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Alterations in the bowel flora and its activities are now believed to be contributing factors to many chronic and degenerative diseases. Irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, and ankylosing spondylitis have all been linked to alterations in the intestinal microflora. The intestinal dysbiosis hypothesis suggests a number of factors associated with modern Western living have a detrimental impact on the microflora of the gastrointestinal tract. Factors such as antibiotics, psychological and physical stress, and certain dietary components have been found to contribute to intestinal dysbiosis. If these causes can be eliminated or at least attenuated then treatments aimed at manipulating the microflora may be more successful
Page 180 Alternative Medicine Review
Volume 9, Number 2 2004
Intestinal Dysbiosis Review
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Jason A Hawrelak, BNat (Hons) – PhD Candidate in the
field of intestinal micro-ecology, Southern Cross
University’s School of Natural and Complementary
Medicine and the Australian Centre for Complementary
Medicine Education and Research.
Correspondence address: School of Natural and
Complementary Medicine, Southern Cross University, PO
Box 157, Lismore NSW, Australia 2480
Stephen P Myers, PhD, BMed, ND – Professor and Head of
the Australian Centre for Complementary Medicine
Education and Research.
Alterations in the bowel flora and its activities
are now believed to be contributing factors to
many chronic and degenerative diseases.
Irritable bowel syndrome, inflammatory bowel
disease, rheumatoid arthritis, and ankylosing
spondylitis have all been linked to alterations
in the intestinal microflora. The intestinal
dysbiosis hypothesis suggests a number of
factors associated with modern Western living
have a detrimental impact on the microflora of
the gastrointestinal tract. Factors such as
antibiotics, psychological and physical stress,
and certain dietary components have been
found to contribute to intestinal dysbiosis. If
these causes can be eliminated or at least
attenuated then treatments aimed at
manipulating the microflora may be more
(Altern Med Rev 2004;9(2):180-197)
The gastrointestinal tract (GIT) is one of
the largest interfaces between the outside world
and the human internal environment. From mouth
to anus, it forms a nine-meter long tube, consti-
tuting the body’s second largest surface area and
estimated to cover approximately 250-400 m
Over a normal lifetime, approximately 60 tons of
food will pass through the GIT.
Food is obviously
extremely important for well-being, but its pas-
sage through the GIT can also constitute a threat
to health. While the GIT functions to digest and
absorb nutrients, food also provides exposure to
dietary antigens, viable microorganisms, and bac-
terial products. The intestinal mucosa plays a dual
The Causes of Intestinal Dysbiosis:
A Review
Jason A. Hawrelak, BNat (Hons), PhD Candidate and
Stephen P. Myers, PhD, BMed, ND
role in both excluding these macromolecules and
microbes from the systemic circulation and ab-
sorbing crucial nutrients.
As mentioned above, the mucosa is ex-
posed to bacterial products – endotoxins,
gen sulphide,
phenols, ammonia, and indoles
that can have detrimental effects on both mucosal
and host health.
The presence of many of these
toxic metabolites is directly dependent on the type
of fermentation that occurs in the bowel. In turn,
this fermentation is dependent on the type of bac-
teria present in the bowel, as well as the substrates
available for fermentation. Diets high in protein
and sulfate (derived primarily from food addi-
have been shown to contribute greatly to
the production of these potentially toxic products.
The production and absorption of toxic metabo-
lites is referred to as bowel toxemia.
The bowel toxemia theory has historical
roots extending as far back as Hippocrates. In 400
B.C. he stated that, “...death sits in the bowels...”
and “...bad digestion is the root of all evil....”
modern proponents of the bowel toxemia theory
have included naturopath Louis Kuhne in the late
nineteenth century,
as well as naturopath Henry
and Nobel prize laureate Elie
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Alternative Medicine Review
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Review Intestinal Dysbiosis
Metchnikoff in the early twentieth century.
Kuhne proposed that excess food intake, or the
intake of the wrong types of food, resulted in the
production of intestinal toxins. Fermentation of
these toxins resulted in increased growth of bac-
teria within the bowel and, subsequently, disease.
He believed a predominantly vegetarian and
mostly raw diet would prevent build-up of intes-
tinal toxins and, hence, would prevent and even
cure disease.
Only a few years later, Metchnikoff popu-
larized the idea that fermented milk products could
beneficially alter the microflora of the GIT. He
believed many diseases, and even aging itself,
were caused by putrefaction of protein in the bowel
by intestinal bacteria. Lactic acid-producing bac-
teria were thought to inhibit the growth of putre-
factive bacteria in the intestines. Thus, yogurt con-
sumption was recommended to correct this “au-
tointoxication” and improve composition of the
The bowel toxemia theories eventually
evolved into the intestinal dysbiosis hypothesis.
The term “dysbiosis” was originally coined by
Metchnikoff to describe altered pathogenic bac-
teria in the gut.
Dysbiosis has been defined by
others as “...qualitative and quantitative changes
in the intestinal flora, their metabolic activity and
their local distribution.”
Thus dysbiosis is a state
in which the microbiota produces harmful effects
via: (1) qualitative and quantitative changes in the
intestinal flora itself; (2) changes in their meta-
bolic activities; and (3) changes in their local dis-
tribution. The dysbiosis hypothesis states that the
modern diet and lifestyle, as well as the use of
antibiotics, have led to the disruption of the nor-
mal intestinal microflora. These factors result in
alterations in bacterial metabolism, as well as the
overgrowth of potentially pathogenic microorgan-
isms. It is believed the growth of these bacteria in
the intestines results in the release of potentially
toxic products that play a role in many chronic
and degenerative diseases.
There is a growing body of evidence that
substantiates and clarifies the dysbiosis theory.
Altered bowel flora is now believed to play a role
in myriad disease conditions, including GIT dis-
orders like irritable bowel syndrome (IBS)
inflammatory bowel disease (IBD),
as well as
more systemic conditions such as rheumatoid ar-
thritis (RA)
and ankylosing spondylitis.
knowledge of the factors that can cause detrimen-
tal changes to the microflora is becoming increas-
ingly important to the clinician.
The Importance of Normal GIT
The microflora of the gastrointestinal tract
represents an ecosystem of the highest complex-
The microflora is believed to be composed
of over 50 genera of bacteria
accounting for over
500 different species.
The adult human GIT is
estimated to contain 10
viable microorganisms,
which is 10 times the number of eukaryotic cells
found within the human body.
Some researchers
have called this microbial population the “mi-
crobe” organ – an organ similar in size to the liver
(1-1.5 kg in weight).
Indeed, this microbe organ
is now recognized as rivaling the liver in the num-
ber of biochemical transformations and reactions
in which it participates.
The microflora plays many critical roles
in the body; thus, there are many areas of host
health that can be compromised when the micro-
flora is drastically altered. The GIT microflora is
involved in stimulation of the immune system,
synthesis of vitamins (B group and K), enhance-
ment of GIT motility and function, digestion and
nutrient absorption, inhibition of pathogens (colo-
nization resistance), metabolism of plant com-
pounds/drugs, and production of short-chain fatty
acids (SCFAs) and polyamines.
Factors that Can Alter the GIT
Many factors can harm the beneficial
members of the GIT flora, including antibiotic use,
psychological and physical stress, radiation, al-
tered GIT peristalsis, and dietary changes. This
review will focus exclusively on the interactions
of antibiotics, stress, and diet with the gut flora.
