Health Benefits of Probiotics
Course
Functional Foods and Nutraceuticals
Week
Two
Module
Six
Title
Health Benefits of Probiotics
Sub theme
Health Benefits of Probiotics, Including Mechanism of Action
Principal Investigator
Dr Rekha Sharma, Associate Professor, UGC- Human Resource
Development Centre, Rashtrasant Tukadoji Maharaj Nagpur
University, Nagpur
Content Writer
Dr Preeti Dharmik, Assistant Professor, UGC- Human Resource
Development Centre, Rashtrasant Tukadoji Maharaj Nagpur
University, Nagpur
Content Reviewer
Dr Sabiha Vali, Former Professor and Head, Post Graduate
Teaching Department of Home Science, Rashtrasant Tukadoji
Maharaj Nagpur University, Nagpur
Content Reviewer
Dr Pratima Shastri, Former Professor and Head, Department of
Food
Technology,
Laxminaryan
Institute
of
Technology,
Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur
Objectives:
After studying this module, the learners shall be able to:
·
describe the basic mechanisms of Probiotic function
·
explain various health benefits of Probiotics
Introduction:
·
As we all know, Probiotics possess important functional attributes that could
fulfil most of our basic nutritional and clinical supplementation requirements.
·
These microbes have shown positive responses to clinical treatment against
several diseases and disorders.
·
Moreover, the contribution of probiotics in preventing and treatment of
diabetes, obesity, cancer and diseases related to pathogenic microbes is an
exciting and rapidly advancing research arena.
UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
·
Probiotics have demonstrated significant potential as therapeutic options for a
variety of diseases, but the mechanisms responsible for these effects have
not been fully elucidated yet.
·
Hence, in this module we will focus on several important mechanisms
underlying the antagonistic effects of probiotics on various microorganisms.
Mechanisms of Probiotic Function
o Enhancement of the Epithelial Barrier
o Increased adhesion to intestinal mucosa
o Inhibition of pathogen adhesion
o Competitive exclusion of pathogenic microorganisms
o Production of antimicrobial substances
o Modulation of the immune system.
All these mechanisms are depicted in Figure 1 and Table 1:
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
Table 1: Various mechanisms of probiotics action on human intestine cells.
Mode
Process
Mechanism
Examples
Barrier Function
Decreased
Decreased TNF-α
Lactobacillus
apoptosis of
production
rhamnosus GG
Increasing mucin
Increased
Lactobacillus sp
production
expression of MUC
epithelial cells
2
Host cell
Defensins (hBD
Increased up
E coli strain DSM
Antimicrobial
protein)
regulation of
17252S2
Peptides
Defensin
Cathelcidins
By butyrate
production
Probiotic
Lowering the
By secretion of
Most of the
Antimicrobial
luminal pH
SCFA’s
probiotics bacteria
Factors
Bacteriocin
By Gram positive
production
probiotics
Microcin production By Gram negative
probiotics
Epithelial
By competing with
Directly or indirectly
Adherence
pathogens
by producing
protein that block
adherence
Immune
Blocking pro
By attenuating IL-8
Salmonella
Modulation
Inflammatory
secretion or
tyhimurium VSL#3
molecules
blocking the
probiotics
degradation of the
counter-regulatory
factor IκB
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
Increasing mucosal
Increasing IgA
immunity
Production
Interference with
Blocks the
By secreting
Quorum Sensing
communication
molecules which
Signaling
between
blocks quorum
pathogenic
sensing signaling
L. casei
L. acidophilus
bacteria
Abbreviations: TNF-α: Tumor necrosis factor alpha; MUC 2: Mucin 2, hBD:
Hemoglobin subunit delta; SCFA: Short chain fatty acids; IL-8: Interleukin 8; and IκB:
Inhibitor of kappa B.
a. Barrier function
As we all know The intestinal tract is a diverse microenvironment where more than
500 species of bacteria thrive. A single layer of epithelium is all that separates these
commensal microorganisms and pathogens from the underlying immune cells, and
thus epithelial barrier function is a key component.
