1.

INTRODUCTION
Probiotics can be defined as live microorganism having several health benefits when consumed.
According to WHO's 2001 "Probiotics are live micro organism which when administered in
adequate amount confer health benefit on the host".
Probiotic term comes from greek word Pro Bios which means for life.They are actually
friendly bacteria that offer many benefits to our body. They either already present in body or
provided in supplement form.
Lactic acid bacteria are most commonly used probiotic (for e.g. L.casei, L.rhamnosus etc).These
kind of lactobacillus are found in yogurt.Other bacteria that are used as probiotics are non lactic
acid bacteri and non pathogenic yeast.

fig. 1-a)Lactic acid bacteria b)probiotic
2.HISTORY
Discovery of certain bacteria as probiotics was introduced by russian scientist and nobel prize winner,
Elie metchnikoff of the pasteur institute in 1900s. In 1907,Metchnikoff observrd that certain inhabitants
of the bulgarian population have longer life span than other.This fascinated him. Later he discovered
that villagers living in the cancasus mountains were drinking a fermented yoghurt drink on a daily
basis.He found that a probiotic called Lactobacillus bulgaris improved their health and may have the
longevity of their lives.
He named it bulgarian bacillus which is LAB. He suggested it is possible to modify gut flora by replacing
harmful microbes with useful microbes.
Bifidobacteria first discovered by Henry tissier (working in pasteur institute) from a breast fed infant.He
observed the clinical benefits from treating diarrhea in infants with bifido bacteria.
German professor Alfred nissle isolated on the E.coli strain from the feaces of a soldier who was
not affected from acute gastrointestinal infections shigellosis (during the outbreak of shigellosis
in 1917). Probiotics term was 1st coined by werner kollath in 1953.

2.Health benefit of probitics.
Live microorganisms having therapeutic benefit for the host are referred as Probiotics.Probiotics are
usually recommended to strengthen immune system of host and for maintaining gut flora.
Usually ,they are harmless but in some rare cases.(e.g.in immunocompromised patients),it can cause
infection.
Probiotics are known for curing many diseases like:-
I. Inflammatory diseases and bowel syndrome
II. Cancer
III. Constipation
IV. Mucosal immunity
V. Allergy
VI. Cardiovascular diseases
VII. Urogenital tract disorders
VIII. Bacterial vaginosis
IX. Yeast vaginitis
X. UTI

Different probiotics and their health benefit.:-
sTable 1: Few examples of probiotics.
Sr.No Genus Species Strains
1 Lactobacillus L.bulgarius reference symbiosis 585
L.casei YIT 9018, ATCC53103
L.rhamnosus GG, ATCC53103
L.johnsonii la-1
L.plantarum Lp299v, wcfs1
2 Streptococcus S.thermophilus S85
3 Bifidobacterium
DN-
B.animalis 173010
B.breve NCIMB8807
B.longum NCC2705, DJOIOA

a. Bifidobacterium lactis- regulates digestion system
b. bifidobacterium infatis- promotes digestive health
c. lactobacillus rhamnosus- restore and maintain normal gastrointestinal flora; prevent/ treat oral
candidiasis and diarrhea due to antibiotics; managment of herps stomatitis.
d. lactobacillus acidophilus-promotes and maintains a healthy and balanced digestive system.
e. lactobacillus GG- improves digestion and digestive health,prevent gas and bloating,support
immune system and well being and reduce travel associate digestive complaints.
f. lactobacillus bulgaricus/ L.casei- strenghen body's defenses .
g. saccharomyces boulardii- protect against digestive imbalance due to antibiotic travels,stress,
diet.
h. lactobacillus helveticus/bifidobacterium longum- balances gut flora to maintain
health,decrease stress,related digestive symptoms.

Although mechanism of inflammation is not well documented.In my review I am focusing on
different mechanism involved in controlling inflammation by probiotics.
3.Inflammation:- It is a protective reaction of body's immune response which aim to remove harmful
foreign substance.It actually aim to clear up the infection by clearing damage cells,pathogens etc.
Inflammation is usually induced by chemical mediators induced by damage host cells.For example-
cytokines and other mediators. Cardigal signs of inflammation are
heat(calor),redness(rubar),swelling(tumor),pain(dolor),loss of function.



Fig2 :-Toes inflamed by chilblains.
4.Inflammation mechanism:-
Recognition of infection:-
Toll like receptors (TLRs) recognize infection. TLRs detect pathogen associated molecular
pattern like LPS or peptide which is important for their survival and bind with it.After ligand
binding and conformational change of TLRs ,it recruit adaptor protein My D88 and undergo My
D88 dependent pathway.