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Table 1a. The Effects of Some Selected Antibiotics on GIT Microflora
clavulanic acid
of resistant
Days to
of flora (post-
not stated
not stated
not stated
not stated
not stated
not stated
not stated
not stated
in Lactobacilli
and Bifidus; in
production of
in Lactobacilli
and Bifidus
in Candida
in Lactobacilli
No significant
change in
Bifidus or
in Bifidus;
in C. difficile
in Lactobacilli
and Bifidus
in Bifidus; in
C. difficile
in Lactobacilli
and Bifidus; in
Candida and
Impact on
An overview of some of the research investigating the effects of selected antibiotics on the GIT microflora. ↓↓ = strong
suppression (> 4 log 10 CFU/g feces); = mild to moderate suppression (2-4 log 10 CFU/g feces); = increase in number of
organisms during therapy; - = no significant change; = decrease; + = positive result; Bifidus= Bifidobacterium spp.
Alternative Medicine Review
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Table 1b. The Effects of Some Selected Antibiotics on GIT Microflora
of resistant
Days to
of flora (post-
not stated
not stated
not stated
not stated
not stated
not stated
not stated
not stated
in Lactobacilli
and Bifidus; in
C. difficile and
Candida; 70% of
drug excreted in
in Lactobacilli;
in C. difficile
in Candida and
in Lactobacilli
in Lactobacilli
and Bifidus; in
C. difficile and
in Lactobacilli
No effect on
Lactobacilli; in
Citrobacter spp.
and Proteus
in Bifidus; in
Candida; 30% of
drug excreted in
No in yeast
in C. difficile
Impact on
An overview of some of the research investigating the effects of selected antibiotics on the GIT microflora. ↓↓ = strong
suppression (> 4 log 10 CFU/g feces); = mild to moderate suppression (2-4 log 10 CFU/g feces); = increase in number of
organisms during therapy; - = no significant change; = decrease; + = positive result; Bifidus= Bifidobacterium spp.
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Table 1c. The Effects of Some Selected Antibiotics on GIT Microflora
of resistant
Days to
of flora (post-
not stated
not stated
not stated
in yeast
colonization; no
effect on Bifidus
or Clostridia
10% of drug
excreted in bile;
production of
SCFAs; in
Bifidus and
No effect on
in Candida
No significant
change in
Lactobacilli or
Bifidus; in yeast
production of
in Lactobacilli
and Bifidus
No significant
change in
yeasts, Bifidus, or
in Lactobacilli
and Bifidus; in
Candida and
C. difficile
in Lactobacilli
and Bifidus; in
Impact on
An overview of some of the research investigating the effects of selected antibiotics on the GIT microflora. ↓↓ = strong
suppression (> 4 log 10 CFU/g feces); = mild to moderate suppression (2-4 log 10 CFU/g feces); = increase in number of
organisms during therapy; - = no significant change; = decrease; + = positive result; Bifidus= Bifidobacterium spp.
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The Impact of Antibiotics on GIT
Antibiotic use is the most common and
significant cause of major alterations in normal
GIT microbiota.
The potential for an
antimicrobial agent to influence gut microflora is
related to its spectrum of activity,
pharmacokinetics, dosage,
and length of
Regarding the spectrum of
activity, an antimicrobial agent active against both
gram-positive and -negative organisms will have
a greater impact on the intestinal flora.
Table 1d. The Effects of Some Selected Antibiotics on GIT Microflora
Clavulanic acid
of resistant
Days to
of flora (post-
not stated
not stated
not stated
not stated
not stated
not stated
not stated
not stated
not stated
No effect on
No significant
change in Bifidus;
larger doses
in Candida;
no change in
Bifidus or
in Lactobacilli
and Bifidus
in Candida; in
Bifidus and
in Lactobacilli
and Bifidus
No significant
change in Bifidus,
Lactobacilli, or
Impact on
An overview of some of the research investigating the effects of selected antibiotics on the GIT microflora. ↓↓ = strong
suppression (> 4 log 10 CFU/g feces); = mild to moderate suppression (2-4 log 10 CFU/g feces); = increase in number of
organisms during therapy; - = no significant change; = decrease; + = positive result; Bifidus= Bifidobacterium spp.
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In terms of pharmacokinetics, the rate of
intestinal absorption plays a fundamental role.
Also important is whether the drug is excreted in
its active form in bile or saliva. Both of these phar-
macokinetic factors determine the drug’s ultimate
concentration in the intestinal lumen and, hence,
the severity of the microfloral alteration.
In gen-
eral, oral antimicrobials well absorbed in the small
intestine will have minor impact on the colonic
flora, whereas agents that are poorly absorbed can
cause significant changes. Parenteral administra-
tion of antimicrobial agents is not free from these
consequences, as some of these agents can be se-
creted in their active forms in bile, saliva, or from
the intestinal mucosa, and result in considerable
alterations in the colonic flora.
The dosage and length of administration
of an antibiotic will also determine the magnitude
of impact on the intestinal flora. In general, the
greater the dosage and length of administration,
the larger the impact on the microflora.
1a-1d provide an overview of research investigat-
ing the effects of specific antibiotics on GIT mi-
croflora. In general, the trials were conducted on
healthy humans and involved only a single course
of antibiotics. It is possible microfloral alterations
induced by a particular antibiotic might be more
severe in individuals with compromised health or
who have been subjected to multiple courses of
Recent epidemiological research has
shown that individuals who had taken only one
course of antibiotics had significantly lower serum
concentrations of enterolactone up to 16 months
post-antibiotic use compared to individuals who
had remained antibiotic-free during the same time
period (p<0.05). As serum concentrations of
enterolactone are dependent on colonic conversion
of plant lignans to enterolactone by the intestinal
microflora (via beta-glycosidation), this study
suggests infrequent antibiotic use has much longer-
lasting effects on the microflora and its metabolic
activities than was previously believed.
negative association between serum enterolactone
levels and antibiotic use has clinical importance
due to recent studies showing correlations between
high serum enterolactone concentrations and
protection from cardiovascular mortality
breast cancer.
If an antimicrobial agent severely impacts
the microflora, negative repercussions on host
health can result, and include:
• Overgrowth of already-present micro-
organisms, such as fungi or Clostridium difficile.
Overgrowth of these organisms is a frequent cause
of antibiotic-associated diarrhea, and overgrowth
of C. difficile can develop into a severe life-threat-
ening infection.
• Decreased production of SCFAs, which
can result in electrolyte imbalances and diarrhea.
Short-chain fatty acids play a vital role in electro-
lyte and water absorption in the colon.
production of SCFAs post-antibiotic use may be a
causative factor in antibiotic-associated diarrhea.
Short-chain fatty acids also contribute to host
health in other ways, such as improving colonic
and hepatic blood flow,
increasing the solubility
and absorption of calcium,
increasing the absorp-
tive capacity of the small intestine,
and main-
taining colonic mucosal integrity.
• Increased susceptibility to intestinal
pathogens due to the decrease in colonization re-
A decrease in colonization resistance
after antibiotic administration has been observed
in animal models. Such experiments have shown
that disruption of normal microflora decreases the
number of pathogens necessary to cause an infec-
tion and lengthens the time of infection.
• Decreased therapeutic effect of some
medicinal herbs and phytoestrogen-rich foods.
The activity of many medicinal herbs depends on
bacterial enzymatic metabolism in the colon. Of
the many enzymes produced by intestinal flora,
bacterial beta-glycosidases probably play the most
significant role, as many active herbal constitu-
ents are glycosides and are inert until the active
aglycone is released via enzymatic hydrolysis.
Herbs such as willow bark (Salix spp.), senna
(Cassia senna), rhubarb (Rheum palmatum),
devil’s claw (Harpagophytum procumbens), soy
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(Glycine max), and red clover (Trifolium pratense)
would be essentially inactive without this colonic me-
Based on the results of the above-de-
scribed epidemiological study,
it can be inferred
that antibiotic use interferes with microbial beta-
glycosidation in the GIT for a considerable period
post-antibiotic administration, which could signifi-
cantly impact the efficacy of many phytotherapeutic
agents prescribed post-antibiotic use.
