Critically discuss the studies investigating pre and probiotics in people with inflammatory bowel disease

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Prebiotics and Probiotics in persons with IBD
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Table of Contents
Prebiotics and Probiotics in persons with IBD ..............................Error! Bookmark not defined.
Introduction..................................................................................................................................... 3
Pro, Pre and antibiotics in the management of Inflammatory Bowel Disease................................ 3
Prevention of Inflammatory Bowel Disease ................................................................................... 4
Symptoms of Inflammatory Bowels Disease.................................................................................. 4
Roles of Probiotics.......................................................................................................................... 4
Lactobacillus ............................................................................................................................... 4
Escherichia coli Nissle 1917 ...................................................................................................... 5
Saccharomyces boulardii............................................................................................................. 5
The Microflora ............................................................................................................................ 6
The roles of Microflora in Inflammatory Bowel Disease ............................................................... 7
Roles of Prebiotics .......................................................................................................................... 7
Lactulose ..................................................................................................................................... 8
Lactosucrose................................................................................................................................ 8
Oligofructose and inulin.............................................................................................................. 8
Treatment of Inflammatory Bowel Disease .................................................................................... 9
Conclusion ...................................................................................................................................... 9
References..................................................................................................................................... 10

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Prebiotics and Probiotics in persons with IBD
Introduction
A significant research body nowadays exists investigating the role of prebiotics and
probiotics in improving chronic abdominal inflammation. The essay will give an overview of the
use of prebiotics and probiotics in human IBD, prevention and treatment of Inflammatory Bowel
Disease. Inflammatory bowel disease (IBD) comprises of two distinct clinical forms, Crohn’s
disease (CD) and Ulcerative Colitis (UC) (Berg, Clemente, and Colombel, 2015, p.795) with an
unidentified etiology that nonetheless are considered to share nearly undistinguishable
pathophysiological circumstances. Existing reviews summarize the factors perpetuating and
initiating Inflammatory bowel disease, from four essential perspectives: microbial flora role,
barrier dysregulation, immune dysregulation, and genetics. The interaction of the intestinal
microorganisms with the mucosal milieu (Berg, Clemente, and Colombel, 2015, p.795), in
vulnerable individuals, activates a cascade of reactions which begin with the relations of the
microorganisms and their constituents. These also comprise the dendritic cells intestinal
epithelial cells through receptors, followed by interactions of antigen-presenting cells along with
the lymphocytes, mucosal lymphocytes and vascular endothelial cells, granulocytes, and
lymphocytes, producing inflammatory intermediaries and leading to mucosal damages (Utrilla et
al., 2015, p.819). With this in mind, the investigation is ongoing in these arenas, with the final
aim of producing new therapies (Vogt et al.,2016, p.13537). No specific microbe has been
attested to cause Inflammatory Bowel Disease, notwithstanding that various microbes have been
examined as incriminating factors in the aetiopathogenesis of Inflammatory Bowel Disease.
These comprise bacteria, Escherichia coli, Chlamydia pneumonia, Listeria monocytogenes, and
Mycobacterium paratuberculosis, and cytomegalovirus, however, none of the above-said has
been connected directly with the process (Leung, Rivera, Furness, and Angus, 2016, p.421).
Nowadays further attention is paid to the lively balance between intestinal bacteria, specifically
commensal flora along with the host defense mechanism at the intestinal mucosa, as well as their
roles in the maintenance and initiation of intestinal inflammation. There is substantial proof that
deviations in the bowel microbes’ flora owing to conservational or diet dynamics are of
overriding prominence in the IBD pathogenesis. Additionally, the roles of microflora in intestinal
complaints is supported by findings that probiotics can enhance Inflammatory Bowel Disease or
antibiotics’ use could profit specific subsets of Inflammatory Bowel Disease patients. The
information has led to new beneficial strategies which target the microflora of patients with
Inflammatory Bowel Disease using synbiotics, prebiotics, probiotics agents, ranging from simple
carbohydrates to hereditarily engineered microbes with the roles of screening immunoregulatory
cytokines (Capitán‐ Cañadas et al., 1110).