The epithelial barrier consists of a dense mucous layer containing secretory IgA and
antimicrobial peptides as well as dynamic junctional complexes that regulate
permeability between cells. Probiotics are live microorganisms that confer benefit to
the host and that have been suggested to prevent diseases including antibioticassociated
diarrhea,
irritable
bowel
syndrome,
and
inflammatory
bowel
disease. Probiotics are capable of influencing many of the components of epithelial
barrier function either by decreasing apoptosis of intestinal cells or increased mucin
production. Lactobacillus species have been shown to increase mucin expression in
vitro in human intestinal epithelial cells, thus blocking pathogenic E. coli invasion and
adherence.
b. Production of antimicrobial substances
Probiotics either by inducing host cells to produce peptides or by directly releasing
peptides interfere with pathogens, and prevent epithelial invasion. Defensins (hBD
protein) and cathelicidins are the antimicrobial peptides expressed constitutively by
the intestinal epithelial cells and display antimicrobial activity against a wide variety
of bacteria, fungi and some viruses. Probiotics have been shown to suppress
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
pathogen growth through the release of a variety of antimicrobial factors like
defensins, bacteriocins, hydrogen peroxide, nitric oxide, and short chain fatty acids
(SCFA), such as lactic and acetic acids. Microcins (produced by gram negative
bacteria), on the other hand, can target the inner membrane, enzymes that are
involved in DNA or RNA structure synthesis, or protein synthesis enzymes.
Similarly, the production of H2O2 by these bacterial groups causes the oxidation of
sulfhydryl groups, resulting in the denaturation of several enzymes results in the
peroxidation of membrane lipids, thus, increasing membrane permeability of the
pathogenic microorganism and consequently, cell death. Some of these compounds
may act by lowering pH by organic acids like lactic and acetic acids.
c. Competition for adherence
Competition of commensal and probiotic bacteria with pathogens for adhesion and
colonization is one of the important protective mechanisms of gastrointestinal
tract. The epithelial cells of gastrointestinal tract (GIT) are protected from pathogenic
bacteria by a number of mechanisms. One of them is a reduction in pathogenic
infections through competition of microbiota for adhesion sites with microbial
pathogens and production of components with antimicrobial activity. To cause
infection, pathogenic bacteria, after penetrating intestinal mucus, must adhere to
enterocytes. The initial step of adhesion in the case of Salmonella species is
mediated by bacterial fimbriae which recognize certain receptors on eukaryotic cells.
Several studies indicate that lactic acid bacteria (LAB) could prevent the attachment
of pathogens, in this way reducing colonization, and prevent infection
Similarly S. boulardii secretes a heat-labile factor which has shown to be responsible
for the decreased bacterial adherence. Another mechanism by which probiotics exert
anti-pathogenic activity is by competing for available nutrients and growth.
d. Immune modulation
Probiotics are non-pathogenic live microorganism that can provide a diverse health
benefits on the host when consumed in adequate amounts. Recently, many reports
suggest that certain probiotic strains or multi strain mixture have potent immunemodulatory activity in diverse disorders including allergic asthma, atopic dermatitis
and rheumatoid arthritis. Probiotics have been found to enhance the innate immunity
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
and modulate pathogen-induced inflammation via toll-like receptor-regulated
signaling pathways. L. casei have been shown to augment total and pathogenspecific secretory IgA levels upon infection in mice by stimulating B cell. Specific
antibodies against L. casei were not produced, indicating the non-responsiveness of
the gut immune system to this beneficial bacterium. L. casei down-regulated the
transcription of a number of genes encoding pro-inflammatory effectors such as
cytokines and chemokines and adherence molecules induced by invasive S. flexneri.
In addition to this It is well known that probiotic bacteria can exert an immunemodulatory effect. These bacteria have the ability to interact with epithelial and
dendritic cells (DCs) and with monocytes/macrophages and lymphocytes.
e. Interference with quorum sensing signaling
Bacteria communicate with each other as well as with their surrounding environment
through chemical signalling molecules called auto-inducers. This phenomenon is
called quorum sensing. The use of this cell-to-cell signalling mechanism facilitates
the regulation of important traits of enteric microbes that allow them to successfully
colonize and/or start infection in their host. Medellin-Pena et al. demonstrated that
Lactobacillus acidophilus secretes a molecule that inhibits the quorum sensing
signalling or directly interact with bacterial transcription of E. coli O157 gene,
involved in colonization and thus, bacterial toxicity is opposed.
