IMPORTANCE OF PROBIOTICS IN GASTROINTESTINAL TRACT

Kiran Konain1, Sadia2, Turfa Nadeem3, Adeed Khan2 Warda Iqbal2, Kainat Jamil2, Saleha
Qazi2, Ruby Khan2, Arsalan4, Amir Javed4
1
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
2
Centre of Biotechnology & Microbiology, University of Peshawar, Peshawar, Pakistan.
3
Department of Pharmacy, The University of Lahore, Islamabad Campus, Pakistan.
4
Institute of Biotechnology & Genetic Engineering, The University of Agirculture, Peshawar,
Pakistan.
*Corresponding author’s email: kiran.konain@hotmail.com

Abstract

Probiotics are those microorganisms that are incapable of causing any disease and when
consumed, they impact the host positively. Treatment of GIT infections with antibiotics can
affect this microflora of GIT which leads to several complications such as different colorectal
cancers, constipation, allergic reactions and others. Thus, the addition of these useful
bacterial species to the GIT may be an effective method to prevent such disease and also to
restore the microbial equilibrium. Mostly used bacterial genera in the preparation of
probiotics are Escherichia, Bacillus, Streptococcus, Bifidobacterium, Lactobacillus,
Bifidobacterium and Enterococcus. Moreover, few strains of fungi belonging to
Saccharomyces are utilized in probiotics preparation. In this review, we tried to assess the
significance of probiotics in gastrointestinal tract and studied their adverse effects.

Keywords

Probiotics, gastrointestinal infection (GIT), microflora, microbial equilibrium

 INTRODUCTION

Gastro intestinal tract (GIT) infection is one of the significant reasons of deaths around the
globe due to severe dehydration and diarrhea. Death rate of children under age of five are
about 1,575,000 from the inspection done in 2006 (Lopez, Mathers et al. 2006). Micro-
organisms live in every habitat including the human body in mouth, gastro-intestinal tract and
even on the skin. These microorganisms have such an association in which one organism
depends on another organism for nourishment or different advantages without harming or
helping it. Within the human body, higher concentrations of these commensals micro-
organisms are found in the gastro-intestinal tract. GIT have more than 500 different species of
bacteria. Among them, some have positive effect on human health (Vanderhoof and Young
1998). It has been assessed that microscopic organisms represent 35-50% human colon
volume and comprises of Clostridium, Bifidobacterium, Lactobacillus, Bacterioides,
Fusobacterium, Peptococcus, Eubacterium, Eschericha, Veillonella and Peptostreptococcus
(Vanhoutte, Huys et al. 2004, Ley, Peterson et al. 2006).

Influence of Probiotics on Humans and Animals Health

A specialist board authorized by WHO and Food and Agriculture Organization (FAO)
characterized probiotic as "live micro-organisms," which, when given in satisfactory sums
gives a medical advantage to the host (FadlAlla 2015). Probiotics can influence both human
and animal health by modulating micro-biota of intestine at present, food ingredients of the
particular live microbes and their impacts on human wellbeing are concentrated on both
inside of food matrices. Furthermore, as single or blended culture preparation (Timmerman,
Koning et al. 2004, Collado, Meriluoto et al. 2007). and micro-organisms should have
following properties for them to be used as probiotics: i) it should be safe to use; ii) it should
be able to resist the action of hydrochloric acid, bile and pancreatic juices; iii) it should not be
carcinogenic; iv) it should have the ability to survive in both in acidic as well as basic
environment of stomach and duodenum respectively; (Gupta and Garg 2009) v) should have
positive effect on host; vi) should not be pathogenic and toxic; (Collado, Isolauri et al. 2009)
vii) should be able to stimulate immune system and can produce lactic acid. Foods that
mainly contain lactic acid bacteria include cheese, wine, fermented milk, sausages and fruit
juices (Gupta and Garg 2009).
 1: should be safe to use
2: withstand the action of hydrochloric acid, bile and pancreatic juices
3: should be non-carcinogenic and non-pathogenic
4: should be able to persist both in acidic and basic environment of stomach and
duodenum
5: should effect host positively
6: can stimulate immune system
7: can produce lactic acid
Table 1. Criteria of an ideal microorganism as probiotics