Hence, antimicrobial agents should be
used sparingly and selected carefully in order to
minimize the impact on GIT microflora.
The Effect of Stress on GIT
To determine whether psychological stress
results in an altered gas-
trointestinal environment,
Bailey and Coe investigated
changes in indigenous GIT
microflora in primates after
maternal separation. GIT mi-
croflora was evaluated in 20
infant rhesus macaques ages
6-9 months who were sepa-
rated from their mothers for
the first time. All infant mon-
keys were found to have typi-
cal fecal bacterial concentra-
tions at baseline. A brief in-
crease in Lactobacilli shed-
ding on the first day post-
separation (p<0.05) was fol-
lowed by a significant decrease in the concentra-
tion of Lactobacilli in the feces (p<0.001). An in-
verse relationship was also found between the fe-
cal concentration of shed pathogens (Shigella spp.
and Campylobacter spp.) and shed Lactobacilli
(p= 0.07). The study demonstrates that psycho-
logical stress can alter the integrity of indigenous
microflora for several days.
Other authors have also theorized the Lac-
tobacilli population responds to stress-induced
changes in GIT physiology, such as inhibition of
gastric acid release,
alterations in GIT motility,
or increased duodenal bicarbonate production.
These changes may result in an intestinal environ-
ment less conducive to Lactobacilli survival, adher-
ence, and replication. Alterations in GIT milieu may
lead to detachment of Lactobacilli from the intesti-
nal epithelium and subsequent passage through the
GIT, thus resulting in decreased numbers of repli-
cating Lactobacilli. This would explain the increased
shedding of Lactobacilli found on the first day of
stress, followed by a dramatic decrease in numbers
of Lactobacilli over the next six days.
The effects of psychological stress on the
intestinal environment have been studied in Soviet
cosmonauts. In general, it was found that on return
from space flight there was a decrease in fecal
Bifidobacteria and Lactobacillus organisms (Table
2). These changes were attributed primarily to stress,
although a diet low in fiber may also have contrib-
The change in microflora observed by
Lizko led to a subsequent decline in colonization
resistance, which in turn resulted in increased num-
bers of potentially pathogenic organisms. It has
been found that exposure to psychological stress
results in a significant reduction in the production
of mucin and a decreased presence of acidic mu-
copolysaccharides on the mucosal surface.
both mucin and acidic mucopolysaccharides are
important for inhibiting adherence of pathogenic
organisms to the gut mucosa, a decrease in either
contributes significantly to successful coloniza-
tion by pathogenic organisms.
Table 2. Stress-associated Changes to GIT Microflora
During preparation
After short flight
After long flight
L. acidophilus
L. casei
L. plantarum
Changes in the Lactobacillus fecal flora in Soviet Cosmonauts (log/mL).
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Lizko states that exposure to stress results
in decreased production of immunoglobulin A
(IgA). As IgA plays a vital role in the defense
against pathogenic organisms by inhibiting bac-
terial adherence and promoting their elimination
from the GIT, Lizko postulates that any decrease
in IgA secretion would most likely increase intes-
tinal colonization by potentially pathogenic
microorganisms (PPMs).
A 1997 study assessed the effects of
psychosocial stress on mucosal immunity,
specifically the effect of emotional stress on secretory
IgA (sIgA) levels.
The study was conducted on
children ages 8-12 years (mean age 9.4 years). Ninety
children were included in the trial – half of whom
had a history of recurrent colds and flu, while the
other half were healthy controls. The results
demonstrated that stressful life events correlated with
a decreased salivary ratio of sIgA to albumin. The
ratio of sIgA to albumin controls for serum leakage
of sIgA and is thought to give a clearer indication of
mucosal immunity than total sIgA concentration. This
result provides additional evidence of the likelihood
of stress effectively decreasing mucosal immunity
and, thus, diminishing intestinal colonization
Other studies on college students have found
sIgA concentrations decrease during or shortly after
Salivary concentrations of sIgA are
inversely associated with norepinephrine concentra-
tions, suggesting sympathetic nervous system acti-
vation suppresses the production and/or release of
Thus, frequent suppression of mucosal im-
munity by the sympathetic nervous system during
stressful experiences could increase colonization of
the intestinal mucosa by PPMs.
Holdeman et al studied factors that affect
human fecal flora. They noted a 20-30 percent rise
in the proportion of Bacteroides fragilis subsp.
thetaiotaomicron in the feces of individuals in re-
sponse to anger or fearful situations. When these situ-
ations were resolved, the concentration of these or-
ganisms in the feces decreased to normal levels.
This effect may be mediated via epinephrine, which
has been shown to stimulate both intestinal motility
and bile flow. As growth of B. fragilis subsp.
thetaiotaomicron is enhanced by bile, this may partly
explain the increased numbers of organisms in re-
sponse to increased epinephrine release.
In vitro experiments conducted by Ernst and
Lyte have demonstrated that several neurochemicals
have the ability to directly enhance the growth of
PPMs. The influence of the catecholamines norepi-
nephrine, epinephrine, dopamine, and dopa were
assessed on two strains of Enterobacteriaceae –
Yersinia enterocolitica and Escherichia coli, and one
strain of Pseudomonadaceae – Pseudomonas
All three bacterial species are poten-
tial pathogens, with Y. enterocolitica
and E. coli
involved in GIT infections and P. aeruginosa in gas-
trointestinal, respiratory, and urinary tract infections.
The concentrations of catecholamines used in the ex-
periment were equivalent to those found in plasma.
The addition of norepinephrine, epinephrine, dopa-
mine, and dopa to the cultures of E. coli resulted in
increased growth when compared to non-catechola-
mine-supplemented control cultures. However, the
largest increase in growth was observed with the
addition of norepinephrine. Norepinephrine caused
a large increase in growth of Y. enterocolitica, while
both dopa and dopamine produced only small, but
significant, increases in growth. Epinephrine dem-
onstrated no effect. Norepinephrine also markedly
increased the growth of P. aeruginosa, while the other
catecholamines appeared to have no effect on this
In vitro experiments performed by Lyte et
al showed exposure of enterotoxigenic and
enterohemorrhagic strains of E. coli to norepineph-
rine resulted in increased growth and the expression
of virulence factors, such as the K99 pilus adhesin,
which is involved in the attachment and penetration
of the bacterium into the host’s intestinal mucosa.
Growth of the enterohemorrhagic E. coli was also
increased, as was its production of Shiga-like toxin-
I and Shiga-like toxin-II. The capability of norepi-
nephrine to enhance both bacterial virulence-associ-
ated factors and growth was shown to be non-nutri-
tional in nature – in other words, the bacteria did not
use norepinephrine as a food; rather, the effect was
via an unknown mechanism.
Additional experiments by Lyte et al dem-
onstrated that upon exposure to norepinephrine, E.
coli produces a growth hormone known as an
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“autoinducer of growth.”
This autoinducer showed
a high degree of cross-species activity with other
gram-negative bacteria, resulting in increased growth
of other organisms. It was later found to stimulate
10- to 10
-fold increases in the growth of 12 of 15
gram-negative microorganisms tested.
Exposure to stress has been documented
to result in dramatic and sustained increases in
catecholamine levels. This high concentration of
catecholamines, and especially norepinephrine,
may result in increased growth of PPMs in the
The GIT has abundant noradrenergic
innervation and a high amount of norepinephrine
is present throughout.