So friends so far we have finished all the basic mechanisms of action of
probiotics
We will now discuss these mechanisms in detail with respect to following activities:
•
Anti-pathogenic activity of Probiotics
•
Urogenital Health Care
•
Anti-diabetic activity of Probiotics
•
Anti-inflammatory activity of Probiotics
•
Anti cancer activity of Probiotics
•
Anti Allergic activity of Probiotics
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
•
Angiogenic activity of Probiotics
•
Effect of Probiotics on brain and CNS
1. Anti pathogenic activity of probiotics:
•
Anti-pathogenic activity is regarded as one of the most beneficial effects of
probiotics.
•
There has been considerable research on the anti-pathogenic activity of
probiotics or a probiotic mixture.
Scientist found that there are number of mode of actions of probiotics through which
they confer anti pathogenic activity such as:
·
Production of short-chain fatty acids (SCFAs), such as acetic, propionic,
butyric and lactic acids: SCFAs help to maintain an appropriate pH in the
colonic lumen, which is imperative in the expression of numerous bacterial
enzymes and in metabolism of foreign compounds and carcinogens in the gut.
·
Apart from short chain fatty acids probiotics also produce wide variety of antipathogenic compounds, like bacteriocins, ethanol, organic acids, diacetyl,
acetaldehydes, hydrogen peroxide (H2O2) and peptides are produced by
many probiotics.
·
Among these compounds, peptides and bacteriocins, in particular are mostly
involved in increasing the membrane permeability of the target cells, which
leads to cell death.
·
Similarly, the production of H2O2 by these bacterial groups causes the
oxidation of sulfhydryl groups, resulting in the denaturation of several
enzymes results in the peroxidation of membrane lipids, thus, increasing
membrane permeability of the pathogenic microorganism and consequently,
cell death.
·
Some of these compounds may act by lowering pH by organic acids like lactic
and acetic acids.
2. Urogenital Health Care
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
·
According to the Centers for Disease Control and Prevention (CDCP), more
than one billion women around the world suffer from non-sexually transmitted
urogenital infections, such as bacterial vaginosis (BV), urinary tract infection
(UTI) and several other yeast infections.
·
The two most commonly documented bacterial STDs in some developed
countries are gonorrhea and Chlamydia, which are caused by Neisseria
gonorrhoeae and Chlamydia trachomatis, respectively.
·
It is well-known that there is an association between abnormal vaginal
microbial flora and an increased incidence of urinary tract infection (UTI).
·
There are about 50 different species inhabiting the vagina, like Lactobacillus
species, Lactobacillus brevis, Lactobacillus casei, Lactobacillus vaginalis,
Lactobacillus delbrueckii, Lactobacillus salivarius, Lactobacillus reuteri, and
Lactobacillus rhamnosus that are regarded as the main regulators of the
vaginal micro-environment.
·
Imbalance in the microbial composition greatly influences the health of the
vaginal microenvironment, potentially leading to compromised state of
bacterial vaginosis (BV) and UTI. These compromised states can be
reassured
by
balancing
the
number
of
Lactobacillus
sp.
via
the
supplementation of probiotics.
3. Anti-diabetic activity of Probiotics:
·
Probiotics may be considered as a biotherapeutic agent for diabetes.
Several nutraceuticals and probiotic preparations have been studied for
anti-diabetic activity in different laboratories.
·
Due to the following properties probiotics can be considered as an
alternative therapeutic regimen for diabetes:
o Antidiabetic effect
o Antioxidant properties
o Antihypercholesterolemic and/or antiatherogenic properties
o
Hypotensive effect
o Immunomodulatory effect
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
·
Researchers
have
demonstrated
that
Lactobacillus
possesses
antihyperglycemic and insulin releasing activity and insulin mimic and
immunomodulatory effect.
It also prevents destruction of β-cells by
autoimmunity in children genetic risk of type 1 diabetes.
·
Patients with type 2 diabetes have significantly reduced numbers of
Lactobacillus and other probiotics which positively correlates with plasma
glucose concentration. Possible reason for alteration of gut microbiota in
diabetes may be non availability of fermentable sugars and carbohydrates
which are common substrates hence regular replenishment can be helpful.
4. Anti-inflammatory activity of Probiotics:
·
Inflammatory Bowl Disasese (IBD) is being associated with impaired
production of SCFAs, particularly, acetate, butyrate, and propionate.
Moreover, these SCFAs have been known to play a key role in
maintaining colonic homeostasis.
·
probiotics also possess anti-inflammatory effects and improve the
propulsive colonic function.
·
Therefore, it is reasonable to consider that supplementation with
indigestible carbohydrates and fiber (prebiotic) alone, or in combination
with probiotics to increase the production of SCFAs could be useful
therapeutic approaches.