Characteristics of Probiotics

Mode of action

The consumption of probiotics has several positive effects such as by the regulation of micro
biota it can enhance the intestinal tract health, immune system stimulation, augment the
bioavailability of nutrients, bringing down the risk of some maladies and reduction in the
signs related to intolerance of lactose. Different mode of actions has been suggested that
describe the positive effect of using probiotics such as altering the pH of gut, completion with
the pathogen for binding receptor sites, producing anti-microbial compounds, production of
lactase and stimulation of immunomodulatory cells. However, the specific mechanism used
by probiotics to influence their effects is still unknown (Parvez, Malik et al. 2006). Different
strains of bacteria differ on the basis of their effect on health. Keeping in mind the possible
targets of probiotic, they are designed and applied to specific diseases. The interaction of host
with microbes can be of following type: i) interaction of microbe-gut epithelium; ii)
interaction between microbe-immune system; iii) microbe-microbe interaction.

Adhesion
Adhering to the mucus of intestine is basic requirement for the colonization and is important
in the modulation of immune system (Beachey 1981, Schiffrin, Brassart et al. 1997, Juntunen,
Kirjavainen et al. 2001). Various investigations uncover that probiotics can competitively
restrain the pathogen attachment like that of Staphylococcus aureus, Escherichia coli,
Clostridium difficile, Salmonella, Listeria monocytogenes, and Bacteroides vulgatus (Bernet,
Brassart et al. 1993, Aissi, Lecocq et al. 2001, Gueimonde, Noriega et al. 2005, Collado,
Gueimonde et al. 2006, Gueimonde, Jalonen et al. 2006, Collado, Meriluoto et al. 2007). It is
also reported that some bifidobacteria and lactobacilli share carbohydrate binding
specificities with some of the entero pathogens(Fujiwara, Hashiba et al. 2001). It is
additionally revealed that some bifidobacteria and lactobacilli impart starch restricting
specificities to a portion of the entero pathogens. For the most part, it is trusted that the
strains of probiotics can repress pathogenic bacteria adhesion by steric hindrance at intestinal
absorptive cells pathogen receptors. Thus, the main basis of selection of new probiotic strain
is adhesion.

Anti-microbial substances

The metabolites that are manufactured by lactic acid bacteria having antimicrobial effects can
be partitioned into two sets (i) bacteriocins that are antimicrobial proteins (>1.000 Da) and
(ii) compounds with low molecular mass (below 1,000 Da) (Niku‐Paavola, Laitila et al. 1999,
Chen and Hoover 2003).
Probiotics produce acids from the fermentative metabolism of carbohydrates are considered
as the main antimicrobial compounds which is accountable for their inhibitory effect against
pathogens (Ibrahim and Bezkorovainy 1993, Bruno and Shah 2002). Probiotics also show
antagonistic effects against different pathogens belonging to genus Salmonella, Escherichia,
Listeria, Shigella, Clostridium, Candida, Helicobacter and Campylobacter (Touré, Kheadr et
al. 2003, Gagnon, Kheadr et al. 2004, Servin 2004, Collado, Gonzalez et al. 2005, Collado,
Hernández et al. 2005).

Immunomodulation
Studies show that use of probiotics can repair and prevent damage to the intestine. Probiotics
can regulate and stimulate natural as well as acquired immune response by interaction with
mucus associated lymphoid tissue. This interaction has a high importance for human
wellbeing and could affect infectious diseases such as allergic diseases, some types of cancer,
a variety of intestinal inflammatory diseases and auto immune disorders. Probiotics bind with
the receptors present on the epithelial cell surface, inducing cellular and humoral immune
response that direct to both pro-inflammatory and anti-inflammatory responses. There are
expanding evidence that couple of probiotics can produce defensive immune response
enough to raise resistance to microbial pathogens (Cross 2002). Studies done on human and
animal shows that different probiotic strains can affect immune system differently. These
effects also depend on the immune status of the host as well as the dose given (Madsen,
Cornish et al. 2001).

