A Project Report on PROBIOTICS

Project work submitted for partial fulfillment for the award of bachelor of pharmacy (B.Pharma.) degree.

Supervised By: Mr.Sandeep Kataria Assit.Professor

Submitted By: Shyam Sunder Jayalwal B.Pharma.Final year

MAHARSHI ARVIND INSTITUTE OF PHARMACY, JAIPUR 2011-2012

Certificate

This is certify that Mr. Shyam Sunder Jayalwal student of B.Pharma. IV year (Session 2011-2012) has carried out the project work entitled Probiotics as a literature survey during final year for the partial fulfillment for the award of Bachelor of Pharmacy degree, under direct supervision of me.

Mr. Sandeep Kataria Assistant Professor MAIP, Jaipur

Dr. RAJESH ASIJA Principal MAIP, Jaipur

ACKNOWLEDGEMENT
My efforts this project reports were supported by many people, directly or indirectly, and I would like to take this opportunity to thank them all them for their assistance. I consider myself most lucky to work under the able guidance of Mr. Sandeep Kataria. I take this opportunity to express my heartfelt gratitude to my reverend guide, his discipline, principle, simplicity caring attitude and provision of fearless work environment will be cherished in all walk of my life. I am very much grateful to him for his invaluable guidance and everlasting encouragement throughout my course. I am immensely thankful Dr. RAJESH ASIJA(PRINCIPAL) Maharishi Arvind Institute Of Pharmacy, Jaipur for providing me the necessary facilities and help in carrying out my project work. I owe my warmest and humble thanks to pharmacy faculty, Teaching staff of Maharishi Arvind Institute Of Pharmacy, Jaipur for their timely help encouragement, boosting my confidence in the progress of my academics. I express my deepest and special thanks to my batch mates for their kind cooperation, and encouragement through my graduation. Last but not the least I thank GOD the almighty father, mother for their blessing and courage to ladder the success. Thankful I ever remain..

SHYAM SUNDER JAYALWAL (B.PHARMA, FINAL YEAR)

TABLE OF CONTENTS

S.NO. Chapter
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INTRODUCTION PRELIMINARY RESEARCH AND POTENTIAL EFFECTS FACTORS AFFECTING VIABILITY IN FOODS TYPES OF PROBIOTICS HEALTH BENEFITS OF PROBIOTICS WHAT FOODS CONTAIN PROBIOTICS? HOW SHOULD PEOPLE TAKE PROBIOTICS? THE SIDE EFFECTS AND RISKS OF PROBIOTICS EFSA OPINIONS OF PROBIOTICS REFERENCES

Page No.
1-4 5-9 10-14 15-21 22 23 24 25-26 27 28-30

Chapter-1

INTRODUCTION

Chapter-1

Introduction

INTRODUCTION:
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host".[1] Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be used. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements.

Etymologically, the term appears to be a composite of the Latin preposition pro ("for") and the Greek adjective (biotic), the latter deriving from the noun (bios, "life").[2] At the start of the 20th century, probiotics were thought to beneficially affect the host by improving its intestinal microbial balance, thus inhibiting pathogens and toxin producing bacteria. Today, specific health effects are being investigated and documented including alleviation of chronic intestinal inflammatory diseases, prevention and treatment of pathogen-induced diarrhea, urogenital infections, and atopic diseases.[3] To date, the European Food Safety Authority has rejected most claims that are made about probiotic products, saying they are unproven. [4]

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-1

Introduction

Histry:

lie Metchnikoff The original observation of the positive role played by certain bacteria was first introduced by Russian scientist and Nobel laureate lie Metchnikoff, who in the beginning of the 20th century suggested that it would be possible to modify the gut flora and to replace harmful microbes with useful microbes.[3] Metchnikoff, at that time a professor at the Pasteur Institute in Paris, proposed the hypothesis that the aging process results from the activity of putrefactive (proteolytic) microbes producing toxic substances in the large bowel. Proteolytic bacteria such as clostridia, which are part of the normal gut flora, produce toxic substances including phenols, indols and ammonia from the digestion of proteins. According to Metchnikoff these compounds were responsible for what he called "intestinal auto-intoxication", which caused the physical changes associated with old age. It was at that time known that milk fermented with lactic-acid bacteria inhibits the growth of proteolytic bacteria because of the low pH produced by the fermentation of lactose. Metchnikoff had also observed that certain rural populations in Europe, for example in Bulgaria and the Russian steppes who lived largely on milk fermented by lactic-acid bacteria were exceptionally long lived. Based on these facts, Metchnikoff proposed that consumption of fermented milk would "seed" the intestine with harmless lactic-acid bacteria and decrease the intestinal pH and that this would suppress the growth of proteolytic bacteria. Metchnikoff himself introduced in his Maharishi Arvind Institute of Pharmacy, Jaipur 2