My D88 dependent pathway:
My D88 recruit IRAK 1, IRAK 2 which phosphorylate and activate the protein TRAF6.This traf6
degrade itself as well as protein TAK1 for the binding to IkkB. This TAK1 further phosphorylates
IkkB which when phosphorylate IkB,cause its degradation from NFkB and allowing NFkB to
transcription into the cell nucleus and activate transcription and inflammatory cytokines.

Release of proinflammatory cytokines:
Transcription and translation of genes induce the expression of proinflammatory cytokines such
as IL Beta,IL R,TNF-alpha and other.
In conjuction with chemokines,these proteins facilitate the recruitment of effector cells such as
monocyte and neutrophils to the site of infection by chemotaxis.
Mast cells and macrophages promotes this migration by releasing histamine, leukotrines and
prostaglandins.
Neutrophils secrete ROS and various proteinases which is descructive to both pathogen and
host which ultimately leads to inflammation.

5)Stages of inflammation
Acute inflammation- It is a complex process of bodys immune response that protect and heal
the body following infection.It actually aims to improve blood flow to the injured partby local
dilation of blood vessel as well as by increasing vessel permeability.Signaling molecules and
different chemoattractants are released by mast cells,platelets, and other resident cells at the
site of infection that recruit leukocytes (e.g neutrophils)to the injured area.Neutrophils is the
first leukocyte which appear at the affected area.Thsese cells release non-specific toxins such as
superoxide radicals, hypochlorite and hydroxyl radicals which phagocytose and kill invading
microorganisms.These ROS kill pathogen as well as also damage adjacent cells.Neutrophils
release cytokines, including interleukin-1,interleukin-6 and tumor necrosis factor-alpha and
others which in turn induce liver to synthesize various acute phase reactant protein as well as
systematic inflammatory response(e.g.fever).

Chronic inflammation-if immune response against injury persists for longer period,inflammation can
last days,months and even years which lead to chronic inflammation.Monocyteand macrophages are
primary mediators of chronic inflammation.when monocyte leave the blood stream and after entering
tissue it mature into macrophages.These macrophages phagocytose microorganisms,older cells and
foreign cells.Different chemicals mediators like IL-1,TNF-alpha etc are released by macrophages that
sustain pro-inflammatory response which is accompanied by lymphocytes at later stages that invade the
affected or damage tissues.Further on,virus infected cells are killed by T lymphocytes whereas B
lymphocytes produce antibodies that target specifically invading microorganisms responsible for
destruction.ROS and protease(release by macrophages and other leukocytes) not only destroy source of
inflammation but also harm bodys own healthy tissues.Infact,tissue damage is sure sign of chronic
inflammation.In some cases, body is unable to repair tissue damage and the inflammatory process
continues.
Chronic inflammation is not a bodys normal process and does not benefit the body and in fact it is
responsible for number of disease. Tissue damage that occurs during the inflammatory response must
be actively cured otherwise it can lead to many severe diseases.
Table 2:comparison of acute and chronic inflammation.
Acute Chronic
Causative agents harmful bacteria or injury to
tissue
non degradable pathogens
that cause persistent inflammation,
infection with some
types of viruses,persistent
foreign bodies
Major cells involved mainly neutrophils,basophils
(in the inflammatory),and
eosinophils(response to
parasites and worms),and
mononuclear cells
(macrophages,
monocytes)

macrophages,lymphocytes,
plasma
and fibroblasts.

Primary mediators eicosanoids, vasoactive
amines

reactive oxygen species,
hydrolytic enzymes,
IFN-gamma and other cytokines,growth
factors.

Duration the inflammation either gets
better,develops into an
abscess
or become a chronic
inflammation.
the destruction of tissue,
thickening
and scarring of
connective tissue(fibrosis),
death of cells or tissues
(necrosis).
Outcomes short lived,only a few days from several months to
years

Many different probiotics are recommended for curing chronic inflammation. for example-lactobacillus
sp., l.acidophiles,etc.

6) PROBIOTICS IN CONTROLLING INFLAMMATION:-

Lactobacillus rhamnosus gg- decreases TNF alpha induced IL-8 production by caco-2 cells via
interference with NFk b activation.
Lactobacillus sp.- increase expression of MUC 2.
L.acidophiles- by secreting molecules which blocks quorum sensing signalling.
Bacillus subtilis-secrete quorum sensing molecules which induce expression of cytoprotectant heat
shock protein. (heat shock proteins expression is increased when are exposed to elevated tempratures
or other stress.