Probiotics are live bacteria or yeasts that are good for the digestive system.
Prebiotics as non-digestible ingredients in the food that can stimulate the activity of desirable microbiota
2. History of probiotics:
• The history of probiotics began with the
consumption of fermented foods.
Consumption of fermented foods was first
observed in ancient Greeks and Romans.
• In 1907, Ellie Metchnikoff, a Nobel Prize
winner, first proposed the beneficial effects
of probiotic microorganisms on human
health.
• Metchnikoff hypothesized that Bulgarians
were healthy and lived long because of the
consumption of fermented milk products
which consists of rod shaped bacteria
(Lactobacillus spp.).
Ellie Metchnikoff
3. History of probiotics:
• In the Middle Ages, fermented milk and cheese
was mainly produced at the abbeys and
convents, and they appear in the Crusaders’
chronicles; later, we can find them in very
distant populations such as Bulgarian
shepherds, the Hindus, the Calmucchi, in France,
at the court of Franci, the Zulu, the Russians and
other peoples of the Ottoman Empire.
• In 1906 the French Society “Le Fermente” began
to market and sold in pharmacies, according to
the Metchnikoff’s idea of helping children
suffering from diarrhoea. The product obtained
great success among the consumers.
• In 1925 it was sold a product called “yogurt” that
rapidly spread in Europe and North America.
4. History of probiotics:
• In the 20’s, Minoru Shirota, a Japanese
microbiologist at the University of Kyoto
discovered that some bacteria of the intestinal
flora contribute to bacterial pathogens defence ,
afterwards called Lc Shirota.
• The following studies led to isolate and cultivate
Lactobacillus casei (Lc) .
• In 1935 in Japan began the production of a
beverage containing this microorganism, called
Yakult , that over the years was spread
throughout the world.
Minoru Shirota (1899–1982)
5. What is probiotics ?
• Probiotics are live microorganisms which
when administered in adequate amounts
confer a health benefit on the host.
• Kollath in 1953 and Vergio in 1954 were
probably the first to introduce the term
‘Probiotic’ .
• The term ‘probiotic’ was first used in 1965 by
Lilly and Stillwell to describe substances
which stimulate the growth of other
microorganisms.
• Since then the word ‘probiotic’ has been
used in different contexts according to its
mechanism and the affects on human health.
6. What is probiotics ?
• Probiotics have many definitions over the years such as :
• Fuller 1989: A live microbial supplement which affects host’s
health positively by improving its intestinal microbial balance.
• Shaafasma 1996: Living microorganisms, which upon ingestion
in certain numbers, exert health benefits beyond inherent basic
nutrition.
• Salminen et al. 1998: A live microbial food ingredient that is
beneficial to health.
• Naidu et al. 1999: A microbial dietary adjuvant that beneficially
affects the host physiology by modulating mucosal and
systemic immunity, as well as improving nutritional and
microbial balance in the intestinal tract .
7. What is probiotics ?
• Schrezenmeir and de Vrese 2001: A preparation of or a product
containing viable, defined microorganisms in sufficient
numbers, which alter the microflora (by implantation or
colonization) in a compartment of the host and by that exert
beneficial health effects in this host.
• Klaenhammer 2000, Sanders 2003, Guarner et al. 2005: Live
microorganisms which when administered in adequate amounts
confer a health benefit on the host, is accepted by FAO/WHO.
8. The gastrointestinal tract :
• The gastrointestinal tract (GIT) is colonized
by more than 100 trillion microorganisms
known as microbiota and also termed as
microflora.
• The microbiota refers to an entire
population of microorganisms that
colonizes a particular location in GIT, and
composed of not only bacteria, but also
other microbes such as fungi, viruses, and
parasites.
9. The gastrointestinal tract :
• The gut microbiota plays a significant role
in the physiological functions such as
strengthening gut integrity or shaping the
intestinal epithelium harvesting energy,
immune function protecting against
pathogens and health status of the host.