Chapter-1

Introduction

diet sour milk fermented with the bacteria he called "Bulgarian Bacillus" and found his health benefited. Friends in Paris soon followed his example and physicians began prescribing the sour milk diet for their patients. Bifidobacteria were first isolated from a breast-fed infant by Henry Tissier who also worked at the Pasteur Institute. The isolated bacterium named Bacillus bifidus communis was later renamed to the genus Bifidobacterium. Tissier found that bifidobacteria are dominant in the gut flora of breast-fed babies and he observed clinical benefits from treating diarrhea in infants with bifidobacteria. The claimed effect was bifidobacterial displacement of proteolytic bacteria causing the disease. During an outbreak of shigellosis in 1917, German professor Alfred Nissle isolated a strain of Escherichia coli from the feces of a soldier who was not affected by the disease. Methods of treating infectious diseases were needed at that time when antibiotics were not yet available, and Nissle used the Escherichia coli Nissle 1917 strain in acute gastrointestinal infectious salmonellosis and shigellosis. In 1920, Rettger demonstrated that Metchnikoff's "Bulgarian Bacillus", later called Lactobacillus delbrueckii subsp. bulgaricus, could not live in the human intestine, and the fermented food phenomenon petered out. Metchnikoff's theory was disputable (at this stage), and people doubted his theory of longevity. After Metchnikoff's death in 1916, the centre of activity moved to the United States. It was reasoned that bacteria originating from the gut were more likely to produce the desired effect in the gut, and in 1935 certain strains of Lactobacillus acidophilus were found to be very active when implanted in the human digestive tract. Trials were carried out using this organism, and encouraging results were obtained especially in the relief of chronic constipation. The term "probiotics" was first introduced in 1953 by Werner Kollath. Contrasting antibiotics, probiotics were defined as microbially derived factors that stimulate the growth of other microorganisms. In 1989, Roy Fuller suggested a definition of probiotics that has been widely used: "A live microbial feed supplement which Maharishi Arvind Institute of Pharmacy, Jaipur 3

Chapter-1

Introduction

beneficially affects the host animal by improving its intestinal microbial balance". Fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host. In the following decades, intestinal lactic acid bacterial species with alleged health beneficial properties have been introduced as probiotics, including Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus johnsonii.[5]

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-2

PRELIMINARY RESEARCH & POTENTIAL EFFECTS

Chapter-2

Preliminary Research And Potential Effects

PRELIMINARY RESEARCH AND POTENTIAL EFFECTS:

Experiments into the potential health effects of supplemental probiotics include the molecular biology and genomics of Lactobacillus in immune function, cancer, and antibiotic-associated diarrhea, travellers' diarrhea, pediatric diarrhea, inflammatory bowel disease and irritable bowel syndrome. Testing of a probiotic usually applies to a specific strain under study. Diarrhea Some probiotics have been shown in preliminary research to possibly treat various forms of gastroenteritis. They might reduce both the duration of illness and the frequency of stools. Fermented milk products (such as yogurt) also reduce the duration of symptoms. [6] Antibiotic-associated Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as Clostridium difficile. Probiotic treatment might reduce the incidence and severity of AAD as indicated in several meta-analyses. For example, treatment with probiotic formulations including Lactobacillus rhamnosus may reduce the risk of antibiotic-associated diarrhea, improve stool consistency during antibiotic therapy, and enhance the immune response after vaccination. However, further documentation of these findings through randomized, double blind, placebo-controlled trials are required to confirm specific effects and attain regulatory approval, which currently does not exist. Potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage. Up to a 50% reduction of AAD occurrence has been found in preliminary studies. No side-effects have been reported in any of these studies. Maharishi Arvind Institute of Pharmacy, Jaipur 5

Chapter-2

Preliminary Research And Potential Effects

Caution should, however, be exercised when administering probiotic supplements to immunocompromised individuals or patients who have a compromised intestinal barrier. Lactose intolerance As lactic acid bacteria actively convert lactose into lactic acid, ingestion of certain active strains may help lactose intolerant individuals tolerate more lactose than they would otherwise have tolerated.[7] Colon cancer In laboratory investigations, some strains of LAB (Lactobacillus delbrueckii subsp. bulgaricus) have demonstrated anti-mutagenic effects thought to be due to their ability to bind with heterocyclic amines, which are carcinogenic substances formed in cooked meat. Animal studies have demonstrated that some LAB have evidence for acting against colon cancer in rodents, though human data are inconclusive. Some human trials hypothesize that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called -glucuronidase[8] (which can generate carcinogens in the digestive system). Lower rates of colon cancer among higher consumers of fermented dairy products have been observed in one population study, but confirmation of such an effect does not exist. Cholesterol Animal studies have demonstrated the efficacy some strains of LAB to be able to lower serum cholesterol levels, presumably by breaking down bile in the gut, thus inhibiting its reabsorption (which enters the blood as cholesterol). A meta-analysis that included five double blind trials examining the short term (28weeks) effects of a yogurt with probiotic strains on serum cholesterol levels found a minor change of 8.5 mg/dL (0.22 mmol/L) (~4% decrease) in total cholesterol