Studies conducted by
Eisenhofer et al showed 45-50 percent of the total
body production of norepinephrine occurs in the
mesenteric organs.
Lyte suggests spillover of
norepinephrine into the lumen of the intestinal tract
undoubtedly occurs due to the concentration gra-
dient present within the mesenteric organs.
there would be no requirement for an active trans-
port system. This spillover effect has previously
been demonstrated for serotonin following its re-
lease from gut enterochromaffin cells.
As such,
the GIT represents an area in which neuroendo-
crine hormones like norepinephrine coexist with
indigenous microflora.
Thus far, catecholamines
have not been found to induce the growth of gram-
positive bacteria.
The effect of norepinephrine on gut flora
was recently demonstrated in a murine model. The
release of norepinephrine into the systemic circula-
tion, caused by neurotoxin-induced noradrenergic
neuron trauma, resulted in increased growth of gram-
negative bacteria within the GIT. The total gram-
negative population increased by 3 log units within
the cecal wall and 5 log units within the cecal con-
tents inside a 24-hour time period. The predominant
species of gram-negative bacteria identified was E.
To summarize, stress can induce significant
alterations in GIT microflora, including a significant
decrease in beneficial bacteria such as Lactobacilli
and Bifidobacteria and an increase in PPMs such as
E. coli. These changes may be caused by the growth-
enhancing effects of norepinephrine on gram-nega-
tive microorganisms or by stress-induced changes
to GIT motility and secretions.
Diet and Intestinal Microflora
The composition of the diet has been
shown to have a significant impact on the content
and metabolic activities of the human fecal flora.
Some diets promote the growth of beneficial
microorganisms, while others promote micro-
floral activity that can be harmful to the host.
Sulfur compounds, including sulfate and
sulfite, have been shown to increase the growth
of PPMs or increase production of potentially
harmful bacterial products in the GIT. In the colon
is a specialized class of gram-negative anaerobes
known as sulfate-reducing bacteria (SRB). SRB
include species belonging to the genera
Desulfotomaculum, Desulfovibrio, Desulfo-
bulbus, Desulfobacter, and Desulfomonas.
principal genus, however, is Desulfovibrio, which
accounts for 64-81 percent of all human colonic
Sulfate-reducing bacteria utilize a process
termed “dissimilatory sulfate reduction” to reduce
sulfite and sulfate to sulfide.
The consequence of
this process is the production of potentially toxic
hydrogen sulfide, which can contribute to abdomi-
nal gas-distension.
Hydrogen sulfide can also
damage colonic mucosa by inhibiting the oxida-
tion of butyric acid, the primary fuel for
enterocytes. Butyrate oxidation is essential for
absorption of ions, mucus synthesis, and lipid syn-
thesis for colonocyte membranes.
This inhibi-
tion of butyrate oxidation is characteristic of the
defect observed in ulcerative colitis and leads to
intracellular energy deficiency, as well as disrup-
tion of essential activities.
Sulfide has also been
shown to cause a substantial increase in mucosal
permeability, presumably due to the breakdown
of the polymeric gel structure of mucin through
the cleavage of disulfide bonds.
Sulfate-reducing bacteria are not present
in all individuals and there appears to be consid-
erable variation in SRB concentrations depend-
ing on geographical location, a variation hypoth-
esized to be connected to dietary differences. Sul-
fate-reducing bacteria directly compete with
methanogenic bacteria (MB) for vital substrates,
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such as hydrogen and acetate. In fact,
methanogenesis and sulfate reduction appear to be
mutually exclusive in the colon. In the presence of
sufficient amounts of sulfate, SRB have been shown
to outcompete MB for both hydrogen and acetate;
whereas, under conditions of sulfate limitation the
reverse occurs.
The amount of dietary sulfate that
reaches the colon appears to be the primary factor in
determining the growth of SRB. On the other hand,
endogenous sources of sulfate (e.g., sulfated glyco-
proteins, chondroitin sulfate) appear to have little
impact on SRB levels.
Sources of dietary sulfate include preserva-
tives, dried fruits (if treated with sulfur dioxide), de-
hydrated vegetables, shellfish (fresh or frozen),
packaged fruit juices, baked goods,
white bread,
and the majority of alcoholic beverages.
It also ap-
pears probable that ingestion of foods rich in sulfur-
containing amino acids encourages both the growth
of SRB and the production of sulfide in the large
Major amounts of sulfur-containing amino
acids are found in cow’s milk, cheese, eggs, meat,
and cruciferous vegetables. Consumption of large
amounts of these foods may significantly increase
sulfide production in the colon.
Research conducted
in the 1960s found elimination of milk, cheese, and
eggs from the diet of ulcerative colitis sufferers re-
sulted in substantial therapeutic benefit, suggesting
that reducing the intake of sulfur-containing amino
acids decreases colonic production of sulfide.
High Protein Diet
Consumption of a high-protein diet can also
increase the production of potentially harmful bac-
terial metabolites. It has been estimated that in indi-
viduals consuming a typical Western diet (contain-
ing ~ 100 g protein/day) as much as 12 g of dietary
protein per day can escape digestion in the upper
GIT and reach the colon.
This is in addition to
host-derived proteins, such as pancreatic and intesti-
nal enzymes, mucins, glycoproteins, and sloughed
epithelial cells.
Undigested protein is fermented by
the colonic microflora with the resultant end-prod-
ucts of SCFAs, branched-chain fatty acids (e.g.,
isovalerate, isobutyrate, and 2-methylbutyrate), and
potentially harmful metabolites – ammonia, amines,
phenols, sulfide, and indoles.
Ammonia has been shown to alter the
morphology and intermediate metabolism, in-
crease DNA synthesis, and reduce the lifespan of
mucosal cells.
It is also considered to be more
toxic to healthy mucosal cells than transformed
cells and, thus, may potentially select for neoplas-
tic growth.
Ammonia production and accumula-
tion is also involved in the pathogenesis of portal-
systemic encephalopathy.
Indoles, phenols, and
amines have been implicated in schizophrenia
and migraines.
Indoles and phenols are also
thought to act as co-carcinogens
and may play a
role in the etiology of bladder and bowel cancer.
The production of these potentially toxic
compounds has been found to be directly related
to dietary protein intake,
a reduction of which can
decrease production of harmful by-products.
production of these potentially harmful by-prod-
ucts can also be attenuated by the consumption of
diets high in fiber
and/or indigestible starch (both
of which reduce intestinal pH).
Diets High In Animal Protein
In comparison to diets high in overall pro-
tein, diets especially high in animal protein have
specific effects on intestinal microflora. While not
appearing to dramatically alter the bacterial com-
position of the flora compared to control diets,
ingestion of large amounts of animal protein does
increase the activity of certain bacterial enzymes,
such as beta-glucuronidase, azoreductase,
nitroreductase, and 7-alpha-hydroxysteroid
dehydroxylase, in animals
and humans.
can have important ramifications to the host, as
any increase in activity of these enzymes will re-
sult in increased release of potentially toxic me-
tabolites in the bowel. For instance, bacterial
azoreductase can reduce the azo bond found in
many synthetic food-coloring agents, releasing
substituted phenyl and napthyl amines, some of
which are known to be potent carcinogens.
other example is the action of the bacterial beta-
glucuronidases. Many xenobiotics are processed
in the liver by a series of reactions that result in
glucuronic acid conjugation. These glucuronides
are then passed, via the biliary system, to the in-
testines. When these compounds reach the colon
Alternative Medicine Review
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they can be hydrolyzed by beta-glucuronidase pro-
duced by the microflora, resulting in the release
of the original xenobiotic, which then re-enters
enterohepatic circulation and is recirculated sev-
eral times before eventually being eliminated
through the feces. If the original xenobiotic is
mutagenic, carcinogenic, or otherwise toxic, this
process can be detrimental to the host.