Pro, Pre and antibiotics in the management of Inflammatory Bowel Disease
The accruing acquaintance that microbiota moderates gut immunological and physiology
function in Inflammatory Bowel Disease, aforementioned, has led experts to explore the
efficiency of probiotics, synbiotics, and prebiotics in the management of Inflammatory Bowel
Disease. This healing approach aims at restoring the poise of the gastrointestinal microflora to
lessen or prevent intestinal irritation. Numerous microbial strains, carbohydrates combinations,

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and their amalgamations have been tested in experimental models and scientific trials, along with
the healing manipulation of bowel microbiota.
Prevention of Inflammatory Bowel Disease
IBD is amongst the most predominant enduring gastrointestinal conditions in U.S. with a
general healthcare cost of 1.8 billion. Inflammatory Bowel Disease has no cure and patients
usually require a lifespan of care; hence effective measures to lessen hospitalization, morbidity
and surgery are precarious to improving disease free reduction and eminence of life. Research
has shown that IBD patient does not obtain preventive services with the similar care as others.
Having proper diet such as low fat foods, unprocessed and fresh foods has been proved to
prevent the occurrence of the disease. Further, one needs to be stress-free as this will help
preventing the IBD.
Symptoms of Inflammatory Bowels Disease
The symptoms of IBD mostly occur in relation to how much and where it is inflamed.
The symptoms may include vomiting, nausea, fatigue and lethargy, Diarrhoea, abnormal pain,
weight loss and passing of fresh blood in the stool. Other symptoms may include headache,
blurred vision and mouth ulcers.
Roles of Probiotics
These are living microorganisms, capable of surviving stomach acid along with the bile,
maintains viability all through the extended storage periods, and safe for human ingestion,
inducing valuable outcomes in the hosts. Numerous mechanisms of actions of probiotics relative
to treatment and prevention of Inflammatory Bowel Disease have been described, such as
antimicrobial activities and dominance of microbial development, initiation, and
immunomodulation of immune responses (Konturek, 2015, p.491), improvement of barricade
activities, as well as subdual of human T-cell propagation. Probiotics have similarly been found
to trigger their influence by using DNA as has had been displayed by an experiment using
probiotic Deoxyribonucleic acid. Derived initially from refined food, mainly dairy products, this
group comprises E. coli Nissle, Bifidobacterium species 1917and Lactobacillus species, C.
butyricum, Lactococcus lactis, VSL#3, and Saccharomyces boulardii hereditarily engineered to
discharge IL-10. An exciting new technique to what could plea a probiotic is helminths.
Lactobacillus
Lactobacilli have been utilized in several investigational models as well as clinical
experiments to scrutinize their influence on gut pathophysiology. In investigational models,
several Lactobacillus strains induce differential regulation of several genes involved in
indispensable physiological purposes such as immune reactions and weaken damage to the colon
by methotrexate and acetic acid (Laval et al., p.9). Lactobacillus casei hinders IL-6 production
within LPS-stimulated outsized intestinal lamina propria mononuclear cells and downregulates
nuclear NF-Κb translocation in in SAMP1 or Yit mice. Numerous Lactobacillus strains
upregulate intestinal MUC3 mRNA appearance (Konturek, 2015, p.491). Lactobacillus
rhamnosus was found to evoke cyclooxygenase-2 expression in human T84 colon epithelial cells

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as well as Lactobacillus paracasei ssp. paracasei ssp. paracasei overrides human T-cell
propagation (van Baarlen, Wells, and Kleerebezem, 2013, p.215). Lactobacillus GG advances
intestinal purpose by hindering of apoptosis of intestinal epithelial cells, averts colitis recurrence
in HLA-B27 transgenic rats following antibiotic management and weakens TNBS-evoked
colitis. Benefits have been shown with oral management of Lactobacillus
salivarius spp. salivarius CECT5713 within TNBS-evoked colitis. Dextran sulphate sodium
evoked colitis was weakened by everyday management of Lactobacillus GG, Lactobacillus
plantarum and Lactobacillus crispatus in several models of animals. In IL-10 knock-out pests,
Lactobacillus plantarum and Lactobacillus salivarius ssp. salivariusUCC118 have been revealed
to lessen intestinal irritation (Deriu et al.,2013, p.26).
