rye, barley

Characteristics of Prebiotics

• Should not be hydrolyzed or absorbed in the upper part of G.I tract.

• Should be a selective substrate for one or a limited number of potentially bacterial commercial to the colon culture protagonist.

• Should be able to alter the colonic microflora towards a healthier composition or selectively stimulates the growth and or activity of intestinal bacteria associated with health and well being.

• Should help increase the absorption of certain minerals such as calcium and magnesium.

• Favorable effect on the immune system and provide improved resistance against infection.

• Prebiotics are a category of nutritional compounds grouped together by the ability to promote the growth of specific beneficial (probiotic) gut bacteria. Inulin-type prebiotics contain fructans of the inulin-type.

• Fructans are a category of nutritional compounds that encompasses naturally occurring plant oligo- and polysaccharides in which one or more fructosyl-fructose linkages comprise the majority of glycosidic bonds.

• To be “inulin-type” a fructan must resist enzymatic hydrolysis by human salivary and small intestinal digestive enzymes.

• Inulin-type prebiotics include:• Fructooligosaccharides (FOS)• Oligofructose• Inulin

• Some inulin-type prebiotics are relatively high in free sugars (the monosaccharides fructose and glucose and the disaccharide sucrose), while others have most or all free sugars removed.

• Processing can also result in mixes consisting exclusively of inulin-type oligosaccharides, polysaccharides, or both. Because inulin, oligofructose, and FOS resist enzymatic digestion in the upper gastrointestinal tract, they reach the Colon virtually intact where they undergo bacterial fermentation.

• . All inulin-type prebiotics are bifidogenic – stimulating the growth of Bifidobacteria species. The effects they have on other gut organisms are less consistent.

• A minimal dose of inulin-type prebiotic appears to be needed to produce a bifidogenic effect. However, intraindividual response to an identical dose of the same inulin-type prebiotic, in terms of stimulation of total number of Bifidobacteria and individual Bifidobacteria species, can be variable.

• Thus, the desirable bacteria (bifidobacteria and lactobacilli) become more prominent in the gut, and this is beneficial for the human host. In addition, some of the fermentation end-products such as short chain fatty acids (SCFAs) help to promote human health.

• Therefore a prebiotic should fulfil three criteria: 1- Resists gastric acidity, hydrolysis by mammalian

enzymes and gastrointestinal absorption.2- Is fermented by the intestinal microflora.3- Stimulates selectively the growth and/or activity

of intestinal bacteria associated with health and• wellbeing.

• This concept implies that prebiotics must be stable in the stomach, i.e. that acid would not influence them, and they should not be absorbed in the small intestine and thus able to reach the colon, where they are selectively fermented by specific bacteria which exert the beneficial effect on the host .

What Is scFOS?

• Fructans have been defined as “any compound where one or more fructosyl– fructose linkages constitutes a majority of linkages …

• Fructans can vary with respect to the following :

• Sources: • Plant• Bacteria• Fungi •

Synbiotics

• PROBIOTICS + PREBIOTICS• Foods containing the combination of

probiotics and prebiotics are referred to as sybiotics.

• Improved survival in upper GIT and more efficient implantation.

Take home points…• Good evidence for:– Infectious diarrhea, tx– Antibx-assoc diarrhea– NEC; premature

mortality• Promising evidence for:– Preventiong atopic

conditions– Constipation

• In the future we may be using probiotics as we use antibiotics today: with specific strains used for certain clinical situations guided by controlled studies

• Prescribing– Lactobacillus GG

best studied to date– Combination

products not well studied, but may work as well

– 10 billion organisms/d

– Keep refrigerated (except Culturelle and BioGaia)

– Give in cool food/drink

– 2% risk bloating/gas