The nu-
trient calcium D-glucarate exerts its potentially
beneficial effects by inhibiting beta-glucuronidase.
High Simple Sugar/Refined Carbohydrate
Kruis et al observed that diets high in simple
sugars slow bowel transit time and increase fermen-
tative bacterial activity and fecal concentrations of
total and secondary bile acids in the colon.
A con-
sequence of slower bowel transit time may be an in-
creased exposure to potentially toxic bowel con-
The mechanism by which high-sugar diets
increase bowel transit time is not yet known.
Table 3. The Effects of Various Diets on GIT Microflora
Total anaerob es
Total aerob es
Bacteroides spp.
Bifidobact eria
Western Diet
Seventh D ay
Vegetarian D iet
Western Diet
Japanese Diet
Western Diet
Vegetarian D iet
Effect of Western vs. vegetarian or high carbohydrate diets on the h uman fecal flora (- = no data ; Ψ = a significant difference
between gro ups;
= log10 mean c ount/g wet weight of f eces;
= log10 mean c ount/g dry weight of f eces.)
From: Salminen S, Isolauri E, Onnela T. Gut flora in normal and alter ed states. Chemother 1995;41 (suppl 1):5-15.
Page 192 Alternative Medicine Review
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The increase in colonic fermentative ac-
tivity noted in the Kruis study may not be directly
associated with changes in microflora composi-
tion, but rather be caused by direct exposure of
the colon to simple sugars. Refined sugars are
metabolized quickly in the ascending colon;
whereas, high-fiber foods, containing substantial
amounts of insoluble fiber, are metabolized more
slowly, releasing fermentation end-products (e.g.,
hydrogen gas and SCFAs) more gradually.
It is possible, however, that high sugar
intake does cause alterations in the microflora. It
has been observed that high sugar intakes increase
bile output. Some species of intestinal bacteria
utilize bile acids as food and, hence, any increase
in their production will result in a competitive
advantage for this group of bacteria.
The changes
observed in bacterial fermentation in this study
may or may not be related to changes in the spe-
cies composition of the microflora. Since this was
not adequately assessed in this study, the signifi-
cance of these results requires further investiga-
Other researchers have postulated that
when intake of dietary carbohydrates is
insufficient, increased fermentation of the
protective layer of mucin may occur due to the
limited quantity of carbon sources reaching the
colon. This may compromise mucosal defense and
lead to direct contact between colonic cells and
bacterial products and antigens. This, in turn, may
lead to inflammation and increased mucosal
permeability. Such a situation may encourage the
growth of potentially pathogenic bacteria and
perpetuate the inflammatory response.
theory, however, is yet to be supported by direct
General Dietary Factors
The effect of the overall diet on the
composition and metabolic activities of GIT
microflora has been the subject of research since
the late 1960s. It was initially believed that
changing the content of the diet (in terms of meat,
fat, carbohydrate, and fiber content) would
dramatically alter the bacterial species
composition of the colonic flora. However, when
the diets of various population groups consuming
different diets were analyzed, the changes noted
were not dramatic.
Only minor changes were
noted among the groups, although these changes
were considered to be caused by differences in
Table 3 outlines results of several studies
comparing the fecal flora of individuals consuming
the typical Western diet (high in fat and meat) to
that of individuals eating vegetarian and/or high
complex-carbohydrate diets.
In general, it appears populations consum-
ing the typical Western diet have more fecal
anaerobic bacteria, less Enterococci, and fewer
yeasts than populations consuming a vegetarian
or high complex-carbohydrate diet. Although one
study found a significant difference between a
mixed Western diet and a vegetarian diet, overall
there appear to be relatively few trends.
In spite of these findings, Gorbach argues
that due to the sheer number of bacteria present in
the stool (approximately 10
viable bacteria/g) and
the enormous variety (around 500 anaerobic spe-
cies, not to mention aerobic and facultative spe-
cies), the classical method of quantifying flora is,
at best, a crude approximation. Thus, these meth-
ods may be unable to differentiate changes due to
variations in diet.
In an attempt to create a more sensitive
method to detect changes in human microflora,
Peltonen et al utilized gas-liquid chromatography
(GLC) to analyze profiles of bacterial cellular fatty
acids. This method measures bacterial cellular
fatty acids present in the stool that accumulate to
form a GLC fatty acid profile, with each peak in
the profile representing relative amounts of a par-
ticular fatty acid in the stool. Similar bacterial
compositions should yield similar fatty acid pro-
files, while distinctions can be quantified by the
extent to which profiles differ from each other.
The researchers utilized this technique to analyze
the effects of a vegan, raw food diet on the intes-
tinal microflora. The one-month diet consisted of
a variety of sprouts, fermented vegetables, fruits,
seaweed, nuts, and seeds. Differences in the GLC
profile between the test and control groups were
statistically significant (p<0.05), as were the dif-
ferences in test group GLC profiles before and
Alternative Medicine Review
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during the diet. No significant changes in the fe-
cal flora could be detected in either group using
the traditional isolation, identification, and enu-
meration bacteriological. While GLC may be a
more sensitive method to determine changes in
fecal flora, it cannot identify particular compo-
nents of the flora.
Newer techniques such as fluorescence in
situ hybridization (FISH) or polymerase chain re-
action assays coupled with denaturing gel elec-
are more sensitive to minor alter-
ations in microflora and allow for bacterial iden-
tification that would otherwise be impossible to
The use of these modern techniques in
future diet studies will shed more light on this
contentious area. Interestingly, recent research
utilizing the FISH technique has indicated the
majority of bacteria in the colon are not culturable
and have yet to be described. This finding sug-
gests how little is actually known about the com-
position of GIT microflora.
In summary, research has shown that con-
sumption of foods rich in sulfur compounds, high
in protein, and/or high in meat may produce detri-
mental effects on the host. These changes may be
mediated through alterations in composition of the
microflora or through increased production of
bacterial metabolites. The impact of a high refined-
carbohydrate intake on the microflora has yet to
be clearly elucidated. Similarly, the relationship
between the overall diet and composition of the
microflora awaits further clarification using mod-
ern microbiological techniques.
Alterations in bowel flora and its activities
are now believed to be contributing factors to
many chronic degenerative diseases. Ample
evidence in the literature exists to confirm
dysbiosis as an important clinical entity. It is
therefore imperative to know what factors play a
causative role in this increasingly common
condition. Antibiotics, psychological and physical
stress, and dietary factors contribute to intestinal
dysbiosis. Armed with knowledge of the factors
that contribute to dysbiosis, clinicians are better
equipped to deal with the causes of this condition.
Diets can be altered, the effects of stress attenuated,
and antibiotics used sparingly, in order to minimize
the effects of these factors on intestinal microflora.
If the causes of dysbiosis can be eliminated or at
least attenuated, then treatments aimed at
manipulating the microflora may become more
successful and longer-lasting in effect.
Future research using molecular microbi-
ology techniques will provide definitive answers
to currently unanswered questions regarding the
effects of various factors on the GIT microflora.
Older studies that evaluated the effects of differ-
ent dietary regimes on the GIT flora should be re-
conducted utilizing modern microbiology tech-
niques. These techniques will also provide accu-
rate information regarding how specific drugs or
herbs affect microbial populations in the GIT. This
information will allow far greater precision in both
dietary and herbal prescribing.
1. Bengmark S. Ecological control of the
gastrointestinal tract. The role of probiotic
flora. Gut 1998;42:2-7.