• Microbiota colonizes the human host
instantly after birth and gradually adapts to
the GI environment. This colonization
contains both “friendly” bacteria, such as
Gram-positive Lactobacilli and
Bifidobacteria which are dominant (> 85%
of total bacteria), and potential pathogenic
bacteria.
10. Digestive system and Gut flora(bacteria) :
• Gut bacteria aids in maintaining the normal
physiological functions of the intestines.
• They can assist in the regulation of gut motility,
transformation of steroids and bile acids, production
of vitamins, absorption of minerals, metabolism of
xenobiotic substances.
• Also it helps in the activation and destruction of
toxins, genotoxins, and mutagens.
12. Probiotics and prebiotics(synbiotic) :
• Prebiotics are nondigestible food ingredients that selectively stimulate
the proliferation and/or activity of desirable bacterial populations already
resident in the consumer’s intestinal tract.
• Two major strategies have been proposed to maintain a high level of
probiotics to sustain beneficial health effects; 1) continuous ingestion of
probiotics containing foods or 2) supplementation of food with prebiotics.
• The prebiotic strategy offers a number of advantages over modifying the
intestinal microbiota using probiotics or antibiotics.
• A prebiotic is expected to improve the composition of the colonic
microbiota and through this serve as beneficial to the host health.
• Synbiotic : is a combination of probiotics and prebiotics.
13. Probiotics and prebiotics(synbiotic) :
• History of the development of prebiotics :
• 1900-Tissier described bifidobacteria (Bacillus bifidus) in the feces of
babies.
• 1906-Tissier proposed the oral feeding of bifidobacteria to prevent infant
diarrhea.
• 1954-Gyorgy reported that components of human milk (N-acetyl-
glucosamine) promoted the growth of a Bifidobacterium strain.
• 1957-Petuely recognized lactulose as a “bifidus” factor.
• 1970s–1980s-Japanese researchers discovered that a number of different
nondigestible oligosaccharides were “bifidus” factors.
• 1995-The term “prebiotic” coined by Gibson and Roberfroid to link the
concepts of prebiotics and probiotics for promoting beneficial populations
of intestinal bacteria.
14. Probiotics and prebiotics(synbiotic) :
• The main reason of prebiotics supplementation to human diet is to
beneficially enhance the gut microflora, which is Bifidobacterium spp., the
most dominant and important flora in breast-fed and healthy infants.
• Their growth is dependent on the presence of complex carbohydrates
known as oligosaccharides.
• Some oligosaccharides, because of their chemical structure, are
resistant to digestive enzymes and therefore pass into the large intestine.
• Therefore, prebiotics are used as bifidogenic factors in diet applications,
especially because of their ability not to degrade in the stomach and
small intestine.
15. Probiotics and prebiotics(synbiotic) :
• TYPES OF PREBIOTICS:
• Nondigestible (or only partially digested).
• Nonabsorbable in the small intestine.
• Poorly fermented by bacteria in the mouth.
• Well fermented by purportedly beneficial bacteria in the gut.
• Poorly fermented by potentially pathogenic bacteria in the gut.
17. Probiotics and prebiotics(synbiotic) :
• Other types include :
• Lactulose, (prebiotics).
• Lactitol, (potentil prebiotic).
• Xylooligosaccharides, (potential prebiotic).
• Isomaltooligosaccharides, (potential prebiotic).
• Soybean oligosaccharides (raffinose and stachyose), (potential prebiotic).
18. Probiotics and prebiotics(synbiotic) :
• Advantages of prebiotics over probiotics:
• Stable in long shelf life foods and beverages.
• Heat and pH stable and can be used in a wide range of
processed foods and beverages.
• Have physicochemical properties useful to food taste and
texture.
• Resistant to acid, protease, and bile during intestinal passage.
• Stimulate organisms already resident in the host, and so avoid
host/strain compatibilities, and the need to compete with an
already established microbiota.
• Stimulate fermentative activity of the microbiota and health
benefits from SCFA (short chain fatty acids).
• Lower intestinal pH and provide osmotic water retention in the
gut.
19. Probiotics and prebiotics(synbiotic) :
• Advantages of prebiotics over antibiotics:
• Safe for long-term consumption and prophylactic
approaches.
