A Project Report on PROBIOTICS Project work submitted for partial fulfillment for the award of bachelor of pharmacy (B.Pharma.) degree. Supervised By: Submitted By: Mr.Sandeep Kataria Shyam Sunder Jayalwal Assit.Professor B.Pharma.Final year MAHARSHI ARVIND INSTITUTE OF PHARMACY, JAIPUR 2011-2012
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 fi
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A
Project Report
on
PROBIOTICS
Project work submitted for partial fulfillment for the award of bachelor of pharmacy (B.Pharma.) degree.
Supervised By: Submitted By:Mr.Sandeep Kataria Shyam Sunder JayalwalAssit.Professor 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 Dr. RAJESH ASIJA
Assistant Professor Principal
MAIP, Jaipur 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 co-
operation, 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 Page No.
1. INTRODUCTION 1-4
2. PRELIMINARY RESEARCH AND POTENTIAL EFFECTS
5-9
3. FACTORS AFFECTING VIABILITY IN FOODS 10-14
4. TYPES OF PROBIOTICS 15-21
5. HEALTH BENEFITS OF PROBIOTICS 22
6. WHAT FOODS CONTAIN PROBIOTICS? 23
7. HOW SHOULD PEOPLE TAKE PROBIOTICS? 24
8. THE SIDE EFFECTS AND RISKS OF PROBIOTICS 25-26
9. EFSA OPINIONS OF PROBIOTICS 27
10. REFERENCES 28-30
Chapter-1
INTRODUCTION
Chapter-1 Introduction
Maharishi Arvind Institute of Pharmacy, Jaipur 1
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 βιωτικός (biotic), the latter deriving from the noun
βίος (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]
Chapter-1 Introduction
Maharishi Arvind Institute of Pharmacy, Jaipur 2
Histry:
Élie Metchnikoff
The original observation of the positive role played by certain bacteria was first
introduced by Russian scientist and Nobel laureate Élie 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
Chapter-1 Introduction
Maharishi Arvind Institute of Pharmacy, Jaipur 3
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
Chapter-1 Introduction
Maharishi Arvind Institute of Pharmacy, Jaipur 4
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]
Chapter-2
PRELIMINARYRESEARCH &
POTENTIALEFFECTS
Chapter-2 Preliminary Research And Potential Effects
Maharishi Arvind Institute of Pharmacy, Jaipur 5
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
Bifodbacterium infantis, Bifodbacterium thermophilum, and 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.
Bifidobacterium infantis 35624 was given to 362 patients with irritable bowel
syndrome in a four-week study. They showed improvement in the symptoms
Chapter-4 Types Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 17
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.
Chapter-4 Types Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 18
Probiotic Research and Producer Information[15,16,17,18,19,]
Strain Brandname ProducerClaimed potential
effect in humans
Bacillus coagulans
GBI-30, 6086GanedenBC30
Ganeden
Biotech
May improve
abdominal pain and
bloating in IBS patients.
May increase immune
response to a viral
challenge.
Bifidobacterium
animalis subsp. lactis
BB-12
Probio-Tec
Bifidobacterium BB-
12
Chr. Hansen
Human studies have
shown that BB-12 alone
or in combination may
have an effect on the
gastrointestinal system.
Bifidobacterium
infantis 35624Align
Procter &
Gamble
In one preliminary
study, showed possible
improvement for
abdominal
pain/discomfort and
bowel movement
difficulty.
Lactobacillus
acidophilus NCFMDanisco
Shown in one study to
reduce the side effects
of antibiotic therapy.
Lactobacillus
paracasei St11 (or
Chapter-4 Types Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 19
NCC2461)
Lactobacillus
johnsonii La1 (=
Lactobacillus LC1,
Lactobacillus
johnsonii NCC533)
Nestlé
May reduce incidence
of H pylori-caused
gastritis and may reduce
inflammation
Lactobacillus
plantarum 299v
GoodBelly/ProViva/Pr
obiMageProbi
May improve symptoms
of IBS; however, more
research is required.
Lactobacillus reuteri
American Type
Culture
Collection|ATTC
55730 (Lactobacillus
reuteri SD2112)
BioGaia
Preliminary evidence
for diarrhea mitigation
in children, H. pylori
infection, possible
effect on gingivitis,
fever in children and
number of sick days in
adults.
Lactobacillus reuteri
Protectis (DSM 17938,
daughter strain of
ATCC 55730)
Saccharomyces
boulardiiDiarSafe and others
Wren
Laboratories
Limited evidence for
treatment of acute
diarrhea.
tested as mixture:
Lactobacillus
rhamnosus GR-1 &
Bion Flore
Intime/Jarrow Fem-Chr. Hansen
In one study, oral
ingestion resulted in
vaginal colonisation and
Chapter-4 Types Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 20
Lactobacillus reuteri
RC-14
Dophilus reduced vaginitis.
tested as mixture:
Lactobacillus
acidophilus NCFM &
Bifidobacterium
bifidum BB-12
Florajen3American
Lifeline, Inc
Preliminary evidence
for reduced C. difficile–
associated disease
(CDAD).
tested as mixture:
Lactobacillus
acidophilus CL1285 &
Lactobacillus casei
LBC80R
Bio-K+ CL1285
Bio-K+
Internationa
l
May affect digestive
health.
In vitro inhibition of
Listeria monocytogenes
and L. innocua,
Escherichia coli,
Staphylococcus aureus,
Enterococcus faecalis
and Enterococcus
faecium.
Reduction of symptoms
of lactose intolerance
and immune
stimulation.
Lactobacillus
plantarum HEAL 9 &
Lactobacillus
paracasei 8700:2
Bravo Friscus/
ProbiFriskProbi
Is under study for
common cold
infections.
Chapter-4 Types Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 21
Some additional forms of lactic acid bacteria include:
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]
Chapter-5
HEALTHBENEFITS OFPROBIOTICS
Chapter-5 Health Benefits Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 22
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 betweenthe 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]
Chapter-6
WHAT FOODSCONTAIN
PROBIOTICS?
Chapter-6 What Foods Contain Probiotics?
Maharishi Arvind Institute of Pharmacy, Jaipur 23
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]
Chapter-7
HOW SHOULDPEOPLE TAKEPROBIOTICS?
Chapter-7 How Should People Take Probiotics?
Maharishi Arvind Institute of Pharmacy, Jaipur 24
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]
Chapter-8
THE SIDEEFFECTS AND
RISKS OFPROBIOTICS
Chapter-8 The Side Effects And Risks Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 25
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.
Chapter-8 The Side Effects And Risks Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 26
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]
Chapter-9
EFSA OPINIONSOF PROBIOTICS
Chapter-9 Efsa Opinions Of Probiotics
Maharishi Arvind Institute of Pharmacy, Jaipur 27
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]
Chapter-10
REFERENCES
References
Maharishi Arvind Institute of Pharmacy, Jaipur 28
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: 201–15.
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): 451S–455S.
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): 410S–414S. 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): 223–7.
References
Maharishi Arvind Institute of Pharmacy, Jaipur 29
10. Hickson M, D'Souza AL, Muthu N et al (2007). "Use of probiotic
Lactobacillus preparation to prevent diarrhea associated with antibiotics: