1.

INTRODUCTION
Probiotics can be defined as live microorganism having several health benefits when
consumed. According to WHOs 2001 "Probiotics are live micro organism which when
administered in adeuate amount confer health benefit on the host". Probiotic term
comes from !ree" word #Pro $ios% which means for life. &he' are actuall' friendl'
bacteria that offer man' benefits to our bod'. &he' either alread' (resent in bod' or
(rovided in su((lement form.
)actic acid bacteria are most commonl' used (robiotic *for e.g. ).casei+ ).rhamnosus
etc,.&hese "ind of lactobacillus is found in 'ogurt. Other bacteria that are used as
(robiotics are non lactic acid bacteria and non (athogenic 'east.
-ig. 1.a, lactic acid bacteria b, probiotic
2. HISTORY
/iscover' of certain bacteria as (robiotics was introduced b' 0ussian scientist and
1obel Pri2e winner+ 3l' 4etchni"off of the Pasteur institute in 1500s. 6n 1507+
4etchni"off observed that certain inhabitants of the $ulgarian (o(ulation have longer
life s(an than other. &his fascinated him. )ater he discovered that villagers living in the
8ancasus 4ountains were drin"ing a fermented 'oghurt drin" on a dail' basis. He
found that a (robiotic called Lactobacillus bulgaris im(roved their health and ma' have
the longevit' of their lives.
He named it $ulgarian bacillus which is )A$. He suggested it is (ossible to modif' gut
flora b' re(lacing harmful microbes with useful microbes. Bifidobacteria first discovered
b' Henr' tissier *wor"ing in Pasteur institute, from a breast fed infant. He observed the
clinical benefits from treating diarrhea in infants with bifido bacteria.
!erman (rofessor Alfred nissle isolated on the 3.coli strain from the feaces of a soldier
who was not affected from acute gastrointestinal infections shigellosis *during the
1
outbrea" of shigellosis in 1517,. Probiotics term was 1st coined b' Werner "ollath in
159:.
2
&able 1; -ew e<am(les of (robiotics.
Sr.N
o
Genus Species Strains
1 Lactobacillus L.bulgarius reference
symbiosis
585
L.casei YIT 9018,
AT5!10!
L.r"amnosus ##,
AT5!10!
L.$o"nsonii la%1
L.&lantarum L&'99(,
)cfs1
L.acido&"ilus L1'85
L.fermentum *%1+
L."el(ecticus B0'
L.&aracasei *L +!1
L.reuteri ,-'11'.//
'
2 ,tre&tococcus ,.t"ermo&"il
us
,85
3 Bifidobacterium B.animalis -0 11!010
B.bre(e 0I/B8801
B.longum 0'105,
-23I3A

B.infantis *osell 5'
$.adolescenti
s
A&88
1970:
:
$.lactis $b.02+ lafti
$5=+
/0 10
$. $ifidum $b.11
=
2. Health beneit o probitics.
)ive microorganisms having thera(eutic benefit for the host is referred as
Probiotics.Probiotics are usuall' recommended to strengthen immune s'stem of host
and for maintaining gut flora.
>suall'+ the' are harmless but in some rare cases. *3.g.in immunocom(romised
(atients,+ it can cause infection.
Probiotics are "nown for curing man' diseases li"e;.
6. 6nflammator' diseases and bowel s'ndrome
66. 8ancer
666. 8onsti(ation
6?. 4ucosal immunit'
?. Allerg'6
?6. 8ardiovascular diseases
?66. >rogenital tract disorders
?666. $acterial vaginosis
6@. Aeast vaginitis
@. >&6
Dierent probiotics an! their health beneit."
a. Bifidobacterium lactis. regulates digestion s'stem
b. bifidobacterium infatis. (romotes digestive health
c. lactobacillus rhamnosus. restore and maintain normal gastrointestinal floraB
(reventC treat oral candidiasis and diarrhea due to antibioticsB managment of
her(s stomatitis.