• Do not stimulate side effects such as antibiotic-
associated diarrhea, sensitivity to UV radiation, or liver
damage.
• Do not stimulate antimicrobial resistance genes.
• Not allergenic.
20. Probiotics and prebiotics(synbiotic) :
• Disadvantages of prebiotics:
• Unlike probiotics, overdose can cause intestinal
bloating, pain, flatulence, or diarrhea.
• Not as potent as antibiotics in eliminating specific
pathogens.
• May exacerbate side effects of simple sugar
malabsorption during active diarrhea.
21. Probiotics and prebiotics(synbiotic) :
• The probiotic concept is open to lots of different
applications in a large variety of fields relevant for
human and animal health.
• Probiotic products consist of different enzymes,
vitamins, capsules or tablets and some fermented
foods contain microorganisms which have
beneficial effects on the health of the host.
• Probiotics have been used in many medical
applications for the improvement of human health ,
it also used as supplements to raise the immunity
and improve the body overall health (especially the
gut health).
22.
23. Isolation of probiotics strains :
• Various potential probiotic
microorganisms could be isolated
from:
• The mouth.
• Gastrointestinal (GI) content.
• Feces of animal and human.
• It can be isolated from human
milk.
• Isolation from fermented food.
24. Selection of probiotics strains :
• The selection of probiotic strains depends on many criteria :
• Manufacturing Criteria (General Criteria):
• (a)Ease in maintaining in storage without loss of viability.
• (b)Ability to revitalize and grow quickly to the maximum
concentration in a simple and cheap fermentation medium.
• (c)Ability to grow and survive in microaerophilic or aerobic
conditions.
• (d)Ability to withstand physical handling without significant
loss of viability.
• (e)Ability to survive in the food matrices and during
processing.
25. Selection of probiotics strains :
• Shelf Life and Gut Transit (General
Criteria):
• Tolerance to Digestive Juices.
• Adhesion and Colonization onto Specific Site
of Body Surface.
• Surviving the acid conditions of the stomach
and bile salts.
26. Selection of probiotics strains :
• Health Properties (Specific Criteria):
• (a)Ability to utilize prebiotics for growth.
• (b)Ability to synthesize vitamins .
• (c)Ability to inhibit or exclude pathogens.
• (d)Antibiotic resistance across a wide
range of antibiotics. Antibiotic resistance
would allow the probiotics to be used with
antibiotic administration to prevent
antibiotic-associated diarrhea. However,
there is a concern on transfer of antibiotic
resistance genes.
27. Selection of probiotics strains :
• (e)Ability to synthesize b-galactosidase.
• (f)Ability to deconjugate bile acid.
• (g)Ability to produce antimicrobial
substances.
• (h)Ability to modulate immune reactions.
28. Identification of probiotics strains :
• Phenotypic methods :
Differential plating: used to
differentiate closely related
organisms or groups of organisms.
Carbohydrate fermentation-based
methods: used to determine
whether or not a bacteria can
utilize certain carbohydrate.
29. Identification of probiotics strains :
Spectroscopic methods: by
employing light to interact with
matter and thus probe certain
features of a sample to learn about
its consistency or structure.
Fluorescence dyes-based methods:
fluorescent dyes are usually
targeted to proteins of interest by
antibody conjugates or peptide tags.
30. Identification of probiotics strains :
• Genetic methods :
• Polymerase chain reaction-based methods:
used to rapidly make millions to billions of
copies of a specific DNA sample , PCR allows
for rapid and highly specific identification of
bacterial strains.
• DNA banding pattern-based methods: pattern
of light and dark transverse bands on a
stained chromosome and describes the
location of genes.
31. Identification of probiotics strains :
• DNA sequencing-based methods: used to
determine the nucluetides sequence
of DNA.
• Probe hybridisation methods: fragment of
DNA or RNA of variable length (usually 100–
10000 bases long) which can be
radioactively or fluorescently labeled, it can
then be used in DNA or RNA samples to
detect the presence of nucleotide
substances (the RNA target) that are
complementary to the sequence in the
probe.