5. Anti cancer activity of Probiotics:
·
In vitro studies have demonstrated that probiotic strains, Lactobacillus
fermentum NCIMB-5221 and -8829, are highly potent in suppressing
colorectal cancer cells and promoting normal epithelial colon cell
growth through the production of SCFAs (ferulic acid).
·
Again two different probiotic strains L. acidophilus LA102 and L. casei
LC232 have also been found to show pronounced cytotoxic activities,
with in vitro anti-proliferative activity against two colorectal cancer cell
lines (Caco-2 and HRT-18).
6. Anti Allergic activity of Probiotics:
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
·
In vitro studies of certain probiotics, such as Lactobacillus plantarum
L67, have shown the potential to prevent allergy-associated disorders
with the production of interleukin-12 and interferon-gamma in their
host.
7. Angiogenic activity of Probiotics:
·
Angiogenesis has been an important phenomenon and is necessary for
wound healing process. The angiogenic process consists of series of
cellular events by which new vessels arise from pre-existing ones by
promoting recruitment of inflammatory cells and producing cytokines,
matrix-degrading enzymes, and chemokines.
·
Deregulated angiogenesis has a prominent impact on major human
diseases, such as cancer, diabetic retinopathy, and IBD including CD
and UC.
·
Non-pathogenic probiotic yeast, Saccharomyces boulardii, has been
reported to protect against intestinal injury and inflammation.
·
The potential mechanisms of probiotics in angiogenesis process may
include alteration of inflammatory cytokine profiles, down regulation of
pro-inflammatory cascades or induction of regulatory mechanisms in a
strain-specific manner, epithelial barrier function enhancement, visceral
hypersensitivity reduction, spinal afferent traffic, and stress response.
·
Probiotics plays a significant role in inducing intestinal angiogenesis by
vascular endothelial growth factor receptor (VEGFR) signaling that, in
turn, regulates acute and chronic inflammation in intestinal mucosal
tissue caused by the progression of inflammatory bowel disease (IBD)
8. Effect of Probiotics on brain and CNS:
·
The colonization of microbiota in the GIT is well-associated with both
GIT and gastrointestinal diseases.
·
The
“microbiota-gut-brain
axis”
is
an
interactive,
bi-directional
communication established by the exchange of regulatory signals
between the GIT and CNS.
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
·
The effect of probiotics on the CNS has been mainly studied in clinical
trials, where it has been evident that gut microbiota influence human
brain development function.
·
In children with autism spectrum disorder, a daily dose of L. plantarum
WCFS1 day) led to an improvement in their school records and attitude
towards food.
·
A decrease in anxiety symptoms by administration of L. casei strain
Shirota to patients suffering from chronic fatigue syndrome is observed.
However, despite an increase in the Lactobacillus and Bifidobacteria
levels, the bowel functions were not studied. Hence, it is feasible that
the reduced anxiety was due to improved bowel function.
·
It has been observed that many gut bacteria synthesize to neuroactive
compounds similar to those produced in the host brain. Human
intestinally derived strains of L.brevis DPC6108 and Bifidobacterium
dentium were reported to produce large amounts of g-aminobutyric
acid, a brain neurotransmitter that helps humans to suppress anxiety
and depression.
·
Oral intake of L. acidophilus has been shown to assist people to
regulate their mood towards rewards and addictive behaviour.
9. Anti-obesity activity of probiotics
Abnormal or excessive fat (obesity) accumulation that directly impairs
health is linked to an increase in energy availability, sedentariness and a
greater control of ambient temperature, leading to an imbalance in energy
intake and expenditure. Probiotic strains, Lactobacillus gasseri BNR17 have
shown properties of inhibiting the increase in adipocyte tissue that are the
main source of leptin and adiponectin and thereby, limiting leptin secretion.
Other probiotic microbes such as L. casei, Lactobacillus acidophilus and
Bifidobacterium longum have also been reported to have hypocholesterolemic
effects.