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-2

Preliminary Research And Potential Effects

concentration, and a decrease of 7.7 mg/dL (0.2 mmol/L) (~5% decrease) in serum LDL concentration. A slightly longer study evaluating the effect of a yogurt with probiotic strains on twenty-nine subjects over six months found no statistically significant differences in total serum cholesterol or LDL values. However, the study did note a significant increase in serum HDL from, 50 mg/dL (1.28 mmol/L) to 62 mg/dL (1.6 mmol/L) following treatment. This corresponds to a possible improvement of LDL/HDL ratio. Studies specifically on hyper-lipidemic subjects are still needed. Blood pressure Although not a confirmed effect, some studies have indicated that consumption of milk fermented with various strains of LAB may result in modest reductions in blood pressure, an effect possibly related to the ACE inhibitor-like peptides produced during fermentation.[7] Immune function and infections Some strains of LAB may affect pathogens by means of competitive inhibition (i.e., by competing for growth) and there is evidence to suggest that they may improve immune function by increasing the number of IgA-producing plasma cells, increasing or improving phagocytosis as well as increasing the proportion of T lymphocytes and Natural Killer cells. Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections and dental caries in children. LAB products might aid in the treatment of acute diarrhea, and possibly affect rotavirus infections in children and travelers' diarrhea in adults, but no products are approved for such indications. A 2010 study suggested that probiotics, by introducing "good" bacteria into the gut, may help maintain immune system activity, which in turn helps the body react more

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-2

Preliminary Research And Potential Effects

quickly to new infections. Antibiotics seem to reduce immune system activity as a result of killing off the normal gut bacteria. [7] Helicobacter pylori Some strains of LAB may affect Helicobacter pylori infections (which may cause peptic ulcers) in adults when used in combination with standard medical treatments, but there is no standard in medical practice or regulatory approval for such treatment. Inflammation Some strains of LAB may modulate inflammatory and hypersensitivity responses, an observation thought to be at least in part due to the regulation of cytokine function. Clinical studies suggest that they can prevent reoccurrences of inflammatory bowel disease in adults, as well as improve milk allergies. They are not effective for treating eczema, a persistent skin inflammation. How probiotics may influence the immune system remains unclear, but a potential mechanism under research concerns the response of T lymphocytes to pro-inflammatory stimuli. Bacterial growth under stress In a study done to see the effects of stress on intestinal flora, rats that were fed probiotics had little occurrence of harmful bacteria latched onto their intestines compared to rats that were fed sterile water. Irritable bowel syndrome and colitis In one study, a commercial strain of bifidobacterium infantis improved some symptoms of irritable bowel syndrome in women. A separate small study showed that a strain of Lactobacillus plantarum, may also be effective in reducing IBS symptoms. A study focused on Bifidobacterium animalis showed a reduction in discomfort and bloating in individuals with constipation-predominant IBS, as well as helping to normalize stool frequency in said individuals. For maintenance of remission of

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-2

Preliminary Research And Potential Effects

ulcerative colitis, Mutaflor (E.coli Nissle 1917) randomized clinical studies showed equivalence of Mutaflor and mesalazine (5-ASAs). [9] Other A study in 2004 testing the immune system of students given either milk or Actimel over a 6-week exam period (3 weeks of studying, 3 weeks of exams) tested 19 different biomarkers. Of these 19 biomarkers, only 2 were shown to be different between the two groups, increased production of lymphocytes, and increased production of CD56 cells. The tests were not blind and show that certain probiotic strains may have no overall effect on the immune system or on its ability. A 2007 study at University College Cork in Ireland showed that a diet including milk fermented with Lactobacillus bacteria prevented Salmonella infection in pigs.[10] A 2007 preliminary study at Imperial College London showed that a commercially available probiotic drink containing Lactobacillus casei DN-114001 and yoghurt bacteria might reduce the incidence of antibiotic-associated diarrhea and C difficileassociated diarrhea. The efficacy and safety of a daily dose of Lactobacillus acidophilus CL1285 in affecting AAD was demonstrated in one preliminary study of hospitalized patients. A 2011 study found that mice given Lactobacillus rhamnosus JB-1 showed lower levels of stress and anxiety than controls. [11] Current research is focusing on the molecular biology and genomics of Lactobacillus strains and bifidobacteria. The application of modern whole genome approaches is providing insights into bifidobacterial evolution, while also revealing genetic functions that may explain their presence in the particular ecological environment of the gastrointestinal tract.[12][13]

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-3

FACTORS AFFECTING VIABILITY IN FOODS

Chapter-3

Factors Affecting Viability In Foods

FACTORS AFFECTING VIABILITY IN FOODS:

Some factors, both intrinsic and extrinsic, may influence the survival of probiotics in food, and so have to be considerated in all stages of probiotic food manufacturing.

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 or pH Interactions with other product components, that can be inhibitory or protective.

Physiological state The physiological state of bacteria when prepared and remaining in a product itself are important factors for survival of the probiotics. Dryness in a food product keeps the bacteria in a relatively quiescent state during storage, while a wet product establishes potentially active metabolism. Temperature affects shelf life of the bacteria, with low temperature providing conditions for possible long term survival. Bacteria can respond to stressful environments by the induction of various stress tolerance mechanisms. One of them is the induction of stress proteins by exposure of the cells to sublethal stresses so they can condition probiotics to better tolerate environmental stresses in food production, storage, and gastrointestinal transit. Different probiotic strains have their own intrinsic tolerances to environmental conditions, including how the culture is prepared, and some cross-protection can be observed, providing protection against other stresses by the exposure to only one stress. Stress responses can be explored to make probiotic strains more resilient and likely to survive in food matrices, with significant industrial importance.