2. Barrie SA, Lee MJ. Intestinal permeability. In:
Pizzorno J, Murray M, eds. Textbook of
Natural Medicine. Seattle, WA: Bastyr College
Publications; 1992:1-5.
3. van Deventer SJ, ten Cate JW, Tytgat GN.
Intestinal endotoxemia. Clinical significance.
Gastroenterology 1988;94:825-831.
4. Cummings JH, Macfarlane GT. Role of
intestinal bacteria in nutrient metabolism.
JPEN J Parenter Enteral Nutr 1997;21:357-
5. Macfarlane S, Macfarlane GT. Proteolysis and
amino acid fermentation. In: Gibson GR,
Macfarlane GT, eds. Human Colonic Bacteria:
Role in Nutrition, Physiology, and Pathology.
Boca Raton, FL: CRC Press; 1995:75-100.
6. Macfarlane GT, Gibson GR. Metabolic
activities of the normal colonic flora. In:
Gibson SAW, ed. Human Health: The Contri-
bution of Microorganisms. London: Springer-
Verlag; 1994:17-53.
7. Donovan P. Bowel toxemia, permeability and
disease: new information to support an old
concept. In: Pizzorno J, Murray M, eds.
Textbook of Natural Medicine. Seattle, WA:
Bastyr College Publications; 1992:1-7.
Page 194 Alternative Medicine Review
Volume 9, Number 2 2004
Intestinal Dysbiosis Review
Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
8. Bengmark S. Prospects for a new and redis-
covered form of therapy: probiotics and phage.
In: Baue AE, Faist E, Fry D, eds. Multiple
Organ FailurE – Pathophysiology, Prevention
and Therapy. New York, NY: Springer-Verlag;
In press.
9. Kirchfeld F, Boyle W. Nature Doctors:
Pioneers in Naturopathic Medicine. East
Palestine: Buckeye Naturopathic Press;
10. Lindlahr H. Philosophy of Natural Therapeu-
tics. Essex: C.W. Daniel Co. Ltd; 1981:89.
11. Metchnikoff E. The Prolongation of Life:
Optimistic Studies. London: William
Heinemann; 1907:161-183.
12. Tannock GW. Probiotic properties of lactic-
acid bacteria: plenty of scope for fundamental
R & D. Trends Biotechnol 1997;15:270-274.
13. Murray M, Pizzorno J. Encyclopedia of
Natural Medicine. Rocklin, CA: Prima
Publishing; 1998:143.
14. Holzapfel WH, Haberer P, Snel J, et al.
Overview of gut flora and probiotics. Int J
Food Microbiol 1998;41:85-101.
15. Balsari A, Ceccarelli A, Dubini F, et al. The
fecal microbial population in the irritable
bowel syndrome. Microbiologica 1982;5:185-
16. Onderdonk AB. Role of the intestinal micro-
flora in ulcerative colitis. In: Hentges DJ, ed.
Human Intestinal Microflora in Health and
Disease. New York, NY: Academic Press;
17. Linskens RK, Huijsdens XW, Savelkoul PH, et
al. The bacterial flora in inflammatory bowel
disease: current insights in pathogenesis and
the influence of antibiotics and probiotics.
Scand J Gastroenterol Suppl 2001;234:29-40.
18. Peltonen R, Nenonen M, Helve T, et al. Faecal
microbial flora and disease activity in rheuma-
toid arthritis during a vegan diet. Br J
Rheumatol 1997;36:64-68.
19. Brandtzaeg P. Review article: Homing of
mucosal immune cells – a possible connection
between intestinal and articular inflammation.
Aliment Pharmacol Ther 1997;11:24-37.
20. Gibson GR. Dietary modulation of the human
gut microflora using prebiotics. Br J Nutr
21. Moore WE, Holdeman LV. Human fecal flora:
the normal flora of 20 Japanese-Hawaiians.
Appl Microbiol 1974;27:961-979.
22. Savage DC. Microbial ecology of the gas-
trointestinal tract. Annu Rev Microbiol
23. Bengmark S. Probiotics and prebiotics in
prevention and treatment of gastrointestinal
diseases. Gastroenterol Int 1998;11:4-7.
24. Macfarlane GT, Macfarlane S. Human colonic
microbiota: ecology, physiology and metabolic
potential of intestinal bacteria. Scand J
Gastroenterol Suppl 1997;222:3-9.
25. Noack J, Kleessen B, Proll J, et al. Dietary
guar gum and pectin stimulate intestinal
microbial polyamine synthesis in rats. J Nutr
26. Gibson GR, Roberfroid MB. Dietary modula-
tion of the human colonic microbiota: intro-
ducing the concept of prebiotics. J Nutr
27. Gismondo MR. Antibiotic impact on intestinal
microflora. Gastroenterol Int 1998;11:29-30.
28. Nord CE. Studies on the ecological impact of
antibiotics. Eur J Clin Microbiol Infect Dis
29. Nord CE, Edlund C. Impact of antimicrobial
agents on human intestinal microflora. J
Chemother 1990;2:218-237.
30. Nord CE, Heimdahl A, Kager L. Antimicrobial
agents and the human oropharyngeal and
intestinal microflora. Ann Ist Super Sanita
31. Kilkkinen A, Pietinen P, Klaukka T, et al. Use
of oral antimicrobials decreases serum
enterolactone concentration. Am J Epidemiol
32. Vanharanta M, Voutilainen S, Rissanen TH, et
al. Risk of cardiovascular disease-related and
all-cause death according to serum concentra-
tions of enterolactone: Kuopio Ischaemic
Heart Disease Risk Factor Study. Arch Intern
Med 2003;163:1099-1104.
33. Boccardo F, Lunardi G, Guglielmini P, et al.
Serum enterolactone levels and the risk of
breast cancer in women with palpable cysts.
Eur J Cancer 2004;40:84-89.
34. Gorbach SL. Perturbation of intestinal micro-
flora. Vet Hum Toxicol 1993;35:15-23.
35. Hurley BW, Nguyen CC. The spectrum of
pseudomembranous enterocolitis and antibi-
otic-associated diarrhea. Arch Intern Med
Alternative Medicine Review
Volume 9, Number 2 2004 Page 195
Review Intestinal Dysbiosis
Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
36. Bengmark S. Econutrition and health mainte-
nance – a new concept to prevent GI inflam-
mation, ulceration and sepsis. Clin Nutr
37. Topping DL, Clifton PM. Short-chain fatty
acids and human colonic function: roles of
resistant starch and nonstarch polysaccharides.
Physiol Rev 2001;81:1031-1064.
38. Mortensen PB, Clausen MR. Antibiotic-
associated diarrhea. In: Binder HJ, Cummings
JH, Soergei K, eds. Short Chain Fatty Acids.
Dordrecht: Kluwer Academic Publishers;
39. Topping DL. Short-chain fatty acids produced
by intestinal bacteria. Asia Pac J Clin Nutr
40. Coudray C, Bellanger J, Castiglia-Delavaud C,
et al. Effect of soluble or partly soluble dietary
fibres supplementation on absorption and
balance of calcium, magnesium, iron and zinc
in healthy young men. Eur J Clin Nutr
41. Clausen MR. Production and oxidation of
short-chain fatty acids in the human colon:
implications for antibiotic-associated diarrhea,
ulcerative colitis, colonic cancer, and hepatic
encephalopathy. Dan Med Bull 1998;45:51-75.
42. Sakata T. Influence of short chain fatty acids
on intestinal growth and functions. In:
Kritchevsky D, Bonfield C, eds. Dietary Fiber
in Health and Disease. New York: Plenum
Press; 1997:191-199.