32. Probiotics applications:
• Probiotics were originally used to improve
the health of both animals and humans
through the modulation of the intestinal
microbiota.
• Probiotics have many applications includes :
• Probiotics for human health, and Potential
pharmaceutical applications.
• Probiotics in infant nutrition.
• Probiotics for elderly.
• Probiotics in animal nutrition.
33. Mechanism of probiotics action:
• Before we talk about the probiotics applications , we
must understand the mechanisms of probiotics action
which make them useful and effective :
• 1. Receptor competition, whereby probiotics compete
with microbial pathogens for limited number of
receptors present on the surface of the intestinal
epithelium.
• 2. Probiotics release antimicrobial compounds, such as
organic acids, free fatty acids, hydrogen peroxide, and
bacteriocins, which may induce an antagonistic action
against pathogenic organism.
34. Mechanism of probiotics action:
• 3. Increased induction of mucin secretion, which
results in enhanced binding of probiotics to the
intestinal mucosa. This action blocks enteropathogen
binding to epithelial receptors.
• 4. Competition for nutrients in the GIT .
• 5. Possible modification of toxin receptors and
blockage of toxin-mediated pathology by probiotics.
35. Mechanism of probiotics action:
• 6. Possible promotion by probiotics of nonspecific
stimulation of the host immune system, including immune
cell proliferation, enhanced phagocytic activity of
macrophages, and increased production of secretory
immunoglobulin A (IgA) and IgM.
• 7. Stabilization of intestinal permeability barrier, which
restricts colonization by pathogens, eliminates foreign
antigens, which have penetrated the mucosa, and regulates
the antigen-specific immune responses.
• 8. Probiotic bacterial “priming” of gut-associated lymphoid
tissue (GALT) and immunomodulation of gut-associated
lymphoid and epithelial tissue response.
36. Potential pharmaceutical applications
(Intestinal Disorders):
• Antibiotic-Associated Diarrhea (AAD) :
• Most cases of AAD are directly or indirectly caused
by alterations of gut microflora by the antibiotics
resulting in functional disturbances of intestinal
carbohydrate or bile acid metabolism.
• probiotic supplementation modulates the response
of the intestinal microflora to the effects of
antibiotic therapy. Lactobacillus rhamnosus GG has
been shown to reduce the risk of AAD by
approximately 75 percent in children in studies
carried out in the United States and Finland.
• Lactobacilli, especially Lactobacillus rhamnosus GG
, have been reported to be beneficial in AAD.
37. Potential pharmaceutical applications
(Intestinal Disorders):
• Radiotherapy-Induced Diarrhea:
• Disruption of morphologic mucosal integrity and
normal bacterial microflora after abdominal
radiation leads to malabsorption and bacterial
translocation.
• Probiotics added as substrates can be given by
an oral or enteral route to patients, who undergo
radiotherapy to prevent radiation-induced
enteritis, diarrhea, and related malnutrition.
• In patients undergoing abdominal irradiation, the
prevention of intestinal diarrhea (side effect)
was obtained by the administration of live L.
acidophilus cultures or L. rhamnosus in a
double-blind trial design.
38. Potential pharmaceutical applications
(Intestinal Disorders):
• Clostridium difficile-Associated
Diarrhea:
• Clostridium difficile is a classical example
of the opportunistic proliferation of an
intestinal pathogen after breakdown of
colonization resistance due to antibiotic
administration.
• This microorganism is the major
identifiable cause of nosocomial diarrhea in
the United States, infecting 15 to 20 percent
of adult hospitalized patients.
Clostridium difficile
39. Potential pharmaceutical applications
(Intestinal Disorders):
• Traveler’s Diarrhea:
• Traveler’s diarrhea is a common health
complaint among travelers.
• Several probiotics have been examined for
their ability to prevent traveler’s diarrhea,
including Lactobacillus, Bifidobacterium, and
Streptococcus.
• In a recent study, Lactobacillus rhamnosus
GG was found to provide 49 percent
protection against traveler’s diarrhea.