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Chapter-3 Temperature

Factors Affecting Viability In Foods

The temperature at which probiotic organisms grow is an important factor in food applications where fermentation is required, is also a critical factor influencing probiotic survival during manufacture and storage. As it is told above, the lower the temperature the more stable probiotic viability in the food product will be. During processing, temperatures over 4550C will be detrimental to probiotic survival, this means that the higher the temperature, the shorter the time period of exposure required to severely decrease the numbers of viable bacteria, ranging from hours or minutes at 4555C to seconds at higher temperatures. Therefore it is obvious that probiotics should be added downstream of heating/cooking/pasteurization processes in food manufacture to avoid the high temperatures. Elevated temperature also has a detrimental effect on stability during the product process of shipping and storage. Again, the cooler a product can be maintained, the better probiotic survival will be, like in vegetative probiotic cells in liquid products, where refrigerated storage is usually essential. If the product is dried, the bacteria will be in a quiescent state, so acceptable probiotic viability can be maintained in dry products stored at ambient temperatures for 12 months or more. Producing and maintaining low water activities in the foods is the key to maintaining probiotic viability during nonrefrigerated storage because there is a remarkable interaction between temperature and water activity. pH Some bacteria like Lactobacilli and bifidobacteria can tolerate lower pH levels because they produce organic acid and products from carbohydrate metabolism. Indeed, numerous in vitro and in vivo studies have demonstrated that in gastric transit where the cells are exposed to low pH values and with a time of exposure relatively short, some probiotic organisms can survive. In fermented milks and yogurts with pH values between 3.7 and 4.3. lactobacilli are able to grow and survive, while Bifidobacteria tend to be less acid tolerant, with most species surviving poorly in fermented products at pH levels below 4.6. B. animales subsp. lactis is most Maharishi Arvind Institute of Pharmacy, Jaipur 11

Chapter-3

Factors Affecting Viability In Foods

commonly used in acidic foods because is more acid tolerant than human intestinal species, and B. thermoacidophilum, is even more tolerant to low pH (and heat), but has not yet been characterized thoroughly for probiotic traits and is not used commercially. Regarding to fruit juices (pH 3.54.5) commercially successful products have been produced, such as Gefilus (Valio Ltd, Finland), which contains Lactobacillus rhamnosus GG. The viability at low pH can be improved with carriers such as dietary fibers. Survival of lactobacilli in low pHs has also been enhanced in the presence of metabolizable sugars, that allow cell membrane proton pumps to operate and prevent lowering of intracellular pH. This can improve survival during gastric transit, but may not be applicable to improving probiotic survival over the time stages of shelfstorage. Water activity For quiescent probiotic bacteria, water activity is a crucial determinant of survival in food products during storage. The higher moisture levels and water activity, the lower survival of probiotics. There is a substantial interaction between water activity and temperature with respect to their impact on the survival of quiescent probiotics. As the storage temperature is increased, the detrimental impact of moisture is magnified. Here, the osmotic stresses appear to play a role, with the presence of smaller molecules resulting in poorer bacterial survival, although the exact cell death mechanisms have not been elucidated yet. There may be technological limitations to reducing water activity to low levels for improving survival. These include the energy costs of drying, adverse impacts on the taste of foods and difficulties in wetting and dispersing powders. Moisture barrier packaging may be applied to prevent the development of moisture from the environment during storage. Maintaining probiotic viability in moderate water activity foods (0.40.7) is a great challenge and solutions such as microencapsulation

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Chapter-3

Factors Affecting Viability In Foods

or incorporation of probiotics into fat phases of products can provide improved survival. Oxygen Both bifidobacteria and lactobacilli are considered strict anaerobes and oxygen can be detrimental to its growth and survival. However, the degree of oxygen sensitivity varies considerably between different species and strains, for example, lactobacilli, which are mostly microaerophilic, are more tolerant of oxygen than bifidobacteria, to the point where oxygen levels are not an important consideration in maintaining the survival of lactobacilli. Most probiotic bifidobacteria do not grow well in the presence of oxygen, although, many bifidobacteria have enzymatic mechanisms to limit the oxygen toxicity. For oxygen sensitive strains, some strategies can be used to prevent oxygen toxicity in food products. Antioxidant ingredients have been shown to improve probiotic survival, as well as the use of oxygen barrier or modified-atmosphere packaging. Therefor, it is advisable to minimize processes that are highly aerating, particularly when using bifidobacteria. Toxicity of ingredients Interactions between probiotics and other ingredients could happen and those interactions can be protective, neutral, or detrimental to probiotic stability. Obviously, the inclusion of antimicrobial preservatives can inhibit probiotic survival and elevated levels of ingredients such as salt, organic acids, and nitrates can inhibit probiotics during storage, while starter cultures can sometimes inhibit the growth of probiotics during fermentation through the production of specific bacteriocins. Growth factors, protective, and synergistic ingredients Probiotic lactobacilli and, in particular, bifidobacteria are only weakly proteolytic and grow relatively slowly or poorly in milk. The growth of bifidobacteria can be Maharishi Arvind Institute of Pharmacy, Jaipur 13

Chapter-3

Factors Affecting Viability In Foods

improved by the presence of suitable companion cultures, which can aid in protein hydrolysis and through the production of growth factors. Some growth substrates such as carbon sources, nitrogen sources, and growth factors or antioxidants, minerals, and vitamins can be added to improve growth. Finally, the food matrix itself can be protective like in the cheese, where the anaerobic environment, high fat content and buffering capacity of the matrix helps to protect the probiotic cells both in the product and during intestinal transit. Freezethawing The damages made to cell membranes freezing probiotics is detrimental to survival, and also can make the cells more vulnerable to environmental stresses. To prevent or at least mitigate cell injury, protectants are usually added to cultures to be frozen or dried. Once frozen, probiotics can survive well over long shelf lives in products such as frozen yogurts and ice-cream. Using alternative methods of freezing, such as slowcooling rates or pre-freezing stress, can significantly improve cell survival. Repeated freezethawing cycles are highly detrimental to cell survival and should be avoided. Shear forces Probiotic lactobacilli and bifidobacteria are Gram-positive bacteria with thick cell walls that are able to tolerate the shear forces generated in most standard food production processes such as high-speed blending or homogenization, that may result in cell disruption and losses in viability.[14]

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Chapter-4

TYPES OF PROBIOTICS

Chapter-4

Types Of Probiotics

TYPES OF PROBIOTICS:
Probiotic products contain bacteria and/or yeasts that assist in restoring the balance in our gut. Up until the 1960s, the gut microflora that they were able to identify were clostridia, lactobacilli, enterococci, and Escherichia coli. Since then, innovative techniques have discovered many more bacteria. There are several different kinds of probiotics, and their health benefits are determined by the job that they do in your gut. Probiotics must be identified by their genus, species, and strain level. Here is a list of probiotics and their possible health benefits. 1. Lactobacillus There are more than 50 species of lactobacilli. They are naturally found in the digestive, urinary, and genital systems. Foods that are fermented, like yogurt, and dietary supplements also contain these bacteria. Lactobacillus has been used for treating and preventing a wide variety of diseases and conditions. Some of the lactobacilli found in foods and supplements are Lactobacillus acidophilus, L. acidophilus DDS-1, Lactobacillus blugaricus, Lactobacillus rhamnosus GG, Lactobacillus plantarium, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus gasseri. More research is needed regarding probiotics and their potential health benefits before any definitive claims can be made about their effects. However, studies have shown some benefits linked to Lactobacillus and treating and/or preventing yeast infections, urinary tract infection, irritable bowel syndrome, antibiotic-related diarrhea, traveler's diarrhea, diarrhea resulting from Clostridium difficile, treating lactose intolerance, skin disorders (fever blisters, eczema, acne, and canker sores), and prevention of respiratory infections. More specifically, results from some of the studies are as follows:

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Chapter-4

Types Of Probiotics

Lactobacillus GG was given to children 5 to 14 years of age with irritable bowel syndrome over eight weeks' time. They were given 3 billion cells twice per day. This reduced the frequency and severity of abdominal pain.

Lactobacillus GG was given to children taking antibiotics and there was a decrease in reported diarrhea. Lactobacillus casei, Lactobacillus bulgarius, and Streptococcus thermophilus given twice daily during antibiotic treatment and for a week later decreased the risk of diarrhea in hospitalized adults.

Lactobacillus GG-containing milk was given to children 1 to 6 years of age who attended day care. They got fewer or less severe lung infections than those who did not drink it.

Lactobacillus gasseri and Lactobacillus rhamnosus vaginal capsules lengthened the time in between bacterial vaginosis infections. Lactobacillus GG reduced the risk of traveler's diarrhea by 47% in a study with 245 people who traveled to 14 worldwide geographic regions.

2. Bifidobacteria There are approximately 30 species of bifidobacteria. The make up approximately 90% of the healthy bacteria in the colon. They appear in the intestinal tract within days of birth, especially in breastfed infants. Some of the bifidobacteria used as probiotics are Bifodbacterium bifidum, Bifodbacterium Bifodbacterium pseudolongum. As with all probiotics, more research is needed to prove a definitive benefit, but studies have shown that bifidobacteria can help with IBS, dental cavities, improved blood lipids, and glucose tolerance.

lactis, infantis,

Bifodbacterium Bifodbacterium

longum,

Bifodbacterium and

breve,

thermophilum,

Bifodbacterium

Bifidobacterium infantis 35624 was given to 362 patients with irritable bowel syndrome in a four-week study. They showed improvement in the symptoms

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Chapter-4

Types Of Probiotics

of abdominal pain, bloating, bowel dysfunction, incomplete evacuation, straining, and the passage of gas.

Salivary levels of bifidobacteria are associated with dental cavities in adults and children. Bifidobacterium lactis Bb12 is reported to have beneficial effects on metabolism, including lowered serum LDL-cholesterol in people with type 2 diabetes, increased HDL in adult women, and improved glucose tolerance during pregnancy.