Escherichia coli Nissle 1917
The probiotic Nissle 1917 (EcN) is a strain of E. coli that has been applied for years in
Central Europe for the prevention and management of intestinal complaints (Dupont, 2014,
p.1042). In trial condition, the E. coli Nissle 1917 downregulated the development of newly
enlisted T cells into the mucosa and confines intestinal irritation through TLR -4 and TLR-2
alleyways. DSS-evoked colitis in pests is averted by management of soluble microbial antigens
from E. coli strain nonpathogenic. Currently, Zyrek showed in vitro that EcN restored the
interrupted epithelial barriers within the colonic epithelial cell lines T84. In dual clinical
experiments E. coli Nissle 1917 was found correspondent to mesalamine at accomplishing and
maintaining UC remission for twelve-months (Kashyap et al., 2013, p.977). In preservation of
CD remission, no difference was realized in decrease between placebo and E. coli Nissle 1917,
however it should be considered that there is sturdy proof for the influence of E. coli Nissle 1917
in preservation of diminution of UC (Deriu et al.,2013, p.26).
Saccharomyces boulardii
Saccharomyces boulardii is a nonpathogenic yeast applied for management of diarrhea.
The yeast was presently shown to weaken the migration of T-helper 1 cell into the mucosa
(DuPont, 2014, p.1042), changing the cytokines’ cascades, as well as producing low-molecular-
mass element blocking NF-Κb instigation as well as IL-8 countenance. S. boulardii combination
with mesalamine was found to trigger important CD remission prolongation as well as to have
some effective outcomes in patient with active UC (Dupont, 2014, p.1042).
Clostridium butyricum
Clostridium butyricum an enterobacterium, produces in height levels of short fatty acid
that has been described to be significant in intestinal physiology. Dual studies have reported in
rodents to scrutinize the effect of this microbe. Indeed, a C. butyricum imitative was
experimented in DSS-colitis models effectively whereas Okamoto did a research on M588 strain
then demonstrated that it weakened intestinal irritation and proposed that oral C.
butyricum administration might be useful rather than butyrate purgative in the management of
UC (Birt et al., 2013, p.601).
Vsl#3
This is a probiotic preparation containing four strains of lactobacilli (casei, plantarum,
bulgaricus, and acidophilus), three bifidobacteria strains (longum, infantis, and breve) as well as
Streptococcus thermophilus which are normal constituents of the human gut microflora.

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Management of this mix to IL-10 knockout pests reduce intestinal inflammation and TNF-α
secretion as well as interferon ((IFN)-γ from the mucosa and enhances the colonic barrier
purposes (Hold et al..2014. p.1192). It has been indicated to constrain Salmonella Dublin
invasion onto T-84 cells both in in vivo and in vitro and to change linoleic acid into the anti-
inflammatory conjugated linoleic acid (Kiyono et.,2016, p.621). Non-methylated genomic DNA
removed from VSL#3 hinders TNF-α-evoked IL-8 secretions, mitogen-activated protein kinases
activations as well as NF-κBinitiation in HT-29 cells in HT-29 cell, and weakens intestinal
irritation in murine models of colitis via the TLR-9 receptors (Laval et al., p.9). This mix has
currently demonstrated roles in potentiating mucin countenance in investigational models (Birt et
al., 2013, p.601). Nevertheless, in a pest DSS colitis model the change of microflora by
supplementation with the VSL#3 didn’t repair the colonic barricade failure and didn’t heal
chronic DSS-evoked colitis (Kashyap et al., 2013, p.977).
The Microflora
The fetal intuitive is germ-free, and colonization with microbes is unrelenting contact
between the child along with its environment, depending on the delivery mode, levels of
hygiene, medication and feeding type, since differences with gut microflora conformation
happen between formula-fed infants and breast (Capitán‐ Cañadas et al., 1110). The microbial
load of the bowel comprises of “naïve” species which permanently colonize the intestine
(impartially steadied until the 4th year of life) and fleeting bacteria which are unceasingly
ingested from the peripheral milieu. Microorganisms play an enormously significant role in the
development of the gut immune systems, since it has been established in animals bred in germ-
free settings that exhibit vault hyperplasia, lack of lymphoid follicle developments as well as
other structural vagaries (Capitán‐ Cañadas et al., 1110).