Lactobacillus
rhamnosus GG
40. Potential pharmaceutical applications
(Intestinal Disorders):
• Infantile Diarrhea:
• Rotavirus is a very common cause of infantile
diarrhea, and is characterized by increased intestinal
permeability and a higher serum level of β-
lactoglobulin containing immune complexes.
• Investigators have demonstrated that the duration of
infantile diarrhea may be significantly shortened
(from 2.4 to 1.4 day) in infants receiving Lactobacillus
rhamnosus GG .
• Treatment with Lactobacillus rhamnosus GG was
associated with an enhancement of IgA-specific
antibody-secreting cells to rotavirus and of serum IgA
antibody level during convalescence.
41. Potential pharmaceutical applications
(Intestinal Disorders):
• Saavedra et al.have shown that
supplementing an infant formula with B.
bifidum and Streptococcus thermophilus
can reduce the incidence of acute diarrhea
and rotavirus shedding in infants admitted
to the hospital.
• Very recently, in a randomized, double-
blind, placebo-controlled trial,
administration of Lakcid L (Lactobacillus
rhamnosus GG ) to 87 children (age range:
2 months to 6 years) having infectious
diarrhea, the duration of rotaviral diarrhea
was markedly reduced.
42. Potential pharmaceutical applications
(Intestinal Disorders):
• HIV/AIDS-Associated Diarrhea:
• Diarrhea is a very serious consequence of
human immunodeficiency virus (HIV)
infection.
• Probiotics has been reported to treat 33 HIV
patients with chronic diarrhea.
• A randomized, double-blind, controlled trial
with 77 HIV-infected children (2 to 12 years),
divided into two groups: one receiving
probiotics (formula containing B. bifidum with
Streptococcus thermophilus) and the other, a
standard formula (control group).
Bifidobacterium
bifidum
43. Potential pharmaceutical applications
(Intestinal Disorders):
• There was an increase in the mean CD4*
count in the probiotics group and a small
decrease in the control group.
• This study showed that probiotics have
immunostimulatory properties and might
be helpful in the treatment of children
infected with HIV.
*CD4: glycoprotein found on the surface of the immune cells.
44. Potential pharmaceutical applications
(Intestinal Disorders):
• Enteral Feeding-Associated Diarrhea:
• Patients receiving nasogastric tube feeding
frequently develop diarrhea.
• The investigators postulate that the enteral
feeding causes changes in normal flora that
result in altered carbohydrate metabolism
and subsequent diarrhea.
• Two separate studies (both placebo
controlled and double blind) demonstrated a
significant reduction in diarrhea in these
patients when they were administered
probiotics.
45. Potential pharmaceutical applications
(Intestinal Disorders):
• Persistent or Chronic Diarrhea:
• Persistent diarrhea is diarrhea that starts
acutely but lasts for at least 2 weeks.
• A beneficial effect of feeding yogurt versus
milk was shown in children with persistent
diarrhea.
• Feeding fermented milk in children with
post-gastroenteritis syndrome eliminates
the disease in 4 days, and was even more
beneficial in patients with malnutrition.
46. Potential pharmaceutical applications
(Intestinal Disorders):
• Sucrase Isomaltase Deficiency:
• Sucrase isomaltase deficiency is an inherited
condition that leads to malabsorption of
sucrose.
• The resulting bacterial fermentation of sucrose
leads to an accumulation of hydrogen in the
colon, producing diarrhea, abdominal cramps,
and bloating.
• The investigators postulated that probiotics
supplying the missing isomaltase enzymes.
47. Potential pharmaceutical applications
(Intestinal Disorders):
• Lactase Deficiency:
• Lactose maldigestion occurs frequently
and is due to insufficient activity of
lactase in the human gut and causes
various degrees of abdominal
discomfort, such as cramps, bloating,
diarrhea, and nausea.
• Probiotic bacteria such as L.
acidophilus and bifidobacteria produce
β-d-galactosidase (bacterial lactase),
which autodigests lactose and
improves tolerance to lactose.