3. Saccharomyces boulardii This is also known as S. boulardii and is the only yeast probiotic. Some studies have shown that it is effective in preventing and treating diarrhea associated with the use of antibiotics and traveler's diarrhea. It has also been reported to prevent the reoccurrence of Clostridium difficile, to treat acne, and to reduce side effects of treatment for Helicobacter pylori. 4. Streptococcus thermophilus This produces large quantities of the enzyme lactase, making it effective, according to some reports, in the prevention of lactose intolerance. 5. Enterococcus faecium This is normally found in the intestinal tract of humans and animals. a. E. faecium SF68 b. E . faecium M-74 6. Leuconostoc This has been used extensively in food processing throughout human history, and ingestion of foods containing live bacteria, dead bacteria, and metabolites of these microorganisms has taken place for a long time. Maharishi Arvind Institute of Pharmacy, Jaipur 17

Chapter-4 Probiotic Research and Producer Information[15,16,17,18,19,]

Types Of Probiotics

Strain

Brandname

Producer

Claimed

potential

effect in humans May abdominal improve pain and

Bacillus

coagulans

GBI-30, 6086

GanedenBC30

Ganeden Biotech

bloating in IBS patients. May increase immune response challenge. Human studies have to a viral

Bifidobacterium BB-12

Probio-Tec 12

shown that BB-12 alone BB- Chr. Hansen or in combination may have an effect on the gastrointestinal system. In one preliminary for and

animalis subsp. lactis Bifidobacterium

study, showed possible Bifidobacterium infantis 35624 Align Procter Gamble & improvement abdominal pain/discomfort bowel difficulty. Shown in one study to Danisco reduce the side effects of antibiotic therapy. movement

Lactobacillus acidophilus NCFM

Lactobacillus paracasei St11 (or

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Chapter-4 NCC2461) Lactobacillus johnsonii La1 (= LC1, Nestl Lactobacillus Lactobacillus johnsonii NCC533)

Types Of Probiotics

May reduce incidence of H pylori-caused gastritis and may reduce inflammation

Lactobacillus plantarum 299v

GoodBelly/ProViva/Pr obiMage

May improve symptoms Probi of IBS; however, more research is required. Preliminary evidence

Lactobacillus American Culture

reuteri Type BioGaia

for diarrhea mitigation in children, H. pylori infection, effect on possible gingivitis,

Collection|ATTC 55730 (Lactobacillus reuteri SD2112)

fever in children and number of sick days in adults.

Lactobacillus daughter

reuteri of

Protectis (DSM 17938, strain ATCC 55730) Limited evidence for treatment diarrhea. of acute

Saccharomyces boulardii

DiarSafe and others

Wren Laboratories

tested

as

mixture:

Lactobacillus rhamnosus GR-1 &

Bion Intime/Jarrow

In one study, oral Flore Chr. Hansen ingestion resulted in Femvaginal colonisation and 19

Maharishi Arvind Institute of Pharmacy, Jaipur

Chapter-4 Lactobacillus RC-14 tested as mixture: American reuteri Dophilus

Types Of Probiotics reduced vaginitis.

Lactobacillus acidophilus NCFM & Florajen3 Bifidobacterium bifidum BB-12

Preliminary Lifeline, Inc associated (CDAD).

evidence disease

for reduced C. difficile

May health.

affect

digestive

In vitro inhibition of Listeria monocytogenes tested as mixture: Bio-K+ casei l and L. innocua, coli, faecalis Lactobacillus acidophilus CL1285 & Bio-K+ CL1285 Lactobacillus LBC80R Escherichia Enterococcus and faecium. Reduction of symptoms of lactose intolerance and stimulation. Lactobacillus plantarum HEAL 9 & Bravo Lactobacillus paracasei 8700:2 ProbiFrisk Friscus/ Probi Is under study for cold immune

Internationa Staphylococcus aureus, Enterococcus

common infections.

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Chapter-4 Some additional forms of lactic acid bacteria include:

Types Of Probiotics

Lactobacillus bulgaricus Streptococcus thermophilus "Lactobacillus bifidus" - became new genus Bifidobacterium

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

MULTI-PROBIOTIC:
Preliminary research is evaluating the potential physiological effects of multiple probiotic strains, as opposed to a single strain. As the human gut may contain several hundred microbe species, one theory indicates that this diverse environment may benefit from consuming multiple probiotic strains, an effect that remains scientifically unconfirmed. [19]

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Chapter-5

HEALTH BENEFITS OF PROBIOTICS

Chapter-5

Health Benefits Of Probiotics

HEALTH BENEFITS OF PROBIOTICS:

Probiotics may seem new to the food and supplement industry, but they have been with us from our first breath. During a delivery through the birth canal, a newborn picks up bacteria from his/her mother. These good bacteria are not transmitted when a Cesarean section is performed and have been shown to be the reason why some infants born by Cesarean section have allergies, less than optimal immune systems, and lower levels of gut microflora. Probiotics are believed to protect us in two ways. The first is the role that they play in our digestive tract. We know that our digestive tract needs a healthy balance between the good and bad bacteria, so what gets in the way of this? It looks like our lifestyle is both the problem and the solution. Poor food choices, emotional stress, lack of sleep, antibiotic overuse, other drugs, and environmental influences can all shift the balance in favor of the bad bacteria. When the digestive tract is healthy, it filters out and eliminates things that can damage it, such as harmful bacteria, toxins, chemicals, and other waste products. On the flip side, it takes in the things that our body needs (nutrients from food and water) and absorbs and helps deliver them to the cells where they are needed. The idea is not to kill off all of the bad bacteria. Our body does have a need for the bad ones and the good ones. The problem is when the balance is shifted to have more bad than good. An imbalance has been associated with diarrhea, urinary tract infections, muscle pain, and fatigue. The other way that probiotics help is the impact that they have on our immune system. Some believe that this role is the most important. Our immune system is our protection against germs. When it doesn't function properly, we can suffer from allergic reactions, autoimmune disorders (for example, ulcerative colitis, Crohn's disease, and rheumatoid arthritis), and infections (for example, infectious diarrhea, Helicobacter pylori, skin infections, and vaginal infections). By maintaining the correct balance from birth, the hope would be to prevent these ailments. Our immune system can benefit anytime that balanced is restored, so it's never too late.[20]

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Chapter-6

WHAT FOODS CONTAIN PROBIOTICS?