Microbiological cultures in the beginning, and then nucleic acid-based techniques
“[polymerase chain reaction, 16S rRNA probing, fluorescence in situ hybridization (FISH)]”
were applied to explicate the microbial constituents of the intestinal lumens. Gastric acid,
pancreatic and bile secretions result in diminished colonization of the proximal small intestine by
most microorganisms, however density of bacteria increases in the large bowel and distal small
intestine. The faecaes and stuffing of the large bowel encompass about 1011−1012 microbial cells
for each gram of wet mass, while microorganisms from about 55-61% of the faecal weight. This
luminal bacteriological populace composes the faecal microbiota. In healthy individuals, for
phyla (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroeidetes,) as well as three groups
(Bacteroides-Prevotella group, C. leptum subgroup and Bacteroeidetes), all comprising several
species and genera) are present inside faeces. There are similarly Archaea and Fungi, however
these encompass a very small proportion of the entire quantity. Aside from the faecal microbotia,
other educations have been implemented to elucidate the individuality of microorganism present
on the mucosal superficial, signifying that they characterize a different populace that is in direct
contact with the mucosal immune system and intestinal cells of the guts. This bacterial populace
comprises of the mucosal microbiota. The aforementioned concern the microbes concern the
microorganisms, as well as other studies have clarified the microorganisms present on the
mucosal surface (Hold et al..2014. p.1192).
It has been experimented that nearly 50% of microorganisms traced with molecular
techniques couldn’t be cultured within the lab using standard systems. This discloses the
problems met in trying to classify each microorganisms making up the microflora. The mucus

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presence that is of great significance in the nesting of the commensal vegetation has to be
considered in the course of ascertaining microorganisms. As was pointed out by Tannock, DNA-
based methods expose only who could have been present. Additionally, RNA-based methods
identify microorganisms which are metabolically vigorous at the experimentation time.
Consequently, the usage of the function-exposing methods such as proteomics and
transcriptomics is essential so as to reveal the exact microflora’s role (Hold et al..2014. p.1192).
In addition, it has been proposed that, apart from distinguishing the presence of a definite species
of microbes, it is essential to distinguish its scrupulous position in the substructure of the
microflora, hence making known the word ‘spatial organization of the mucosal flora’
The roles of Microflora in Inflammatory Bowel Disease
Experimental and clinical evidences have led to the supposition that microbes generally
and commensal microflora more exactly play a significant role in the perpetuation and onset of
Inflammatory Bowel Disease. In 1985 Harper showed that reinstating the small bowel sewage of
the patient with CD managed with riven colostomy, instead of its germ-free ultra-filtrate (which
contain non microbial cells or other inordinate particles), into the “hibernating” colon made
inflammation of the region. Additionally, alteration of the stream within CD lessens gut
inflammation and triggers healing within the debarred part of the bowel, while pouchits doesn’t
happen afore ileostomy takedown. Another remark that stalwartly supports this philosophy is the
prevalence of Inflammatory Bowel Disease abrasions in regions of the greatest microbial
exposure, this is incurable ileum, ileal and colon purses. Antibiotics have been confirmed of
some worth in managing IBD although there is proof of action instead of decently antimicrobial,
as validated by experimental model of the ciprofloxacin and inflammation (Moreno et al., 2014,
p.187).
The role of microorganisms in Inflammatory Bowel Disease is strongly validated by
sterile animal experimentations. Genetically engineered (gene knock-out and transgenic) pests
display deadly intestinal irritation under standard lab conditions, however failed to do so when
raised in a sterile milieu and chemically induced colitis with (TNBS); trinitrobenzene sulphonic
acid happens in normal pests, however not in rats formerly treated with antibiotic. Furthermore,
adding diverse species of microbes or diverse LPS parts from the similar strain in transgenic
animals comprises diverse lymphocytes subpopulation initiation. The findings suggest that not
every microorganism triggers the similar antigenic stimulation that means that management with
probiotic strains primarily depends on the chosen strain (Huttenhower, Kostic, and Xavier, 2014,
p. 854).