48. Potential pharmaceutical applications
(Intestinal Disorders):
• Other probiotics like L. acidophilus
may also be rich in lactase, but are
less efficient.
• It was observed that in the
lactase-deficient people, lactose is
absorbed much better from yogurt
than from milk probably due to
intraluminal digestion of lactose by
the lactase released from yogurt
microorganisms.
49. Potential pharmaceutical applications
(Intestinal Disorders):
• Inflammatory Bowel Disease (IBD):
• IBD is a collective term used to describe Crohn’s
disease (CD), ulcerative colitis (UC), and
nonspecific colitis.
• These diseases, although each with distinct
features, are characterized by inflammation of the
GIT that can lead to pain, diarrhea, and bleeding.
• Probiotics seem to represent an effective and
safe approach for the maintenance treatment of
patients with chronic CD.
50.
51. Potential pharmaceutical applications
(Intestinal Disorders):
• Helicobacter pylori Infection:
• Helicobacter pylori infection is a
major cause of chronic gastritis
and peptic ulcer and a risk factor
for gastric malignancies.
• Several reports suggested that
supplementation of anti-H. pylori
therapy with probiotics could be
effective in increasing the
eradication rates of H. pylori.
Helicobacter pylori
52. Potential pharmaceutical applications
(Intestinal Disorders):
• In vivo models demonstrate the
pretreatment with a probiotic can
markedly reduce an existing H. pylori
infection and thus can be used as a
prophylactic therapy for H. pylori
infections.
• Lactobacillus reuteri effectively
suppressed H. pylori infection in
humans and decreased the
occurrence of dyspeptic symptoms.
• Ingestion of L. acidophilus, L.
salivarius, or L. johnsonii reduced the
activity of H. pylori in the stomach. Lactobacillus
53. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Allergy:
• Allergy manifested in atopic diseases like
atopic eczema, allergic rhinitis, and asthma,
currently represents a chronic disorder
affecting 20 percent of the world population
especially in developed countries.
• It is the most common chronic disease of
childhood.
• Certain probiotics and microbial products have
been indicated to be potentially useful in
allergy prevention and therapy.
54. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Also, probiotics have been found to trigger
the innate immune system and thus help
protect against and treat allergies.
• A recent clinical study demonstrates a
highly significant reduction in the
frequency of atopic eczema in 2-year-old
children who as newborns were nursed
by their mothers and received a
Lactobacillus supplement.
55. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Gut microflora of allergic infants has an
atypical composition with reduced levels of
bifidobacteria, mainly B.adolescentis; and
increased levels of clostridia.Pro/prebiotics
have been shown to increase levels of
bifidobacterial.
• A study indicates usefulness of probiotic
therapy in prevention or long-term
reduction in allergy and also management
of atopic eczema and cow’s milk allergy in
infants.
56. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Immunity:
• The immune response to a particular
pathogen must induce an appropriate set
of effector functions that can eliminate
the disease agent or its toxic products
from the host.
• Probiotics exert immune-enhancing
effects by augmenting both nonspecific
and specific host immune responses.
57. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Probiotics stimulate lymphocytes to
produce cytokine INF-γ* and prompt
nonspecific phagocytic and lymphocytic
activity.
• Probiotics have also been found to
improve the defective immune function
via stimulating the cytokines IFN-γ, IL-
12, and IL-10*, all of which play a
putative suppressive effect on antigen-
specific immune responses.
IFN-Y , IL-12 , IL-10 : cytokines.
58. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Lactobacillus johnsonii and L. casei have
been reported to stimulate the production
IFN-γ and IL-10 secretion.
• Probiotics may have the capacity to
stimulate a cytokine response, by local
mononuclear cells or lymphocytes, and
that it depends in part on their capacity to
cross the gut epithelium before interacting
with the cells of local immune system.
59. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Oral administration of L. casei is reported
to improve the innate immune response
in mice and reduce skin inflammation due
to contact sensitivity in animals
sensitized to dinitrofluorobenzene.
• It has been reported very recently that
dietary synbiotic supplementation (L.
casei + dextran) elicited an enhanced
murine and human Natural Killer cell
activity.
60. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Urinary Tract Infections (UTI):
• Infections of the urethra, bladder, ureter,
and kidney affect nearly 3,000 million
women per year worldwide.
• They are due to microbial invasion or an
imbalance of the urinary tract
microflora.
• Nearly 50 bacterial strains are found to
cause UTIs.
61. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Bacterial and fungal infections of the
urinary tract are the most promising
field of application for probiotics
other than the intestine.
• Lactobacillus organisms that
predominate in the vagina of healthy
women spread from their rectum and
perineum and form a barrier to the
entry of uropathogens from vagina
into the bladder.
62. Potential pharmaceutical applications
(Nonintestinal Disorders):
• They are believed to protect the host
against infections by means of several
mechanisms including:
• (1) occupation of specific adhesion sites at
the epithelial surface of the urinary tract.
• (2) maintenance of a low pH and
production of antimicrobial substances
like acids, hydrogen peroxide, and
bacteriocins
• (3) degradation of polyamines.
• (4) the production of surfactants with
antiadhesive properties.
63. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Tomoda , reported that oral administration
of B. longum, in an open study, reduced
Candida infections in urethra by up to 70
percent.
• In vitro adhesion of C. albicans and
Staphylococcus aureus have been reported
to be reduced on epithelial cell lines of the
urinary tract by L. acidophilus, L.
rhamnosus.
• An open, randomized, clinical study showed
that local application of L. rhamnosus was
effective in controlling UTIs in up to 73
percent of the cases.
64. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Cholesterol reduction :
• Lots of researchers have proposed that
probiotics have cholesterol reduction
effects.
• The mechanism of this effect has not
been explained definitely.
• There are two hypotheses trying to
explain the mechanism:
• -One of them is that bacteria may bind or
incorporate cholesterol directly into the
cell membrane.
65. Potential pharmaceutical applications
(Nonintestinal Disorders):
• -The other one is, bile salt hydrolysis
enzymes deconjugate the bile salts
which are more likely to be exerted
resulting in increased cholesterol
breakdown.
• A study on the reduction of cholesterol
showed that Lactobacillus reuteri CRL
1098 decreased total cholesterol by
38% when it was given to mice for 7
days in the rate of 104 cells/day.
66. Potential pharmaceutical applications
(Nonintestinal Disorders):
• Carcinogenesis:
• Colorectal cancer is the fourth most common cause
of cancer morbidity and mortality worldwide.
• Colon cancer occurs due to somatic mutations in
colon cells occurring during the lifetime of an
individual.
• Genotoxic carcinogens including heterocyclic
aromatic amines, which are formed during cooking
of meat, are a potential risk factor of colon cancer
in high meat consumers.
• These enzymes include glycosidase, β-
glucuronidase, azoreductase, and nitroreductase.
67. Potential pharmaceutical applications
(Nonintestinal Disorders):
• At present, direct experimental evidence is
lacking for suppression of cancer in humans
by probiotic bacteria, but a good deal of
indirect evidence has been described.
• Some suggested mechanisms:
• (1) inhibition of carcinogens and/or
procarcinogens
• (2) inhibition of bacteria that convert
procarcinogens to carcinogens
68. Potential pharmaceutical applications
(Nonintestinal Disorders):
• (3) activation of host’s immune system
• (4) reduction of intestinal pH to reduce
microbial activity
• (5) alteration of colonic motility and transit
time.
• There has been evidence that some probiotics
produce butyric acid and this molecule can
influence the rate of apoptosis in enterocytes.
69. Probiotics in infant nutrition:
• Human milk is the ideal nutrition for term
infants because it provides all necessary
nutrients for rapid growth and postnatal
development.
• The positive effects of breastfeeding are
multifactorial. One of the physiologic
aspects of the effects of breastfeeding is
the establishment of a specific intestinal
microbiota.
70. Probiotics in infant nutrition:
• There is increasing evidence that the
composition of the intestinal microbiota
plays a key role in the postnatal
development of the immune system
• Addition of probiotic bacteria to infant
formula has shown promising benefits in
treatment and prevention of allergy,
treatment and prevention of acute
infectious diarrhea.