Chapter-6

What Foods Contain Probiotics?

WHAT FOODS CONTAIN PROBIOTICS?

Fermented dairy products have been advertised as containing "beneficial cultures." These cultures are what would now be considered probiotics. Other foods currently claiming to provide probiotics are cereal, juice, frozen yogurt, granola, candy bars, and cookies. While they may contain probiotics, there is no guarantee that they have them in the amount or in the form that is necessary to get the health benefits you are looking for. Only the manufacturer of the product can tell you if there are any studies to support their specific product. Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders and sachets containing the bacteria in freeze dried form are also available. Few of the strains presented have been sufficiently developed in basic and clinical research to warrant application for health claim status to a regulatory agency such as the Food and Drug Administration or European Food Safety Authority, but so far no claims have been approved.[15]

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Chapter-7

HOW SHOULD PEOPLE TAKE PROBIOTICS?

Chapter-7

How Should People Take Probiotics?

HOW SHOULD PEOPLE TAKE PROBIOTICS?

The requirements for a microbe to be considered a probiotic are that the microbe must be alive when administered, it must be documented to have a heath benefit, and it must be administered at levels to confer a health benefit. These are live microorganisms that will not provide the promised benefits if they don't stay alive. The manufacturer and consumer must pay close attention to the conditions of storage at which the particular microorganism will survive and the end of their shelf life. The potency will tell you the number of viable bacteria per dose, and the purity has to do with presence of contaminating or ineffective bacteria. The other thing to remember is that these microorganisms are not all created equally. In fact, the genus, strain, and species all need to be the same for the results that you find in the study to be the results that you hope to achieve when taking it. For example, with the strain Lactobacillus rhamnosus GG, the genus is Lactobacillus, the species is rhamnosus and the strain is GG. If any one of those are different in your supplement, you may not attain the same results. With the growing popularity of probiotics, there is a huge variety of supplements from which you can choose. The most important thing is to determine what type of probiotic microorganism you need for your condition. Do not just take the supplement that provides the most kinds of organisms. You need to do your research and be sure that there are scientific studies to support what you take. New research is emerging, so if you don't find what you need right, now keep looking. Your doctor can help you decide if trying probiotics might be helpful for you and can advise you regarding the amount and type of probiotics that may be appropriate in your case.[20]

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Chapter-8

THE SIDE EFFECTS AND RISKS OF PROBIOTICS

Chapter-8

The Side Effects And Risks Of Probiotics

THE SIDE EFFECTS AND RISKS OF PROBIOTICS: In some situations, such as where the person consuming probiotics is critically ill, probiotics could be harmful. In a therapeutic clinical trial conducted by the Dutch Pancreatitis Study Group, the consumption of a mixture of six probiotic bacteria increased the death rate of patients with predicted severe acute pancreatitis. In a clinical trial conducted at the University of Western Australia, aimed at showing the effectiveness of probiotics in reducing childhood allergies, researchers gave 178 children either a probiotic or a placebo for the first six months of their life. Those given the good bacteria were more likely to develop a sensitivity to allergens. Some hospitals have reported treating lactobacillus septicaemia, which is a potentially fatal disease caused by the consumption of probiotics by people with lowered immune systems or who are already very ill. [21] There is no published evidence that probiotic supplements are able to replace the body's natural flora when these have been killed off; indeed bacterial levels in feces disappear within days when supplementation ceases. Probiotics taken orally can be destroyed by the acidic conditions of the stomach. A number of micro-encapsulation techniques are being developed to address this problem. Recent studies indicate that probiotic products such as yogurts could be a cause for obesity trends. However, this is contested as the link to obesity, and other health related issues with yogurt may link to its dairy and calorie attributes. Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.

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Chapter-8

The Side Effects And Risks Of Probiotics

Supplements are not monitored in the U.S. the way that food or medication is. They fall under the Dietary Supplement Health and Education Act of 1994 (DSHEA). This requires that the dietary supplement or dietary ingredient manufacturer be responsible for ensuring that a dietary supplement or ingredient is safe before it is marketed. The only time that the U.S. Food and Drug Administration (FDA) may get involved is if action is needed to be taken against a manufacturer after the supplement is marketed and then found to be unsafe. This means that as much as we may know about probiotics, we can't be certain of the safety or content of the supplements available to us. There is one Voluntary Certification Program by which a supplement manufacturer can choose to be evaluated. ConsumerLab.com (CL) is the leading provider of independent test results and information to help consumers and health care professionals identify the best quality health and nutrition products. Products that have passed their testing for identity, strength, purity, and disintegration can print the CL Seal of Approval on their product. This is one step toward being confident that you are getting the amount and type of probiotic promised by the manufacturer. [22]

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Chapter-9

EFSA OPINIONS OF PROBIOTICS

Chapter-9

Efsa Opinions Of Probiotics

EFSA OPINIONS OF PROBIOTICS:

The European Food Safety Authority has so far rejected 260 claims on probiotics in Europe due to insufficient research and thus no conclusive proof. This includes:

Lactobacillus paracasei LMG P 22043 does not decrease potentially pathogenic gastro-intestinal microorganisms or reduce gastro-intestinal discomfort.