9
d. lactobacillus acidophilus.(romotes and maintains a health' and balanced
digestive s'stem.
e. lactobacillus GG. im(roves digestion and digestive health+(revent gas and
bloating+ su((ort immune s'stem and well being and reduce travel associate
digestive com(laints.
f. lactobacillus bulgaricus/ L.casei. strenghen bod'Ds defenses .
g. saccharomyces boulardii. (rotect against digestive imbalance due to antibiotic
travels+stress+ diet.
h. lactobacillus helveticus/bifidobacterium longum. balances gut flora to
maintain health+decrease stress+related digestive s'm(toms.
Alt"oug" &robiotic mec"anism of action on inflammation is not )ell documented,
t"ere are se(eral &ublications on control of inflammation using &robiotics. 4it" t"is
bac5ground t"e aim of t"is re(ie) is to list and understand t"e mec"anism of
inflammation control by &robiotics.
3. Inla##ation$" 6t is a (rotective reaction of bod'Ds immune res(onse which aim to
remove harmful foreign substance. 6t actuall' aim to clear u( the infection b' clearing
damage cells+ (athogens etc.
6nflammation is usuall' induced b' chemical mediators+ such as c'to"ines+ induced b'
damage host cells. 8ardinal signs of inflammation are heat+ redness+ swelling+ (ain and
loss of function. -igure 2 shows the s'm(toms of inflamation. Si%niicance o
inla#ation
&i% 2 ;.Toes inla#e! b' chilblains.
(. )echanis# o Inla##ation$"
E
0ecognition of infection;.
&oll li"e rece(tors *&)0s, recogni2e infection. &)0s detect (athogen associated
molecular (attern li"e )PF or (e(tide which is im(ortant for their survival and bind with
it.After ligand binding and conformational change of &)0s +it recruit ada(tor (rotein 4'
/GG and undergo 4' /GG de(endent (athwa'.
4' /GG de(endent (athwa';
4' /GG recruit 60AH 1+ 60AH 2 which (hos(hor'late and activate the (rotein
&0A-E.&his trafE degrade itself as well as (rotein &AH1 for the binding to 6""$. &his
&AH1 further (hos(hor'lates 6""$ which when (hos(hor'late 6"$+cause its degradation
from 1-"$ and allowing 1-"$ to transcri(tion into the cell nucleus and activate
transcri(tion and inflammator' c'to"ines.
0elease of (roinflammator' c'to"ines;
&ranscri(tion and translation of genes induce the e<(ression of (roinflammator'
c'to"ines such as 6) $eta+6) 0+&1-.al(ha and other.
6n conIuction with chemo"ines+these (roteins facilitate the recruitment of effector cells
such as monoc'te and neutro(hils to the site of infection b' chemota<is.
4ast cells and macro(hages (romotes this migration b' releasing histamine+
leu"otrines and (rostaglandins.
1eutro(hils secrete 0OF and various (roteinases which is descructive to both (athogen
and host which ultimatel' leads to inflammation.
*. Sta%es o inla##ation
Acute inflammation% 6t is a com(le< (rocess of bod's immune res(onse that (rotect
and heal the bod' following infection.6t actuall' aims to im(rove blood flow to the inIured
(artb' local dilation of blood vessel as well as b' increasing vessel
(ermeabilit'.Fignaling molecules and different chemoattractants are released b' mast
cells+(latelets+ and other resident cells at the site of infection that recruit leu"oc'tes *e.g
7
neutro(hils,to the inIured area.1eutro(hils is the first leu"oc'te which a((ear at the
affected area.&hsese cells release non.s(ecific to<ins such as su(ero<ide radicals+
h'(ochlorite and h'dro<'l radicals which (hagoc'tose and "ill invading
microorganisms.&hese 0OF "ill (athogen as well as also damage adIacent
cells.1eutro(hils release c'to"ines+ including interleu"in.1+interleu"in.E and tumor
necrosis factor.al(ha and others which in turn induce liver to s'nthesi2e various acute
(hase reactant (rotein as well as s'stematic inflammator' res(onse *e.g.fever,.