The faecal and mucosal microbiota has been found to vary between fit subjects and
patients Inflammatory Bowel Disease. Even though fallouts are differing about the overriding
species in every case (Owaga et al., 2015, p. 20858), one might say that there are distinctive
characteristics which distinguish the microbiota inhabiting the tract of patient with IBD in
contrast with that of health individuals (Huttenhower, Kostic, and Xavier, 2014, p. 854). There is
greater biodiversity of species in fit subjects, as well as overriding species include nearly ninety-
percent of the entire microbial populace, while in IBD patient, biodiversity is lower and there’s
great proportion (nearly 30%) of “unusual species.” It has similarly been shown that healthy
people are pigeonholed by a greater Firmicutes percentage (Nami, Haghshenas, and Yari
Khosroushahi, 2017, p.563)
Roles of Prebiotics

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These are complex carbohydrates that stimulate the development of specific species of the
microflora of the host leading to bettered enteric purpose (Salazar et al., 2016, p.1440). These
complex food elements primarily act by increasing the populace of definite microbes and hence
quantitatively changing the microflora. As soon as they reach the colon, they are fermented by
anaerobic microbes, producing short-chain fatty acids along with the gas (Carbon-dioxide and
water). In the effect, intraluminal pH drips, favoring the rise of nonpathogenic E. coli,
Lactobacilli and Bifidobacteria as well as reducing Bifidobacteria. The fermentation of
C12H12O11 similarly leads to the production of butyrate, propionic and acetic acids, which are
involved in numerous colon-specific as well as systematic paths (Shetty et al., 2017, p.199).
Acetate is utilized as cell fuel and propionic acid is included in cholesterol production. Of these,
butyrate is of great significance to the absorption of the colonocyte. It has similarly been
established that butyrate exerts anti-inflammatory action, by in vitro decreasing the countenance
of TNF-α-interrelated cytokines and upregulating IL-10 in pests, perhaps by reticence of the
nuclear NF-κB translocation (Minamoto et al., 2015, p.47). Butyrate purgatives have been
applied with feat in UC, however the need for incessant management confines its use. The most
frequently used prebiotics in investigational models and medical trials are insulin, oligofructose,
lactosucrose, lactulose, milk-oligosaccharides, germinated barley foodstuff, and psyllium
(Matijašić et al.,2016, p.578).
Lactulose
Lactulose weakens irritation in IL-10 knockout pests. It has similarly lessened
myeloperoxidase action, leukotriene B fabrication, TNF-α and upsurges Lactobacilli and
Bifidobacteria, when controlled for two weeks prior to stimulation of TNBS colitis in pests. It
has equally validated a dose-department valuable in DSS-evoked colitis. In an experimental
study, oral lactose had no valuable effects in patients of Inflammatory Bowel Disease as regards
experimental action, endoscopic score or immunohistochemical parameters, however improved
the life quality. Nonetheless, its side-effect majorly diarrhoea confines its use in medicinal trials
Lactosucrose
This is a water-soluble fibre that is displayed to upsurge the proportion of Bifidobacteria
as well as the entire amount of microorganisms healthy subjects, however with no impact on
SCFA. In a research by Teramoto, management of lactosucrose for two weeks in Inflammatory
Bowel Disease patients led to a rise in Bifidobacteria and a reduction in Bacteroidaceae, however
in spite of these favorable effects, lactosucrose hasn’t been further examined.
Oligofructose and inulin
These are both comprises of numerous saccharide units as well as have analogous
purposes in the bowel that motivate development and action of Bifidobacteria and Lactobacilli.
Their mixture averts increase of colitis in HLA-B27 transgenic pests. Inulin weakens irritation
and lessens marker of inflammation in DSS-evoked colitis, resulting also to the rise of lactic acid
microbes and drop in PH. Licht have testified that inulin and oligofructose feeding (distinctly) to
mice led to a grander proportion of lactic acid microorganisms and greater butyrate heights.
Oligofructose and Inulin given together, had analogous fallouts in heathy individuals. In a
medical experiment, patients with a deterioration of insignificant to moderate UC established
mesalazine in amalgamation with oligofructose-enhanced placebo or inulin. Oligofructose-
enhanced inulin is well allowed and linked with an early reduction in faecal calprotectin.