Typical human gut micro-flora as a source of probiotics

Human intestine is accompanied by trillions of microbes that forms a complex community
influencing the sensitivity towards diseases and normal physiology by a complex interaction
between host and the microbes (Lozupone, Stombaugh et al. 2012). Although these microbes
are present all through the intestine, the high concentration and metabolic activity of these are
present in the large intestine(BENNO and MITSUOKA 1986, Salminen, Bouley et al. 1998).
Data obtained from cultures shows that complex micro-flora present in mouth consists of
facultative anaerobes which can include bacteroides, yeasts, streptococci and lactobacilli.
The upper portion of bowel has scanty micro-flora up to 10 5 colony forming units/ml. From
ileum and onward, the concentration of these bacteria’s increases slowly and reaches up to
1011 to 1012 colony forming units/g within the colon. Approximately 500 various species of
microbes exists, although on a quantitative basis 10-20 genera might predominate in healthy
human micro-flora including Clostridium, Bifidobacterium, Bacteroides, Peptococcus,
Lactobacillus, Veillonella, Peptostreptococcus, Fusobacterium, Escherichia and Eubacterium
(BENNO and MITSUOKA 1986). Any change in the composition of gut microbes can lead to
diseases like gastric ulcer, colon cancer, auto-immune disease, cardiovascular diseases,
diabetes type 2 and obesity(Vyas and Ranganathan 2012). Probiotics can have an immediate
antimicrobial impact. Truth be told, a few strains/species in probiotics can specifically inhibit
or kill the development of pathogenic microscopic organisms like bacteria through creation of
antimicrobial components, for example, bacteriocins, proteases coordinated against bacterial
toxins, or through avoidance of pathogens by basically sticking to epithelial cells (Oh, Kim et
al. 2000, Corr, Li et al. 2007, Quigley and Flourie 2007).

CLINICAL IMPORTANCE OF PROBIOTICS

Diarrhea associated with antibiotics

About ≤ 20% of patients suffer from diarrhea after taking antibiotics. This is due to the
imbalance in microbes that can cause decrease in the flora, the result is resistance to
colonization and decrease in the capacity of fermentation of the colon(Ligny 1975). Even
though new antibiotics that are effective against a large verity of micro-organisms with lesser
side effects, have been developed, still antibiotic associated diarrhea ranges from 3.2-29/100
patients(Bartlett 1992). Antibiotics that contain anaerobic bacteria (penicillin, cephalosporin
and clindamycin) are associated with more antibiotic associated diarrhea rates. Several meta-
analysis reports published recently showed that use of probiotics decreased the occurrence of
AAD (Cremonini, Di Caro et al. 2002, D'Souza, Rajkumar et al. 2002, Szajewska and
Mrukowicz 2005, McFarland 2006). Mostly used probiotics are lactic acid bacteria,
S.boulardii and many combinations of LABs administer in 107 to 1011 doses with duration of
5-49 days parallel to the duration of an antibiotic therapeutic procedure. One of the meta-
analyses showed that L. rhamnosus, S.boulardii and many mixes of two dissimilar probiotics
are most effective against AAD (McFarland 2006).

Diarrhea Linked with Infections

Use of probiotics can reduce the duration of infectious diarrhea in both children and adults.
From different trials, it was shown that there was about 30 hours decrease in symptoms
durations. From Cochrane review involving 23 studies with about 2000 participants out of
which 352 were adults, it was deduced that use of probiotics reduces persistent diarrhea risk.
Only two studies used S.boulardii while mostly tested probiotics (18 out of 23 studies) were
LABs (Allen, Okoko et al. 2003). The effectiveness of probiotics in treating infectious
diarrhea has also been evaluated in a meta-analysis which included total of 63 studies out of
which 56 were infant/young children. Altogether, probiotics reduced the duration of diarrhea
by 24.76 h (95% CI 15.9–33.6 h), the risk for diarrhea lasting ≥4 days (risk ratio 0.41;
95% CI 0.32–0.53), and reduced stool frequency on day 2 (mean difference 0.80; 95% CI
0.45–1.14) (Allen, Martinez et al. 2010).

Travelers’ diarrhea
A typical health problem among travelers is traveler’s diarrhea. Rates of this diarrhea can
extend from 5 to 50% contingent on destination. A meta-investigation was done on
distributed randomized controlled clinical trials of cases involving traveler’s diarrhea. It was
reasoned that probiotics fundamentally averts the occurrence of traveler’s diarrhea.
Saccharomyces boulardii and a blend of Bifidobacterium bifidum and Lactobacillus
acidophilus had noteworthy efficacy (McFarland 2007). Acute diarrhea occurs to about half
of travelers who visit high-risk areas. Although many cases are mild and self-limiting, there is
a considerable morbidity(Wood, DuPont et al. 1993, DuPont 1997). Different studies were
conducted with the use of probiotics. Few studies involved lactobacilli which showed
negative results however, 4 studies used variety of probiotics that showed positive results. 94
Danish tourists who participated in a trip of 2-wk to Egypt, were treated with a mixture
of Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacteria, and S.thermophilus or
a placebo in a randomized study. The rate of traveler's diarrhea was decreased from 71%
(very high) to 43% (Black, Andersen et al. 1989).

Inflammatory bowel-disease

Inflammatory bowel diseases are characterized by recurrent or chronic intestinal infections

with an unknown cause. These disorders include chronic disease, ulcerative colitis, and
pouchitis. The process for maintenance and initiation of this inflammatory process has not
been discovered, but main theory stated that inflammatory bowel disease results from an
abnormal response of the host to the some floral members of an intestine or from mucosal
barrier defect(Ruseler-van Embden, Schouten et al. 1994, Sartor 1995). Different studies
show the effect of probiotics on inflammatory bowel disease in animals. The administration
of L. reuteri in rats prevent the formation of acid induced colitis(Fabia, Ar'Rajab et al. 1993).
In Crohn’s disease, oral bacteriotherapy with L. casei strain GG has shown same effects. In
disease of crowns, there is an increasing number of IgG together with mucosal IgG
deficiency in lesions of tissue. Oral application for ten days of L. casei strain GG led to an
increase in IgA mucosal levels. Results suggest immunological barrier improvement (Malin,
Suomalainen et al. 1996). In open studies 10-d administration of L. rhamnosus GG with the
14 children having inactive or active crohn disease results in increase immunoglobulin a
secreting cells to casein and beta-lactoglobulin indicating interaction within immune system
and probiotic (Malin, Suomalainen et al. 1996). Hotz and Plein conducted a double-blinds,
plot, controlled study of S.boulardii of efficacy on Crohn Disease Symptoms. 20 patients with
moderate, active Crohn disease were assigned randomly to a placebo for 7 weeks or
S.boulardii to a standard treatment. The significant decrease in frequency of disease activity
and bowel movement was observed in the having S. boulardii and not in placebo group (Plein
and Hotz 1993). The efficacy of oral E.coli preparation and mesalazine compared by two
studies (Kruis, Schütz et al. 1997, Rembacken, Snelling et al. 1999) in maintenance of
remission of ulcerative colitis. 120 patients with inactive ulcerative colitis were included in
first study. 11.3% of the patients treated with mesalazine relapsed after 12 wks as compare to
those 16% who were treated with probiotics. Second study had 116 patients which also
showed that the preparation of probiotic was effective as mesalazine in remission inducing
and relapse prevention (Rembacken, Snelling et al. 1999). Many studies in Europe are testing
the probiotics effect on inflammatory bowel disease.