Lactobacillus johnsonii BFE 6128 . Immunity and skin claims all too general for consideration under the NHCR. Lactobacillus fermentum ME-3 not shown to decrease potentially pathogenic gastro-intestinal microorganisms. Lactobacillus plantarum BFE 1685. Immunity claim deemed too general for NHCR. Bifidobacterium longum BB536 does not improve bowel regularity; does not resist cedar pollen allergens; does not decrease pathogens. Bifidobacterium animalis ssp. lactis Bb-12 does not help maintain normal LDL-blood cholesterol; does not decrease pathogens or boost immunity. Lactobacillus plantarum 299v does not reduce flatulence and bloating or protect DNA, proteins and lipids from oxidative damage. Lactobacillus rhamnosus LB21 NCIMB 40564 does not help maintain individual intestinal microbiota in subjects receiving antibiotic treatment.[5]

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Chapter-10

REFERENCES

References

REFERENCES:
1. Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria (October 2001). "Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria". Food and Agriculture Organization of the United Nations, World Health Organization. Retrieved 2009-11-04. 2. Hamilton-Miller, Professor J. M. T.; G. R. Gibson, W. Bruck. "Some insights into the derivation and early uses of the word 'probiotic'". British Journal of Nutrition 2003 (90): 845. Retrieved 19 November 2009. 3. Metchnikoff, E. 1907. Essais optimistes. Paris. The prolongation of life. Optimistic studies. Translated and edited by P. Chalmers Mitchell. London: Heinemann, 1907. 4. General function health claims under Article 13 at the Wayback Machine (archived August 19, 2010) 5. Vaughan RB (July 1965). "The romantic rationalist: A study of Elie Metchnikoff". Medical History 9: 20115. 6. Ljungh A, Wadstrom T, ed. (2009). Lactobacillus Molecular Biology: From Genomics to Probiotics. Caister Academic Press. 7. Wollowski I, Rechkemmer G, Pool-Zobel BL (February 2001). "Protective role of probiotics and prebiotics in colon cancer". The American Journal of Clinical Nutrition 73 (2 Suppl): 451S455S. 8. Brady LJ, Gallaher DD, Busta FF (February 2000). "The role of probiotic cultures in the prevention of colon cancer". The Journal of Nutrition 130 (2S Suppl): 410S414S. PMID 10721916 9. Kirjavainen PV, Salminen SJ, Isolauri E (February 2003). "Probiotic bacteria in the management of atopic disease: underscoring the importance of viability". J. Pediatr. Gastroenterol. Nutr. 36 (2): 2237.

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References 10. Hickson M, D'Souza AL, Muthu N et al (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhea associated with antibiotics: randomised double blind placebo controlled trial". BMJ 335 (7610): 80. 11. Bravo, Javier et al (August 29, 2011). "Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve". Proceedings of the National Academy of Sciences 108 (38). Retrieved 2 September 2011. 12. Sonomoto, K; Yokota, A (editor) (2011). Lactic Acid Bacteria and Bifidobacteria: Current Progress in Advanced Research. Caister Academic Press. 13. "Incorporating Probiotics into Food". pg. 60-67. Ross Crittenden, in "Handbook of Probiotics and Prebiotics". Y. K. Lee and S. Salminen. 2nd Edition. Ed. Wiley. (2009) 14. Besselink MG, van Santvoort HC, Buskens E et al (February 2008). "Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial". Lancet 371 (9613). 15. Hun, Larysa MD, FAAP, L (2009). "Bacillus coagulans Significantly Improved Abdominal Pain and Bloating in Patients with IBS". Postgraduate Medicine 121 (2): 119124. doi:10.3810/pgm.2009.03.1984. PMID 19332970 16. http://www.chrhansen.com/fileadmin/user_upload/_temp_/Selected_summaries_BB-12.pdf 17. Robinson, R.K., ed. (2007). "Sellars, R.L.". pp. 81116. 18. Sesea, S; Palop, ML; M.Ll. Palop (2007). "An ecological study of lactic acid bacteria from Almagro eggplant fermentation brines". Journal of Applied Microbiology (Blackwell Publishing) 103 (5): 15531561. Retrieved 7 November 2007. Acidophilus Products (Therapeutic Properties of Fermented Milks). Chapman & Hall, London.

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References 19. Ji, Feng-Di; Ji, B.-P.; Li, B.; Han, B.-Z. (2007). "Note. Microbial Changes During the Salting Process of Traditional Pickled Chinese Cabbage". Food Science and Technology International (SAGE Publications) 13 (1): 1116, Retrieved 7 November 2007 20. "Health Benefits of Taking Probiotics." The Harvard Medical School Family Health Guide Sept. 2005. <http://www.health.harvard.edu/fhg/updates/update0905c.shtml>. 21. Bee, Peta (November 10, 2008). "Probiotics, Not so friendly after all". The Times (London). 22. Islam MA, Yun CH, Choi YJ, Cho CS (2010). "Microencapsulation of live probiotic bacteria" (PDF). Journal of Microbiology and Biotechnology 20 (13671377): 13671377.

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