Introduction: substrate availability dictate the environmental conditions. This

Introduction: Based on a meta-analysis covering several
large Sanger-sequencing studies of human gut samples from different populations
the most numerically dominant phyla within the intestinal microbial community
are the firmicutes and bacteroidetes that comprise more than 90% of the total
bacteria. The levels and diversity of the microbial community within the
gastrointestinal tract can differ according to the location as different
physicochemical properties and substrate availability dictate the environmental
conditions. This enormous microbial community has been estimated to be in the
region of 1014 microorganisms, the collective gene set of which is termed the
“microbiome” and is thought to contain approximately 100 times the number of
genes in the human genome (Backhed et al. The distal large intestine is the
area of highest colonization with more than 500 differ- ent species (with some
estimates suggesting up to 1,000 species) with potentially up to 100 billion
microbial inhabitants (Boyle and Tang 2006. Other bacterial phyla that have
been isolated include also actinobacteria, gammaproteobacteria, verrucomicrobia,
and betaproteobacteria (Hamady and Knight 2009. The total area of the mucosal
surface of the human gastrointestinal tract is 300 m2 which makes it the
largest surface area in the body that inter- acts with the external environment
(Bjorksten 2006. This has led to collaborative research projects the largest of
which is probably the Human Microbiome Project, which is a worldwide strategy
aiming to further delineate the extent of both human and microbial diversity.
For example, all humans possess several hundred species within each genus in
their gut, however the foremost species within that genus will differ
considerably between individuals (Simon and Gorbach 1984. More recently, use of
a culture-independent approach has revealed the complexity of the resident
microbial communities; this was enabled by use of oligonucleotide probes based
on 16S rRNA gene sequences. Further classification of bacteria based upon
phylogenetic comparisons of the 16S rRNA sequences has been possible using
qualitative and quantitative techniques. For example, PCR reactions and
fluorescent in situ hybridization (FISH) use primers and probes respectively
which tar- get bacteria based on their 16S rRNA sequences. It is estimated that
these specific probes have enabled identification of up to 80% of the total
microbial diversity within the intestinal. Differences in microbiota
composition have been found between infants born in different countries and
raised with different diets and even between hospital wards (Adlerberth et al.
Probably the most important factors in determining the initial colonization
pattern are the type of delivery at birth (either vaginal or caesarean section)
and the initial diet (whether the newborn is fed mother’s milk or infant
formula. The composition of the adult microbiota is thought to be more stable,
however acute effects can disrupt this homeostasis for example, during
antibiotic treatment, after gastrointestinal surgery, exposure to radiation,
and in some infectious. It can be thought of as a ‘microbial organ’ as the
processes performed by this diverse population are extensive; it can
communicate with itself (bacteria: bacteria) and with the host (bacteria:
human. The presence of the gut microbiota has influenced human evolution in
that the human host cannot perform certain vital intestinal functions without
them. Maintenance of homeostasis is an interactive process between the bacteria
and host epithelia which influences both intestinal physiology and the
derivation and distribution of energy. Germ-free animal models have provided
useful insights into the roles of the microbiota and the extent of interaction.
The major source of energy from colonic fermentation is from carbohydrates,
which include large polysaccharides (such as plant derived pectin,
hemicellulose, cellulose, gums, and resistant starch) and also less complex
carbohydrates such as oligosaccharides and non-absorbed alcohols and sugars (Cummings
et al. This is an example of a symbiotic relationship as the human host bene-
fits from a wide array of microbial enzymes which are outside the host’s own
biochemical repertoire. This provides the host with a source of energy from the
food ingested and also to the micro flora which in turn is used to sustain the
microbial community. In contrast, the left side of the colon has less
carbohydrate fermentation, the pH is less acidic, and it is associated with an
increase in proteolysis which has been linked to the production of harmful
nitrogenous products, which accounts for the recommendation to eat a
carbohydrate and fiber enriched diet (Guarner and Malagelada 2003. Fermentation
activity differs according to area within the gut, the most metabolically
active area is the caecum and right colon, consequently this is an area of
rapid bacterial growth, low pH (5–6) and rapid generation of SCFA as a result
of carbohydrate fermentation (Cummings et al. Fermentation can also occur with
noncarbohydrate substrates, therefore proteolytic fermentation (of proteins and
peptides) also generates potentially damaging compounds such as ammonia,
amines, and phenolic compounds (Macfarlane et al. The main fermentation end
products are short chain fatty acids (SCFA) which are small organic molecules
absorbed.