Irritable bowel syndrome

This syndrome is described by a stomach torment, change in the habit of bowel and bloating,
with a nonattendance of any clear mucosal abnormality and flatulence(Thompson, Longstreth
et al. 1999). Probiotics also including bifidus milk or acidophilus relieve constipation in some
patients which were not controlled (Marteau, Pochart et al. 1993). In a random placebo-
controlled study which comprises 34 patients, Maupas et al., (Maupas, Champemont et al.
1983) observed that S.boulardii reduced functional diarrhea but did not increase other
symptoms of bowel syndrome. Halpern at al (Halpern, Prindiville et al. 1996) suggesting in
random, crossover, double-blinds that heat killed lactobacilli administration for 6 wk was
more effective than placebo in irritable bowel syndrome symptoms relieving. Hentschel et al.,
(Hentschel, Bauer et al. 1997) suggest the efficacy of preparation of 2 probiotic having E.coli
and lactobacilli in 126 patients affected by nonucler dyspepsia and didn’t observe
amelioration. S. boulardii minimize the duration of diarrhea activated by tube feeding in 3
trials (Tempé, Steidel et al. 1983, Schlotterer, Bernasconi et al. 1987, Bleichner, Blehaut et al.
1997). Recently the study was double blind and compared the placebo in 128 critically ill
patients of tube-fed with 2g of S.boulardii/day (Bleichner, Blehaut et al. 1997). Probiotic
treatment reduced the percentage of diarrhea days experienced by patients from 18.9% to
14.2% (p=0.007). The open 2 study results that lactobacilli may have efficacy against the
overgrowth of small intestinal bacteria (Simenhoff, Dunn et al. 1995, Vanderhoof, Young et
al. 1998) but S. boulardii is not effective in random placebo controlled study (Attar, Flourié et
al. 1999). Diarrhea is an adverse nearly constant effect of pelvis irradiation. A control
randomized study showed a decrease in patients with diarrhea during pelvic irradiation by
Salminen et al., (1998) in those patients receiving L. acidophilus NDCO 1748. Some past
Open trails have been conducted in which freeze dried lactic acid bacterial cultures were used
for the same symptoms (Salminen, Elomaa et al. 1988) .such therapeutic effects needs to be
further studied Elmer et al., discovered that S. boulardii may has effect when taken in high
doses in some patients with chronic diarrhea related with HIV and before conclusions further
evaluation should be drawn (Elmer, Moyer et al. 1995).

In the treatment of IBS, the meta-analysis of clinical features of probiotics was led by
Moayyedi and his colleagues. In this study, 18 randomized clinically controlled trials
including 1,650 IBS suspects were identified and the examining products include
Streptococcus (1 study), lactobacillus (6 studies), Bifidobacterium (3 studies), and different
combination products (9 studies) (and one trail was reported on both Bifidobacterium and
lactobacillus). Out of these ten (n= 918) concluded results as a variable dichotomous, in these
studies IBS symptoms were reduced by probiotics (persisting risk of symptoms in treatment
group 95% CI (0.57-0.88) and with number treat of four needed. Total 15 trials reported
results as continuous variable, grouping for meta-analysis. These trails examined that
probiotics had high significant effect in improvement of IBS symptoms as compared to
placebo. Differences between different probiotics were shown in this meta-analysis with
Bifidobacterium (2 trials involving 422 suspects), streptococcus (1 trial involving 54
suspects), lactobacillus (3 trials involving 140 suspects), and different combination products
(four trials involving 302 suspects) in which all were showing benefits. In an improvement of
individuals symptoms, probiotics had good effect in improvement of bloating, flatulence, and
pain sources (Moayyedi, Ford et al. 2010).