Chronic inflammation.if immune res(onse against inIur' (ersists for longer
(eriod+inflammation can last da's+months and even 'ears which lead to chronic
inflammation.4onoc'teand macro(hages are (rimar' mediators of chronic
inflammation.when monoc'te leave the blood stream and after entering tissue it mature
into macro(hages.&hese macro(hages (hagoc'tose microorganisms+older cells and
foreign cells./ifferent chemicals mediators li"e 6).1+&1-.al(ha etc are released b'
macro(hages that sustain (ro.inflammator' res(onse which is accom(anied b'
l'm(hoc'tes at later stages that invade the affected or damage tissues.-urther on+virus
infected cells are "illed b' & l'm(hoc'tes whereas $ l'm(hoc'tes (roduce antibodies
that target s(ecificall' invading microorganisms res(onsible for destruction.0OF and
(rotease*release b' macro(hages and other leu"oc'tes, not onl' destro' source of
inflammation but also harm bod's own health' tissues.6nfact+tissue damage is sure
sign of chronic inflammation.6n some cases+ bod' is unable to re(air tissue damage and
the inflammator' (rocess continues.
8hronic inflammation is not a bod's normal (rocess and does not benefit the bod' and
in fact it is res(onsible for number of disease. &issue damage that occurs during the
inflammator' res(onse must be activel' cured otherwise it can lead to man' severe
diseases.
&able 2$Co#parison o +cute an! Chronic inla##ation.
+cute Chronic
Causati,e a%ents harmful bacteria or
inIur' to
tissue
non degradable
(athogens
that cause (ersistent
G
inflammation+
infection with some
t'(es of
viruses+(ersistent
foreign bodies
)a-or cells
in,ol,e!
mainl'
neutro(hils+baso(hi
ls
*in the
inflammator',+and
eosino(hils*res(on
se to
(arasites and
worms,+and
mononuclear cells
*macro(hages+
monoc'tes,
macro(hages+l'm(hoc'te
s+
(lasma
and fibroblasts.
.ri#ar'
#e!iators
eicosanoids+
vasoactive
amines
reactive o<'gen s(ecies+
h'drol'tic en2'mes+
6-1.gamma and other
c'to"ines+growth factors.
Duration the inflammation
either gets
better+develo(s into
an
abscess
or become a
chronic
inflammation.
the destruction of tissue+
thic"ening
and scarring of
connective
tissue*fibrosis,+
death of cells or tissues
*necrosis,.
Outco#es short lived+onl' a
few da's
from several months to
'ears
.roble#s associate! /ith chronic inla##ation.
5
Co##on #etho!s to control inla##ation
0. .RO1IOTICS IN CONTRO22ING IN&2+))+TION$"
4an' different (robiotics are recommended for curing chronic inflammation as given in
&able 2.
Lactobacillus rhamnosus gg% decreases &1- al(ha induced 6).G (roduction b' caco.
2 cells via interference with 1-" b activation.
Lactobacillus sp.% increase e<(ression of 4>8 2.
L.acidophiles% b' secreting molecules which bloc"s uorum sensing signalling.
Bacillus subtilis%secrete uorum sensing molecules which induce e<(ression of
c'to(rotectant heat shoc" (rotein. *heat shoc" (roteins e<(ression is increased when
are e<(osed to elevated tem(ratures or other stress.
4ost of the studies of (robiotic control of inflammation are conducted using
6$/ as the model+ hence this review will concentrate on 6$/.
Control o inla##ator' bo/el !isease3I1D4 usin% probiotics .
Inla##ator' bo/el !isease" 6$/ is a chronic inflammator' disorder of the intestine.6t
has two entities; >lcerative colitis *>8, and crohns disease *8/,+ collectivel' "nown as
6$/.
6lcerati(e colitis768.6t is an inflammator' disease of the large intestine or colon.6n this+
>lcers develo(s and inner lining of the intestine also become inflamed.6n man' cases+ it
can lead to diarrhea.6f lining of the colon get damage+ mucus and blood ma' a((ear in
the stool.
ro"n9s diseases7-8% 6t differs from ulcerative colitis in the areas of damage of bowel it
involves.6t mostl' affects the last (art of small intestine i.e. terminal ileum and (arts of
the large intestine.However+it is not limited to these areas and can attac" an' (art of
digestive trac".
8/ involves the entire bowel whereas >8 affects onl' the lining onl' the bowel.
10
-ig :;. com(arision of health' colon and inflamed ulcerative colitis colon.
Si%ns an! s'#pto#s.