43. Gorbach SL, Barza M, Giuliano M, Jacobus
NV. Colonization resistance of the human
intestinal microflora: testing the hypothesis in
normal volunteers. Eur J Clin Microbiol Infect
Dis 1988;7:98-102.
44. Hentges DJ. Role of the intestinal microflora
in host defense against infection. In: Hentges
DJ, ed. Human Intestinal Microflora in Health
and Disease. New York: Academic Press;
45. Pengally A. The Constituents of Medicinal
Plants, 2
ed. Crows Nest, Australia: Allen &
Unwin; 2004:43-58.
46. Wohlmuth H. Pharmacognosy and Medicinal
Plant Pharmacology. Lismore, Australia:
Southern Cross University Press; 1998:66-78.
47. Pithie AD, Ellis CJ. Review article: antibiotics
and the gut. Aliment Pharmacol Ther
48. Finegold SM, Mathisen GE, George WL.
Changes in human intestinal flora related to
the administration of antimicrobial agents. In:
Hentges DJ, ed. Human Intestinal Microflora
in Health and Disease. London: Academic
Press; 1983:355-448.
49. Bergan T. Pharmacokinetic differentiation and
consequences for normal microflora. Scand J
Infect Dis Suppl 1986;49:91-99.
50. Samonis G, Gikas A, Toloudis P, et al. Pro-
spective study of the impact of broad-spectrum
antibiotics on the yeast flora of the human gut.
Eur J Clin Microbiol Infect Dis 1994;13:665-
51. Adamsson I, Edlund C, Sjostedt S, Nord CE.
Comparative effects of cefadroxil and
phenoxymethylpenicillin on the normal
oropharyngeal and intestinal microflora.
Infection 1997;25:154-158.
52. Sjovall J, Huitfeldt B, Magni L, Nord CE.
Effect of beta-lactam prodrugs on human
intestinal microflora. Scand J Infect Dis Suppl
53. Cummings JH. Short chain fatty acids. In:
Gibson GR, Macfarlane GT, eds. Human
Colonic Bacteria: Role in Nutrition, Physiol-
ogy and Pathology. Boca Raton, FL: CRC
Press; 1995:101-130.
54. Bailey MT, Coe CL. Maternal separation
disrupts the integrity of the intestinal micro-
flora in infant rhesus monkeys. Dev
Psychobiol 1999;35:146-155.
55. Lenz HJ, Druge G. Neurohormonal pathways
mediating stress-induced inhibition of gastric
acid secretion in rats. Gastroenterology
56. Lenz HJ, Burlage M, Raedler A, Greten H.
Central nervous system effects of corticotro-
pin-releasing factor on gastrointestinal transit
in the rat. Gastroenterology 1988;94:598-602.
57. Lenz HJ. Regulation of duodenal bicarbonate
secretion during stress by corticotropin-
releasing factor and beta-endorphin. Proc Natl
Acad Sci U S A 1989;86:1417-1420.
58. Lizko NN. Stress and intestinal microflora.
Nahrung 1987;31:443-447.
59. Hentges DJ. Gut flora and disease resistance.
In: Fuller R, ed. Probiotics: the Scientific
Basis. London: Chapman and Hall; 1992:87-
Page 196 Alternative Medicine Review
Volume 9, Number 2 2004
Intestinal Dysbiosis Review
Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
60. Drummond PD, Hewson-Bower B. Increased
psychosocial stress and decreased mucosal
immunity in children with recurrent upper
respiratory tract infections. J Psychosom Res
61. Jemmott JB 3rd, McClelland DC. Secretory
IgA as a measure of resistance to infectious
disease: comments on Stone, Cox,
Vladimarsdottir, and Neale. Behav Med
62. Holdeman LV, Good IJ, Moore WE. Human
fecal flora: variation in bacterial composition
within individuals and a possible effect of
emotional stress. Appl Environ Microbiol
63. Moore WE, Cato EP, Holdeman LV. Some
current concepts in intestinal bacteriology. Am
J Clin Nutr 1978;31:S33-S42.
64. Lyte M, Ernst S. Catecholamine induced
growth of gram negative bacteria. Life Sci
65. Serrander R, Magnusson KE, Kihlstrom E,
Sundqvist T. Acute yersinia infections in man
increase intestinal permeability for low-
molecular weight polyethylene glycols (PEG
400). Scand J Infect Dis 1986;18:409-413.
66. Lyte M, Erickson AK, Arulanandam BP, et al.
Norepinephrine-induced expression of the K99
pilus adhesion of enterotoxigenic Escherichia
coli. Biochem Biophys Res Commun
67. University of Wisconsin-Madison, Microbiol-
ogy Textbook. Pseudomonas aeruginosa. http:/
pseudomonas.html. Accessed 5-3-2002.
68. Lyte M, Arulanandam B, Nguyen K, et al.
Norepinephrine induced growth and expres-
sion of virulence associated factors in
enterotoxigenic and enterohaemorrhagic
strains of Escherichia coli. In: Paul P, Francis
D, Benfield D, eds. Mechanisms in the
Pathogenesis of Enteric Diseases. New York,
NY: Plenum Press; 1997:331-339.
69. Lyte M, Frank CD, Green BT. Production of
an autoinducer of growth by norepinephrine
cultured Escherichia coli 0157:H7. FEMS
Microbiol Lett 1996;139:155-159.
70. Freestone PP, Haigh RD, Williams PH, Lyte
M. Stimulation of bacterial growth by heat-
stable, norepinephrine-induced autoinducers.
FEMS Microbiol Lett 1999;172:53-60.
71. Lyte M. The role of microbial endocrinology
in infectious disease. J Endocrinol
72. Eisenhofer G, Aneman A, Hooper D, et al.
Production and metabolism of dopamine and
norepinephrine in mesenteric organs and liver
of swine. Am J Physiol 1995;268:G641-G649.
73. Eisenhofer G, Aneman A, Hooper D, et al.
Mesenteric organ production, hepatic metabo-
lism, and renal elimination of norepinephrine
and its metabolites in humans. J Neurochem
74. Lyte M, Bailey MT. Neuroendocrine-bacterial
interactions in a neurotoxin-induced model of
trauma. J Surg Res 1997;70:195-201.
75. Ahlman H, Bhargava HN, Dahlstrom A, et al.
On the presence of serotonin in the gut lumen
and possible release mechanisms. Acta Physiol
Scand 1981;112:263-269.
76. Levitt MD, Gibson GR, Christl SU. Gas
metabolism in the large intestine. In: Gibson
GR, Macfarlane GT, eds. Human Colonic
Bacteria: Role in Nutrition, Physiology, and
Pathology. Boca Raton, FL: CRC Press;
77. Roediger WE, Moore J, Babidge W. Colonic
sulfide in pathogenesis and treatment of
ulcerative colitis. Dig Dis Sci 1997;42:1571-
78. Gibson GR, Macfarlane GT, Cummings JH.
Occurrence of sulphate-reducing bacteria in
human faeces and the relationship of dissimila-
tory sulphate reduction to methanogenesis in
the large gut. J Appl Bacteriol 1988;65:103-
79. Christl SU, Gibson GR, Cummings JH. Role
of dietary sulphate in the regulation of
methanogenesis in the human large intestine.
Gut 1992;33:1234-1238.
80. Jones GP. Food Processing. In: Wahlqvist ML,
ed. Food and Nutrition: Australasia, Asia, and
the Pacific. St. Leonards, NSW: Allen and
Unwin; 1997:89-96.
81. Marz R. Medical Nutrition from Marz.
Portland, OR: Quiet Lion Press; 1997:297.