Apart from previously explained effects, Probiotics are also used in treatment and
prevention of various medical conditions like
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
a. Antibiotic-associated diarrhea (AAD):
The incidence of antibiotic-
associated diarrhea (AAD) ranges between 5% and 30%. The risk is greatest
with aminopenicillin therapies (Ampicillin or Amoxicillin), aminopenicillin
combined with clavulanic acid, cephalosporins, and clindamycin. The major
changes in the microbiota of the gut with antibiotics are decrease in total
number and species diversity of Bacteroidesand Bifiobacteriaassociated with
decreased amylolytic activity with increase in facultative anaerobes such as
Fusobacteria, Clostridia, and Eubacteria species. Decreased short chain fatty
acid production and increased proteolytic activity was also noted in elderly
patients treated with antibiotics. Several clinical trials have been conducted
using Saccharomyces boulardiifor the prevention of AAD. All but one
concluded that S. boulardiiwas an effective agent for prevention of AAD.
b. Probiotics and Clostridium difficile Infections:
spore-forming,
anaerobic,
Gram-positive
Clostridium dfficileis a
bacterium
that
causes
gastrointestinal infection with diarrhea and colitis. Probiotics have been
studied in prevention, and treatment of Clostridium difficile infections (CDI)
and recurrent CDI. The probiotics like Saccharomyces boulardii,Lactobacillus
spp and Bifidiobacteriumspp has been increase in the practice of using
probiotics along with vancomycin or metronidazole for recurrent CDI.
c. Probiotics and Helicobacter pylori Infections: Helicobacter pylori, a small
curved to spiral rod shaped bacterium, is strongly associated with duodenal
peptic ulceration and it is the main etiologic agent of chronic gastritis and
gastric cancer and other gastric malignancies. Today the therapy to eradicate
this bacterium is based on a combination of antibiotics and proton pump
inhibitors. Probiotics seem to have a direct antimicrobial effect. Probiotics
significantly improved symptoms, including taste disturbance and diarrhea.
d. Probiotics and Acute Pancreatitis: Probiotics have been shown to be
effective in preventing complications in experimental acute pancreatitis by
reducing bacterial translocation.
e. Probiotics and Necrotizing Enterocolitis (NEC): Necrotizing enterocolitis is
a potentially devastating disease, characterized by severe intestinal
inflammation and necrosis, which occurs primarily in preterm infants. Reviews
showed that the use of probiotics reduces the occurrence of NEC and death
in premature infants born less than 1500 grams.
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
f. Probiotics and Multi-Organ Dysfunction Syndrome (MODS): Impaired
intestinal barrier function has been assumed to play a role in the development
of sepsis and multiple organ failure (MOF) in patients with decreased gut
perfusion following major surgery, trauma or shock. Probiotics can decrease
the sign s and symptoms of this disease.
g. Probiotics and Ventilator-associated pneumonia (VAP): Ventilatorassociated pneumonia (VAP), defined as pneumonia occurring more than 48
hours after endotracheal intubation, is a leading hospital-acquired infection.
Lactobacillus casei and rhamnosusstrain demonstrated a decrease in VAP
incidence.
Conclusion:
Hence in this module we have seen anti-inflammatory activity, anti cancer activity,
anti allergic activity, angiogenic activity of probiotics, effect of probiotics on brain and
CNS and antiobesity effect of probiotics. Apart from that we have also seen in brief
probiotics which are also used in treatment and prevention of various medical
conditions likeAntibiotic-associated diarrhea (AAD), Clostridium difficile Infections,
Helicobacter pylori Infections, Acute Pancreatitis, Necrotizing Enterocolitis (NEC),
Multi-Organ Dysfunction Syndrome (MODS) and Ventilator-associated pneumonia
(VAP).
References:
1. Rout George Kerry , Jayanta Kumar Patra , Sushanto Gouda Yooheon Park ,
Han-Seung Shin , Gitishree Das., (2018) Benefaction of probiotics for human
health: A review, Journal of Food and Drug Analysis 26, 927-939.
2. Miriam Bermudez- Brito Julio Plaz a - Díaz Sergio Muñoz- Quez ada, Carolina
Gómez- Llorente Angel Gil., (2012)., Probiotic mechanisms of action., Ann
Nutr Metab 2012;61:160–174.
3. Gogineni VK, Morrow LE, Malesker MA (2013) Probiotics: Mechanisms of
Action and Clinical Applications. J Prob Health 1: 101. doi: 10.4172/23298901.1000101
4. Slavin J. (2013) Fiber and prebiotics: mechanisms and health benefits.
Nutrients;5:1417e35.
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UGC PG MOOC on Functional Foods and Nutraceuticals
Module 6: Health Benefits of Probiotics including Mechanism of Action
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3b112a7e65524518
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).pdf
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