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Fructo- and milk-oligosaccharides
Fructo-oligosaccharides have been established to weaken TNBS-evoked colitis in mice,
encouraging the development of valuable lactic acid and increasing levels of butyrate, however
not DSS-colitis in pests. The mixture of inulin and fructo-oligosaccharides, uniting the beneficial
impact, the primary in the microflora modulation as well as of the succeeding in increasing levels
of butyrate, has been reported to weaken histological and macroscopic irritation in HLA-AB27
transgenic pests. Milk of the goat; oligosaccharides is fed to DSS-colitis pests had a useful effect
in preservation of their mass, with diminished colonic myeloperoxidase action, warmer scientific
symptoms as well as augmented MUC-3 likened with control and TNBS-colitis pests. In a
current study Vos had shown that nutritional supplementation of oligosaccharides enriched Th1-
dependent inoculation rejoinders in pests. In open label study by Lindsay in 15 CD patients,
fructo-oligosaccharides were publicized to raise IL-10 levels countenance within dendritic cell,
with a rise of Bifidobacteria (Zevin, McKinnon, Burgener, and Klatt, 2016, p.190)
Synbiotics
Symbiotic is combined products of pre-and probiotics. The aforementioned valuable
effects of both prebiotics and probiotics in investigational models and medical trials have
resulted to scientist to the thought of coalescing them in a novel healing scheme termed
synbiotic. As already shown (Martín et al., 2015, p.67), every prebiotic and probiotic has
distinctive features, acting in its individual way in moderating the microflora, and it’s hence
abstracted that there were several amalgamations to be studied. Furthermore, the multifaceted
association and purpose of the intestinal microflora doesn’t make sure that amalgamations that is
expected to action synergistically, founded on the fact that every constituent of the mix has a
detailed role, would do so. Nonetheless, it’s essential to study these management selections, as
the mix of managements will expectantly lead to suppler healing schemes, enhancing
acquiescence of patients and reducing costs (Shetty et al., 2017, p.199).
Treatment of Inflammatory Bowel Disease
Trivial inflammatory bowel disease
Management of trivial IBD requires topical management depending on the number of
symptoms. Less than three stools daily require a corticosteroid enema which is placed within the
rectum as a preservation enema to help reducing the symptoms. Further, a number of diverse
medications are recommended depending on symptoms such as antibiotics; used to manage
Crohn’s disease as well as its complications (abscesses and fistula), however are commonly not
applied in ulcerative colitis. Another prescription is Aminosalicylates which comprises of
olsalazine, mesalazine and sulfasalazine are used for moderate to mild crohn’s disease and any
ulcerative colitis. Glucocorticoids such as budesonide, prednisolone and hydrocortisone, are
used to cure and ulcerative colitis and Crohn's disease since their anti-inflammatory properties
act very rapidly to lessen symptoms
Conclusion
Throughout current decades, prebiotics and probiotics have been utilized an outsized
number of investigational models of clinical and colitis trials. Experimental studies in vivo and
in vitro have offered good proof that microbial and bacterial constituents are connected in the
pathogenic mechanism of gut pathophysiology along with that duodenal microflora plays an
essential role in the IBD pathogenesis. These studies have assisted in identifying the vicissitudes

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of the luminal setting and mucosal of bowel and to comprehend the interaction of these
microorganisms with the central mucosal immune systems within the gut. Nonetheless, a better
comprehension of this environment is required to find out which microbial strain or prebiotic
will be the idea management for a given bowel complaint. Conversely, experimental trials have
provided contradictory results hence far. It’s essential to cite the more philosophical medical
effect of this treatment in UC remissions and preventions of pouchitis within CD, while welfares
are restricted in CD fallouts must be collected as for nongastrointestinal signs of IBD.
pharmabiotics agents have shown lack of poisonousness when they appear to be an excellent
resolution to patients who were unenthusiastic to take medications (a very significant element,
particularly on situations such as IBD, where management is extended and hard to deal with),
prebiotics and probiotics are, not drugs but "nature products.’ Pre-and probiotics have proven
their valuable effect in healthy subjects, both clinically and experimentally, to an equivalent, in
our view a greater magnitude than in patients of IBD. The result from medical studies has shown
that these rehabilitations are equal to those conventionally used, besides, in a few cases, good at
maintaining remission induced by common remedies to examine their potential as preventive
means apart from IBD remedy.

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