 

THE GUT MICROBIOTA AND AUGMENTATION OF
HOST DEFENSE: Anti-pathogenic
Activity: Bacteriocins A useful feature of probiotic bacteria is the ability of
some strains to demonstrate a specific inhibitory activity towards other
organisms which can sometimes be against pathogenic strains. It is thought that
the gut microbiota can positively influence the immune system by maintaining a
sufficiently stimulated mucosal immune system, which can react quickly to an
environmental antigen but which can also differentiate between pathogens and
com- mensal organisms, therefore not promoting an immune response un-
necessarily. Bacteriocinogenic lactic acid bacteria (LAB) strains that are
active against food spoilage or pathogens are still the subject of research
interest as they represent a source of natural food preservatives, are
generally regarded as safe, and are well tolerated. More recently, this has
been redefined as “extracellularly released primary or modified products of
bacterial ribosomal synthesis, which can have a relatively narrow spectrum of
bactericidal activity, characterized by inclusion of at least some strains of
the same species as the producer bacterium and against which the producer
strain has some mechanism(s) of self protection,” (Jack et al. This strategy
makes it more difficult for pathogens to interact with epithelial cells; this
means the pathogen can be competitively excluded from the epithelial surface
which can prevent adhesion of the pathogen and possibly subsequent infection
processes. It can also be more specific due to production of bacteriocins which
are peptides defined as “antimicrobial proteins that are active against
bacteria, usually active against the producer organism and most often produced
by Gram positive bacteria,” (Tagg 1976. The current model defined by
Klaenhammer (1993) proposes four main classes; lantibiotics, nonlantibiotic
peptides, nonlantibiotic large heat labile proteins, and complex bacteriocins
(that contain essential lipid/protein residues in addition to protein.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

PROBIOTICS: Bifidobacteria and Lactobacilli
Probiotics are most commonly found within the genera Lactobacillus and
Bifidobacterium although exceptions do occur. The number of recognized
organisms classified as Lactobacilli has in- creased, for example in 1984 there
were 44 reported Lactobacillus species, however in 2003 this reached 88 and in
2007 reached 135 species (Bernardeau et al. This enzyme is also used as a
taxonomic tool to identify Bifidobacterium species; however, it cannot be used
to discriminate between species (Lauer and Kandler 1983. Although sharing some
phenotypic features with lactic acid bacteria, the genus Bifidobacterium is
actually related to the Actinomycetes. Another common probiotic group includes
the bifidobacteria, the common human group isolates include B. This not only
reflects the diversity of the Lac- tobacillus genus but also that with the
current progression of molecular techniques maybe other genera will also be
revised. Lactobacilli comprise a diverse group of Gram positive bacteria,
typical features include: nonsporulation, catalase negative, devoid of
cytochromes, an- aerobic (sometimes aerotolerant) and acid tolerant cocci or
rods which produce lactic acid as a major fermentation end product (Axelsson
1998. Lactobacilli contain species with 33–53% chromosomal G+C content and have
been classified according to phenotypic characteristics, fermentation/metabolic.
A number of reasons could be influential including lack of standardization with
study protocols or therapies (including antibiotics and probiotics used.
Therefore, probiotics are finding applications alongside modern medicine as it
is thought that the incidence or severity of associated infections can be
reduced during probiotic co- administration. boulardii and Lactobacillus
species, however further studies were necessary to compensate for a lack of
placebo design in studies already completed (Cremonini et al. Clostridium
Difficile Within the healthy population Clostridium difficile is considered to
be present at approximately 3%, however during hospital admissions it can rise
to between 15% and 35%, which has recently been highlighted in the media.