/iarrhea and abdominal (ain is the most common s'm(toms of both ulcerative colitis
and crohns disease. /iarrhea can range from mild to severe. At times those with 6$/
ma' also be consti(ated. 6n >8+ consti(ation can be a s'm(tom of inflammation of the
rectum whereas with 8/+ it can be a result of a (artial obstruction in the intestine
*stricture,.
6n some cases+ 6$/ also might dela' (ubert' or cause growth (roblems for some "ids
and teens as it can interfere with them getting nutrients from foods.

-ig =. 8om(arision of >lcerative colitis and 8rohns colitis.
Role o bacteria in I1D.
$acteria (la' a ver' im(ortant role in 6$/. Feveral e<(erimental evidences are there
which (roves that enteric flora is res(onsible for (athogenesis of UC an! CD.
&his can be e<(lained as.
11
1, 6nflammation incidence in this t'(e of disorders is seen more in the area
with high luminal bacteria concentration *0ef.,.
2, 6n the case of 6$/ (atients+ growing evidence suggest that there is a
geneticall' determined loss of immunological tolerance to commensal
bacteria *0ef,.
:, 3vidence (ointing to the interaction of genes+ immunit' and bacteria has
emerged during the (ast half decade and the evidence is (articularl'
noticeable in the case of a series of (ordic+ engineered and geneticall'
determined animal models of 6$/ *0ef,.
&hus+ number of microbial agents are concerned as initiating factors in the
(athogenesis of 6$/. &hese include /ycobacterium &aratuberculosis, measules (irus,
listeria monocytogenes and adherent :.coli.
&his discover' of the role of enteric flora as a (art of common (athwa' to clinical 6$/
has led to revive interest in and increasing scientific assessment of (robiotic
modification of the lumen bacterial environment for thera(eutic reasons.
.robiotic therap' in I1D patients.
Feveral evidence from animal models and clinical observation have aid the e<amination
of wide range of (robiotics strain for treating 6$/. 1umber of (ublished studies have
re(orted the efficac' of Lactobacillus casei strain ## *)!!, for treating 6$/ *0ef,.
According to 4alin et al+ *'ear, consum(tion of )!! in (ediatric 8/+ increases the gut
6gA level which further pro#ote %ut i##unolo%ical barrier. !u(ta et al. 3Year 4
re(orted im(roved clinical outcome and better intestinal (ermeabilit' in an o(en labeled
stud' with (ediatric 8/ (atients. 6n this stud'+ )!! and fructoligosaccharide were
administered to the (atient with pouchitis. $eneficial effect was seen when (atient
were administered with (robiotic.(rebiotic mi< as an adIuvant to antibiotic thera('.
According to Hruis et al. 3'ear4 oral administration of (robiotic :.coli strain 1issile 1517
as a maintenance treatment remission showed no difference in rela(se rate when
com(ared with (atient on #esala5ine.
?F)J:+ a mi<ture of four )actobacilli strains *Lactobacillus &lantarum+ Lactobacillus
casei+ Lactobacillus acido&"ilus, Lactobacillus delbruec5ii ss&. bulgaricus,+ three
biKdobacteria strains *Bi;dobacterium infantis, Bi;dobacterium bre(e, Bi;do%bacterium
12
longum,+ and one strain of ,tre&tococcus sali(arius s&. t"ermo&"ilus+ has been used to
treat >8+ 8/+ and (ouchitis (atients *ref,
&he 'east ,acc"aromyces boulardii has been successfull' used for the (revention of
antibiotic.associated diarrhea and in the treatment of other t'(es of diarrhea. 6n a
randomi2ed double.blind trial with :2 8/ (atients in clinical remission receiving either
mesalamine or mesalamine (lus F. boulardii+ clinical rela(se was observed E.29L of
(atients receiving mesalamine (lus F. boulardii versus :7.9L in the mesalamine alone
grou(. &hus ,. boulardii is ver' effective for treating 6$/.
1:
.robiotic #echanis# o action in inla##ator' bo/el !isease3I1D4.
Probiotics bacteria (rovide benefits to host in mainl' two wa's *i, b' su((ressing the
(athogen growth in the intestine and *ii, b' boosting of the host immune res(onse and
barrier function through interaction with e(ithelial and immune cells of both small and
large intestine.