In adults, varieties of studies showing that L. rhamnousus GG, B. infantis, and the different
mixture of probiotics as L .rhamnosus LC705, L. rhamnous GG, Propionibacterium
freudenreichii JS, and B. breve Bb99 are effective in minimizing the IBS symptoms. While in
infants there is decrease in abdominal distention but there is no decrease in abdominal pain
by L. rhamnosus GG (Bausserman and Michail 2005, Kajander, Hatakka et al. 2005,
Gawrońska, Dziechciarz et al. 2007, Kajander, Myllyluoma et al. 2008).

Allergic diseases

The reaction of hypersensitivity initiated by mechanisms of immunology is known as allergy,

on the basis of immunological mechanisms that are involved the allergy is classified into non-
lgE-mediated allergy and IgE mediated allergy (Johansson, Hourihane et al. 2001). The
allergic disease development is related to Microbiota aberrancies (Kalliomäki, Salminen et al.
2001, Kalliomäki and Isolauri 2003). In infants atopy development is detected due to reduced
ratio of Bifidobacteria to clostridia (Kalliomäki, Salminen et al. 2001) and patients with
allergy are often more colonized with staphylococcus and clostridium and have few
Bifidobacterium and Enterococcus than in non-allergic persons (Kalliomäki, Salminen et al.
2001, Björkstén 2004, Watanabe, Matsuoka et al. 2004). Composition differences in gut
micro-biota may manipulate the manifestation and development of atop. Higher risk of
eczema development has been assigned to early colonization of Escherichia coli. Clostridium
difficile is associated with recurrent wheezing, allergic sensitization in infants and eczema
(Penders, Thijs et al. 2007).

Disease of atopy arises from abnormal responses of immune system to allergens present in
the environment which leads to inflammatory allergic response (Stone, Prussin et al. 2010).
An allergic skin disease known as Atopic dermatitis (AD) is widely common in kids from
Western Europe and the US (Larsen and Hanifin 2002). Such patients suffering from this
disease have maximum number of Clostridium and S. aureus in their colon and have a
minimum number of Bacteroides, Enterococcus, and Bifidobacterium. Healthy intestinal
microbiota with high recognition of importance with value of active role of probiotics in the
treatment and prevention of human allergic disease in clinical trials.50% of reduction
occurred in atopic eczema by administration of Lactobacillus GG to high risk
infants(Kalliomäki, Salminen et al. 2001). In other experiments, children were treated for two
months with a whey formula having L. rhamnosus or B. animalis subspecies lactis in Finland
which resulted in improved skin condition. Similarly, results obtained L. rhamnosus plus L.
reuteri were curative (Majamaa and Isolauri 1997, Rosenfeldt, Benfeldt et al. 2003). In
western society spread of atopic diseases has been increasing progressively. Hygiene
hypothesis of allergy came up with the less exposure to microorganisms at an early age
(Strachan 1989). The most effective and earliest source of this type of exposure is related
with the settlement of gut micro-flora. In human allergic disease, the probiotics regulatory
role was first highlighted in the demonstration of the inhibition effect on lymphocyte’s
proliferation and in vitro interleukin 4 generation (Sütas, Hurme et al. 1996, Sütas, Soppi et
al. 1996). The immune-inflammatory response in allergic individuals to dietary antigens were
minimized by probiotics, this partly increases the production of anti-inflammatory cytokines
interleukin 10 (Pessi, Sütas et al. 2000) and also the transforming growth factor beta (Isolauri,
Arvola et al. 2000) which partly control allergic inflammation of gut (Majamaa and Isolauri
1997).

Cancer
Cancer has a great importance in human well-being because of its increasing frequency in
developed nations. The techniques for effectual treatment of cancer under study are
incalculable and not long ago, the utilization of LAB has showed up in this field. Disease
improvement and movement have been comprehensively related with unending irritation
procedures created by outside components, for example, contamination, radiation, uneven
eating regimen, heftiness, tobacco or the introduction to other ecological poisons (Aggarwal,
Vijayalekshmi et al. 2009).