difficile is an opportunistic pathogen and recent figures in the United States
show it is the most common cause of nosocomial diarrhea with 15–25% of adult
patients suffering from it (Bartlett and Gerding, 2008. However, patients with
a prior episode showed significant inhibition of reoccurrence (McFar- land et
al. Diarrhea is a common side effect of the administration of antimicrobial
therapy such as antibiotic administration. Probiotics have been used as an
antibiotic adjunct, for example S. 2009) however despite further research there
appears to be no definitive conclusions regarding probiotic efficiacy as an
adjuvant therapy and in preventing patient relapse. boulardii preparation, for
example 193 patients taking ?-lactam antibiotics were divided into two groups. Traveler’s Diarrhea with increasing
worldwide travel, traveler’s diarrhea is a commonly reported complaint and it
is estimated to affect 20–50% of travelers from industrialized countries when
visiting tropical or semitropical countries (Fric 2002. There are several
postulated antiviral mechanisms including competitive inhibition of the virus
from binding to the epithelial surface, general immune enhancement (thus more
efficient virus inactivation), increased mucin gene expression (as glycosylated
mucins trap rotavirus), and production of antiviral sub- stances (found in some
probiotic supernatants. Acute childhood diarrhea worldwide is most commonly
caused by rotavirus and can be an important con- tributor to infant mortality,
thus probiotics have been used to both treat and prevent the disease. A study
of 100 children admitted to a hospital with acute viral diarrhea demonstrated a
reduced duration of disease when the treatment group received Lactobacillus GG
therapy compared to a control, which received rehydration salts alone (Guarino
et al. In fact, they con- cluded that Lactobacillus GG was effective at
reducing the symptoms of not only rotavirus-positive subjects but also those
that had diarrhea not caused by rotavirus. Viral Diarrhea A number of studies
have reported the efficacy of Lactobacillus GG in terms of its antiviral
effects. Although Lactobacillus GG is the most commonly reported probiotic in
this research, others have been used such as Bifidobacterium lactis BB-12 and
Lactobacillus reuteri SD2222 (Guarino et al. Several studies suggest that
travelers can expect a 20–50% reduction in the risk of illness if Lactobacillus
GG is con- sumed when entering an area of high risk (Hilton et al. An even
larger study was conducted with 287 children with viral diarrhea. The treatment
group received oral rehydration salts (standard therapy) with addition of
Lactobacillus GG; the control group received oral rehydration salts with no
live bacteria.
Probiotics have been
shown to boost host immune status via stimulation of specific and nonspecific
immune pathways involving modification and regulation of humoral, cellular, and
nonspecific immunity (Cross et al. In summary, the immunomodulation process is
complex and dependent on both host and the probiotic strain and could be
influenced by host immune status, amount of probiotic administered, duration of
administration, and strain viability. Inflammatory Conditions Inflammatory
bowel disease (IBD) is a term for immune-mediated conditions which result in
chronic intestinal inflammation and are not attributable to specific pathogens.
Some reported positive in vivo effects of probiotics including amplified mucus
production, macrophage activation by Lactobacilli signaling, stimulation of
secretory IgA, decreased proinflammatory cytokine production, and increased
peripheral immunoglobulin production. Probiotics can enhance barrier function
and stimulate specific and nonspecific immune responses in the host, therefore
could theoretically decrease the adherence of pathogens (and consequent
invasion. Allergic diseases such as asthma, atopic eczema, allergies, allergic
rhinitis, coupled with inflammatory bowel disorders such as Crohn’s disease,
chronic inflammatory bowel disease, and ulcerative colitis have all been linked
to impaired gut-barrier dysfunction (Sanderson and Walker 1993. The best clinically
documented effects of probiotics have been in treatment of acute diarrhea but
have been also documented for immune linked responses, for example in gut
mucosal normalization and down-regulation of hypersensitivity reactions
(Isolauri et al. Immunomodulation Inflammatory and allergic conditions are
major problems to world health; they are thought to arise from a combination of
factors including genetics and immunological disturbance (allergens and
antigens. In animal models, age related decreased cytokine production has been
shown to be reversed with probiotic supplementation (Muscettola et al. Recent
studies have shown also the ability of probiotics to modulate the immune system
in the elderly, including activation of natural killer cells (Gill et al. A meta- analysis using data obtained from
20 trials (with n = 1,404 subjects) concluded that probiotics did indeed
provide some quantifiable benefit in terms of overall symptom reduction when
compared to placebo, however comparison was hampered for several reasons
including pro- biotic species used, administration period, study sample size,
and dos- age (McFarland and Dublin 2008. One study found no beneficial effect
of Lactobacillus GG on IBS symptoms in infants when compared to the control
(Bausserman and Michail 2005. The first study found that patients successfully
stayed in remission during the study (Cashman and Shanahan 2003. The second
study showed that the probiotics could have beneficial effects during periods
of active UC (Kato et al. Recent studies have compared the relapse rates of UC
sufferers with two different treatments in a double-dummy blind double trial
where patients received either mesalazine (3 × 500 mg/day) or E. Various
studies have been conducted which look at easing symptoms or preventing
reoccurrence of symptoms (Halpern et al. Cocktails of probiotics have been used
and found to be effective in maintenance of remission. Studies in
experimentally-induced animal models of colitis have shown beneficial effects
of probiotics in terms of reduction of intestinal

PREBIOTICS: Although prebiotic and probiotic
approaches are likely to share common mechanisms of action since their effect
is impacted through the increase of beneficial colonic bacteria in both cases,
they differ in specific effects on microbiota composition and host metabolism.