71. Probiotics for elderly:
• Aging affects the gastrointestinal (GI) tract
in many ways. The aging-associated
physiological changes influence the GI tract
microbiota both directly and indirectly.
• First, physiological changes affecting a
person’s eating behavior include increased
taste and smell thresholds, decreased
muscle strength for chewing, and loss of
teeth, which all can lead to a very selective
consumption of foods and consequently to
an altered nutritional status or even to
malnutrition.
72. Probiotics for elderly:
• The particular challenges related to the
probiotic research include the right selection
criteria for probiotic strains for elderly
individuals.
• specific probiotics can provide measurable
and clinically relevant benefits to elderly
people in counteracting the age-related
changes in gut microbiota, enhancing
immunity, and promoting intestinal health.
73. Probiotics in animal nutrition:
• The beneficial modes of action
include: regulation of intestinal
microbial homeostasis,
stabilization of the
gastrointestinal barrier function,
expression of bacteriocins,
enzymatic activity inducing
absorption and nutrition,
immunomodulatory effects,
inhibition of procarcinogenic
enzymes and interference with
the ability of pathogens to
colonize and infect the mucosa .
74. Probiotics in animal nutrition:
• It has been recognized that
functionality of multistrain and
multispecies probiotics could be
more effective than that of
monostrain probiotics.
• The advantages of administering
multistrain and multispecies
probiotics include the enhanced
capability of colonizing the
gastrointestinal tract and to
combine the different
mechanisms of action of each
strain in a synergistic way.
75. Safety of probiotics :
• The correct identification of probiotic strain is
crucial to evaluate the health benefits and the
safety of probiotics and to avoid the inclusion of
potentially pathogenic microorganisms in
commercial products .
• In vitro assessment of probiotics:
• Based on the intrinsic properties of the strains ,
it should always precede the use of potential
probiotics strains in animals and humans.
• Probiotics microorganisms have to be
systematically screened for antibiotics
resistance susceptibility in order to avoid the
transfer of antibiotic resistance genes .
76. Safety of probiotics :
• The presence of virulence factors has been used to
demonstrate the safety of probiotics species.
• Testing the ability to aggregate human platelets.
• Resistance to host defense mechanisms.
• Animal models can be used to test the efficacy and
safety of probiotics , it must be conducted
humanely and only when similar results cannot be
obtained by alternative methods.
• Testing should be conducted in animals with lowest
degree of neurophysiologic sensitivity, and the
lowest number of animals should be employed.
• The animal model must be free from unwanted
microbial agents.
77. Safety of probiotics :
• Probiotic strains manufacturing criteria:
• Ease in maintaining in storage without loss of
viability.
• Ability to revitalize and grow quickly to the
maximum concentration in a simple and cheap
fermentation medium.
• Ability to grow and survive in microaerophilic or
aerobic conditions.
• Ability to withstand physical handling without
significant loss of viability.
• Ability to survive in the food matrices and during
processing.
78. References :
• Charalampopoulos, D., & Rastall, R. A. (Eds.). (2009). Prebiotics and probiotics science and technology (Vol. 1).
Springer Science & Business Media.
• Cho, S. S., & Finocchiaro, T. (Eds.). (2009). Handbook of prebiotics and probiotics ingredients: health benefits
and food applications. CRC press.
• Malago, J. J., Koninkx, J. F. J. G., & Marinsek-Logar, R. (2014). Probiotic bacteria and enteric infections.
Springer.
• Otles, S. (Ed.). (2013). Probiotics and prebiotics in food, nutrition and health. CRC Press.
• e Silva, J. P. S., & Freitas, A. C. (Eds.). (2014). Probiotic bacteria: fundamentals, therapy, and technological
aspects. Crc Press.
• Tamime, A. Y., Thomas, L. V., & Wiley, J. (Eds.). (2005). Probiotic dairy products. Blackwell Pub..
• Lee, Y. K., & Salminen, S. (2009). Handbook of probiotics and prebiotics. John Wiley & Sons.