Hence+ it is ver' clear that that wor"ing of immune s'stem at both a s'stematic level
and a mucosal level can be controlled b' bacterial strains in the intestine. 4ucosal
immune s'stem is managed b' active constituents of (robiotic bacteria that include
en2'mesB secreted (rotein factorsB bacterial formulated (e(tides such as 1.form'l
methionine.leucine.(hen'lalanine *f4)P, and li(o(ol'saccaride*)PF, as well as
(e(tidogl'can cell wall constituents including the muram'l di(e(tide*4/P, gamma./.
glutam'l.meso.diamino(imelic acid *i3./AP,+ and bacterial deo<'ribonucleic acid
*/1A,.
-ive (robiotic mechanisms of action are re(orted for controlling 6nflammator' bowel
disease *6$/,.
1, 0ece(tor com(etition+ whereb' (robiotics com(ete with microbial (athogen for
limited number of rece(tors (resent on the surface e(ithelial. 36%4
2, Probiotic release antimicrobial factors such as lactic and acetic acid+ h'drogen
(ero<ide and bacteriocins that induce the su((ression of (athogen growth.
Feveral (robiotics are re(orted for (roduction of antimicrobials. Gi,e na#es
:, 3nhancement of mucosal barrier function b' (robiotics. )ore ino
=, Potential immunomodulation or stimulation of immune function of gut.associated
l'm(hoid and e(ithelial cells. )ore ino
9, Probiotics induced &.cell a(o(tosis in the lamina (ro(ria. )ore ino
Conclusion
What are (robioticsM
How (robiotics control the inflammation M
What is the future of this stud'M
1=
Although there are evidences of control of inflammation b' (robiotics+ it needs further
detailed studies to rule out the side effects of (robiotic bacteria.
19
&able :. .robiotic therap' in I1D patient
F.n
o.
Probiotic
microorganism
&'(e of
stud'
&rial outcome 0eference
1 )actobacillus
!!
Human trial.
O(en stud'.
1N1=.
Human
trial .1N=.
O(en trial
Human trial.
O(en.
labeled
stud'. 1 O
10 (er grou(
6ncrease in gut 6gA
res(onse.
6m(roved intestinal
(ermeabilit' and
8/A6.
Probiotic and
(rebiotic
fructooligosacchari
de induced
remission in
(ouchitis trial when
administered as
adIuvant to
antibiotic.
4alin et
al*=E,
!u(ta et al.
*=7,
-riedman et
al. *=G,
2 3. coli strain
1issle 1517
0andomi2ed
+ double.
blind human
trial. 1N120
0andomi2ed
+ double.
blind human
trial. 1N11E
0andomi2ed
+ double.
blind human
Patients with active
>8 demonstrated
similar rela(se
rates com(ared
with (atients on
mesala2ine.
8onfirmed result
from
0emission
maintained in
(atients receiving
(robiotic with
Hruis et al.
*=5,
0embac"en
et al. *90,
4alchow et
al. *99,
1E
trial. 1N2G steroids com(ared
with steroids and
(lacebo.
: ?F)J:
controlled
0andomi2ed
double.blind
(lacebo.
human trial.
1N=0
O(en trial.
1N 20.
0andomi2ed
double.blind
(lacebo.
controlled
human trial.
1N=0
4aintenance of
remission in
chronic (ouchitis.
19L rela(se
com(ared with
100L in control
grou(.
4aintenance of
remission in >8
(atients.
Patients with >8
had 20L remission
when given
rifa<imin and
?F)J: com(ared
with =0L in
mesalamine
treated grou(.
!ionchetti et
al. *12,
?enturi et al.
*1:,
8am(ieri et
al. *1=,
= Faccharom'ce
s boulardii
Human trial.
/ouble.blind
stud'. 1N20
0educed freuenc'
of bowel
movements in >8
(atients.
0ela(se observed
in E.29L >8
(atients receiving
(robiotic (lus
mesalamine
com(ared with
:7.9L on
mesalamine alone.
Pein and
Hol2 *9E,
!uslandi et
al. *9=,
17
1G