Selective Stimulation of Beneficial Bacteria In the GI tract, prebiotics
selectively stimulate indigenous beneficial bacteria such as bifidobacteria and
lactobacilli (Reid et al. Although the Prebiotics 35 effect of certain
prebiotic-like inulin-type fructans on Bifidobacterium population is well
documented, in vivo studies usually tend to consider the bifidobacterial
community as a whole, ignoring interspecies differences (Macfarlane et al.
Prebiotic Effects The effects of prebiotics have been primarily directed toward
the colon, but an increased amount of evidence demonstrates that prebiotics
exert their effect beyond the GI tract (Lenoir-Wijnkoop et al. Prebiotic
Effects The effects of prebiotics have been primarily directed toward the
colon, but an increased amount of evidence demonstrates that prebiotics exert
their effect beyond the GI tract (Lenoir-Wijnkoop et al. The different
mechanisms of prebiotic action are complex and have been summarized in Figure
Selective Stimulation of Beneficial Bacteria. This definition has recently been
updated as follows: ‘a prebiotic is a selectively fermented ingredient that
results in specific changes in the composition and/or activity of the gastrointestinal
microbiota, thus conferring benefit(s) upon host health’ (Gibson et al.
Products of prebiotic fermentation by lactobacilli and bifidobacteria, such as
lactic and acetic acid, can also be subsequently degraded by other members of
the gut (Duncan et al. Prebiotics have been originally defined as
‘non-digestible food ingredients that beneficially affect the host by
selectively stimulating the growth and/or activity of one or a limited number
of bacteria in the colon, and thus improve host health’ (Gibson and Roberfroid
1995. This may impact their competition with other commensals. Impact of Prebiotics on Short Chain Fatty
Acid Production SCFAs (acetate, propionate, and butyrate) are the main products
of prebiotic fermentation in the gut. Close relationships between microbes
usually explain an increase in butyrate production, often seen in the presence
of prebiotics, despite the fact that primary prebiotic utilizers (lactic acid
bacteria) fail to produce this compound. SCFAs may be important in host
metabolism as these compounds provide energy to the host. Regulation of Host
Metabolism Metabolomic studies that measure the impact of a single prebiotic
have started to reveal the complexity of the changes induced by its ingestion.
Using a multicompartmental modelling approach with metabolic signatures from 10
tissue/fluid compartments to assess the effects of 5 g/day of galtactosyloligosaccharides,
a significant reduction of lipogenesis, triacylglycerol incorporation into
lipoproteins and triglyceride concentration in the liver and the kidney could
be measured in mice (Martin et al. These different mechanisms illustrate the
complexity of regulation of the host metabolism by prebiotics. This effect may
be partially due to the interaction of inulin type fructans with the Fok1 gene,
a genetic modifier of calcium absorption, as well as due to the acidic
environment caused by the production of SCFA, which may increase the solubility
of minerals and thus enhance their absorption (Abrams et al. MineralAbsorption
The addition of prebiotics in food may offer other benefits by improving host
absorption of minerals (like calcium or magnesium. Crude fractions of chicory
(a source of inulin) have shown improved bone parameters relative to native or
reformulated inulin in rats, suggesting possible synergies between inulin-type
fructans and other nutrients (Demigne et al. Re- cent advances in this field
show that inulin-type fructans enhanced calcium absorption primarily via the
colonic mucosa in humans (Abrams et al. Antiadhesive Prebiotics An extension to
the prebiotic concept is the use of oligosaccharides that selectively prevent
adhesion of certain bacterial species by mimicking their binding sites. While
this field of research is intriguing, no human trials have examined prebiotics
in pro- phylactic studies and it warrants further investigation.