The immune system and endogenous flora play role in carcinogenesis modulation. Probiotics
may influence both of them which lead to investigating the probiotics role in curing and
preventing animal tumors. Different authors have shown that some probiotics may minimize
the enzymes, secondary bile salts and mutagens fecal concentrations which might be involve
in carcinogenesis of colon (Wollowski, Rechkemmer et al. 2001). Not all but some
epidemiological studies suggest that fermented dairy products might have protective effect
against cancer or large colon adenomas (Rafter 1995). LAB organisms are used for the
prevention of colorectal cancer has been found mainly using colorectal cancer murine models
(Aggarwal, Vijayalekshmi et al. 2009). One sample used Bifidobacterium adolescentis which
expressed a recombinant endostatin demonstrated how this protected vector could specifically
repress angiogenesis and tumor development in tumor mice models after its intravenous
administration (Li, Fu et al. 2003).

In a controlled double blind study with 138 patients in 1995, L. casei Shirota preparation had
preventive effect on the rate of bladder cancer after surgery (Aso, Akaza et al. 1994). In a
variety of animals models involving rats and mice which were fed on oligofructose and/or
insulin reduce the fecal water genotoxicity (Klinder, Forster et al. 2004). The numbers of
precancerous lesions which are induced chemically are decreased (Bolognani, Rumney et al.
2001, Pool-Zobel, Van Loo et al. 2002) and also defense function is stimulated. The activity
of NK-cells and IL-10 was also increased (Roller, Caderni et al. 2006). Tumor incidence in
organs (breast cancer in mice and rats, in lungs(Taper and Roberfroid 2002) and large
intestine (Verghese, Rao et al. 2002) were decreased by the addition of 5 to 15% oligo
fructose or inulin to the diet in the long term. This impact was significantly more proclaimed
when a mix of prebiotics and probiotics was given (Femia, Luceri et al. 2002). In the colon of
male Sprague-Dawley rats treated with 1,2-dimethylhydrazine, Xylooligosaccharide appeared
to decrease the quantity of aberrant crypt foci (Hsu, Liao et al. 2004).
Adverse side effects of LAB

LABs are (GMOs) genetically modified organisms and are well stablish in industries such as
food industries and are widely accepted. For its use as a therapeutic agent, important
regulatory concerns are needed to be addressed. LABs are specifically based on expression
systems having selection markers as antibiotic resistance genes (Peterbauer, Maischberger et
al. 2011). The transfer of antibiotics resistance of live vectors to intestinal microbiota has
been discovered but this rare event has not reported in this field however this issue is
important to be considered. LAB as live vectors opens an interesting and vast field of
possibilities but measures related to regulation has to be considered to ensure the used strain
safety. Some innovative selection markers and alternative up till now have already developed,
some of them are tested successfully and positively evaluated by different health authorities
(Vandenbroucke, Hans et al. 2004, Rottiers, De Smedt et al. 2009, Peterbauer, Maischberger
et al. 2011). These safe and alternative selection markers must be explored further that some
of LAB adverse effect have been reported (Ishibashi and Yamazaki 2001, Didari, Solki et al.
2014, Doron and Snydman 2015). This shows that having positive therapeutic effects of such
microorganisms and minimum adverse effect are registered they are not safe completely. This
information should be given importance as the adverse effects observed were in high risk
groups like immune compromised and critically ill patients, hospitalized patients and severely
sick infants. The main harmful effects of LAB described are fungemia, GI ischemia and
Sepsis (Didari, Solki et al. 2014). In vulnerable populations LAB interfere with micro flora
forming opportunistic infections and leads to fungimia, bacterimia or different medical
complication. Other strong evidences shows that using LAB as probiotics has anti-
inflammatory effects however reports also shows pro-inflammatory effects caused by group
of bacteria which means that effect of LAB as probiotics is strain dependent, acting as a
factor to be the therapeutic applications of host strains (Plaza-Diaz, Gomez-Llorente et al.
2014, Villena, Aso et al. 2014).

Obesity

Obesity is seen as one of the real current general health issues and its effect is the most
noteworthy in kids, adding to critical dreariness in adulthood (Owen, Martin et al. 2005). The
progress of metabolic complications connected with obesity amid youth track into adulthood
and builds the danger for diabetes type 2 and early cardiovascular illnesses (Nathan and
Moran 2008). Dangerous elements of obesity in infant involve eating routine, low financial
status, maternal obesity, quick outset weight pick up, and diminished physical action.
Additional to these dangers, a few reports have proposed that the gut microbiota is an
imperative element influencing energy transfer and capacity in adipocytes (Bäckhed, Ding et
al. 2004, Ley, Bäckhed et al. 2005, Ley, Turnbaugh et al. 2006, Turnbaugh, Ley et al. 2006).
Moreover, a late report demonstrated that newborn children with high quantities of the
Bifidobacterium and low quantities of Staphylococcus may be shielded from overabundance
weight gain amid later life(Kalliomäki, Collado et al. 2008). The Bifidobacteria populace
(and most different life forms in the family of Firmicutes) is somewhat lower in people with
obesity than in slim individuals (Schwiertz, Taras et al. 2010). A comparative finding was
accounted for in patients with type 2 diabetes mellitus in correlation with no diabetic patients
(Wu, Ma et al. 2010). These discoveries recommend that Bifidobacteria may have an impact
in the advancement of obesity and its related independently existing medical condition. At the
point when prebiotics like inulin-type fructans were given to mice, these were utilized as
vitality substrates by microorganisms (Cani, Neyrinck et al. 2007, Cani, Possemiers et al.
2009, Dewulf, Cani et al. 2011). The quantity of Bifidobacteria expanded altogether, and
there was a backwards connection with the levels of lipopolysaccharide, glucose resistance
and advancement of fat mass (Cani, Neyrinck et al. 2007, Dewulf, Cani et al. 2011).
Additionally, it has been accounted for how weight control plans in view of a high admission
of protein and/or low admission of sugar or low fat utilization may change the composition of
microbes and activity in the large intestine and consequently affect gut health. Modification
of Micro-biota by utilization of probiotics may offer new headings for preventive and
restorative applications in lessening the danger of obesity and overweight (Bäckhed, Ding et
al. 2004, Cani, Amar et al. 2007, Cani, Neyrinck et al. 2007, Duncan, Belenguer et al. 2007).

Constipation
There are a significant number of reports on the constructive outcomes of fermented dairy
items on constipation (Sanders 1993). Unfortunately, greater parts of the studies were
performed under inadequately controlled conditions. Positive results have been accounted for
in studies with geriatric patients (Alm, Humble et al. 1983). A double-blind crossover
investigation of 50 patients with periodic constipation likewise indicated positive results.
They got 1 g of a LAB preparation (containing 10 L. casei per gram) three times each day.
Amid the treatment time of 30 days, either the medication or a fake treatment was regulated
orally. The general effectiveness rate was 67% (Ogawa, Hirai et al. 1974).

Conclusion:

Probiotics are helpful and are progressively utilized for an assortment of Gastro-intestinal
issue. Probiotics seem to adjust intestinal micro-flora and may apply their effect(s) by
different mechanisms. Numerous types of probiotics exist and it is, by and large,
acknowledged that all probiotics are not made equivalent. Efficacy may be because of a
solitary strain or numerous strains or a mix of distinctive. Probiotics diminish the span of
indications in intense infectious diarrhea. At the point when added to standard treatment,
probiotics don't give extra benefit compared to standard treatment alone. Introduction of
probiotics orally has appeared to fortify the different lines of the gut defense system.
Probiotics likewise fortify non-particular host resistance to microbial pathogens and in this
manner guide in their annihilation. The utilization of probiotics right now lies in lessening the
danger of infections connected with gut barrier brokenness. Probiotics treatment has
effectively advanced in the treatment of a number of conditions. Before bringing probiotics
into routine use, legitimate assessment of these items is crucial.
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