82. Wright R, Truelove SC. A controlled therapeu-
tic trial of various diets in ulcerative colitis. Br
Med J 1965;5454:138-141.
83. Birkett A, Muir J, Phillips J, et al. Resistant
starch lowers fecal concentrations of ammonia
and phenols in humans. Am J Clin Nutr
Alternative Medicine Review
Volume 9, Number 2 2004 Page 197
Review Intestinal Dysbiosis
Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
84. Linder MC. Nutrition and metabolism of
proteins. In: Linder MC, ed. Nutritional
Biochemistry and Metabolism, 2
Norwalk, CT: Appleton and Lange; 1991:87-
85. Smith EA, Macfarlane GT. Dissimilatory
amino acid metabolism in human colonic
metabolism. Anaerobe 1997;3:327-337.
86. Murawaki Y, Kobayashi M, Koda M,
Kawasakia H. Effects of lactulose on intestinal
bacterial flora and fecal organic acids in
patients with liver cirrhosis. Hepatol Res
87. Dalgliesh CE, Kelley W, Horning EC. Excre-
tion of a sulphatoxyl derivative of skatole in
pathological studies in man. Biochem J
88. Burns B, Carr-Davis E. Nutritional care in
diseases of the nervous system. In: Mahan K,
Escott-Stump S, eds. Krause’s Food, Nutrition,
and Diet Therapy. Philadelphia, PA: W.B.
Saunders Company; 1996:863-888.
89. Cummings JH, Hill MJ, Bone ES, et al. The
effect of meat protein and dietary fiber on
colonic function and metabolism. II. Bacterial
metabolites in feces and urine. Am J Clin Nutr
90. Gorbach SL. The intestinal microflora and its
colon cancer connection. Infection
91. Goldin BR, Gorbach SL. Alterations of the
intestinal microflora by diet, oral antibiotics,
and Lactobacillus: decreased production of
free amines from aromatic nitro compounds,
azo dyes, and glucoronides. J Natl Cancer
Instit 1984;73:689-695.
92. Goldin B, Gorbach SL. Alterations in fecal
microflora enzymes related to diet, age,
Lactobacillus supplements, and dimethylhy-
drazine. Cancer 1977;40:2421-2426.
93. Gorbach SL, Bengt E. Gustafsson memorial
lecture. Function of the normal human
microflora. Scand J Infect Dis Suppl
94. Wilkins TD, Van Tassel RL. Production of
intestinal mutagens. In: Hentges DJ, ed.
Human Intestinal Microflora in Health and
Disease. Paris: Academic Press; 1983:265-
95. Kruis W, Forstmaier G, Scheurlen C, Stellaard
F. Effect of diets low and high in refined
sugars on gut transit, bile acid metabolism, and
bacterial fermentation. Gut 1991;32:367-371.
96. Lewis SJ, Heaton KW. The metabolic conse-
quences of slow colonic transit. Am J
Gastroenterol 1999;94:2010-2016.
97. Hudson MJ, Marsh PD. Carbohydrate metabo-
lism in the colon. In: Gibson GR, Macfarlane
GT, eds. Human Colonic Bacteria: Role in
Nutrition, Physiology, and Pathology. Boca
Raton, FL: CRC Press; 1995:61-73.
98. Quigley ME, Kelly SM. Structure, function,
and metabolism of host mucus glycoproteins.
In: Gibson GR, Macfarlane GT, eds. Human
Colonic Bacteria: Role in Nutrition, Physiol-
ogy, and Pathology. Boca Raton, FL: CRC
Press; 1995:175-199.
99. McKay DM. Intestinal inflammation and the
gut microflora. Can J Gastroenterol
100. Salminen S, Isolauri E, Onnela T. Gut flora in
normal and disordered states. Chemotherapy
101. Peltonen R, Ling WH, Hanninen O, Eerola E.
An uncooked vegan diet shifts the profile of
human fecal microflora: computerized analysis
of direct stool sample gas-liquid chromatogra-
phy profiles of bacterial cellular fatty acids.
Appl Environ Microbiol 1992;58:3660-3666.
102. Tannock GW, Munro K, Harmsen HJ, et al.
Analysis of the fecal microflora of human
subjects consuming a probiotic product
containing Lactobacillus rhamnosus DR20.
Appl Environ Microbiol 2000;66:2578-2588.
103. Apostolou E, Pelto L, Kirjavainen PV, et al.
Differences in the gut bacterial flora of healthy
and milk-hypersensitive adults, as measured
by fluorescence in situ hybridization. FEMS
Immunol Med Microbiol 2001;30:217-221.
104. Hopkins MJ, Sharp R, Macfarlane GT. Age
and disease related changes in intestinal
bacterial populations assessed by cell culture,
16S rRNA abundance, and community cellular
fatty acid profiles. Gut 2001;48:198-205.
... The gut microbiota also influences the blood-brain barrier and its permeability, activation of peripheral immune system cells, and function of the brain microglia [41]. It has been observed that alterations in the bowel microbiota, called intestinal dysbiosis, occur in patients with chronic diseases, including MetS and depressive disorders [42][43][44][45][46]. When the gut microbiota composition is compromised, properties of the protective barrier are impaired, resulting in an increase in the permeability of the intestinal walls and, as a consequence, in the trespass of antigens into the bloodstream, which cause inflammation [47]. ...
... Due to this connection, the brain regulates gastrointestinal functions, e.g., peristalsis [82,100]. On the other hand, microbial imbalance (dysbiosis), influencing the gut-brain connection, may be contribute to the development of several health problems, including eating disorders, chronic abdominal pain syndrome, gastrointestinal inflammation [42,46], and various neurological diseases (i.e., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) [137][138][139]. A high level of comorbidity between mental conditions such as depression and anxiety and gastrointestinal diseases, e.g., irritable bowel syndrome (IBS) or inflammatory bowel disease, has been observed [46]. ...
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Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.
... Alterations in the composition of gut microbiota can be induced by several exogenous factors, with antibiotic abuse being the most powerful [53,54]. Other factors, including stress, radiation, gastrointestinal infections, and dietary changes, can induce dysbiosis [55]. There are three kinds of dysbiosis: loss of beneficial bacteria, overgrowth of harmful bacteria, and loss of diversity in the gut flora, and in most cases of dysbiosis, all three events occur simultaneously [56]. ...
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The escalating misuse of antibiotics, particularly broad-spectrum antibiotics, has emerged as a pivotal driver of drug resistance. Among these agents, tetracyclines are widely prescribed for bacterial infections, but their indiscriminate use can profoundly alter the gut microbiome, potentially compromising both their effectiveness and safety. This review delves into the intricate and dynamic interplay between tetracyclines and the gut microbiome, shedding light on their reciprocal influence. By exploring the effects of tetracyclines on the gut microbiome and the impact of gut microbiota on tetracycline therapy, we seek to gain deeper insights into this complex relationship, ultimately guiding strategies for preserving antibiotic efficacy and mitigating resistance development.
... Animals support microbial communities, providing a unique ecosystem for microorganisms with complex microbiome-host interactions [1]. The microbiome community can be shaped by host and environmental factors, such as environmental surfaces, exposure to pathogens, and horizontal/vertical bacterial transmission [2][3][4] and may impact host fitness and health [5]. The diversity of these microbial communities influences the host's metabolism, immunity, and nutrient uptake [1,[6][7][8]. ...
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The gut microbiome is important for digestion, host fitness, and defense against pathogens, which provides a tool for host health assessment. Amphibians and their microbiomes are highly susceptible to pollutants including antibiotics. We explored the role of an unmanipulated gut microbiome on tadpole fitness and phenotype by comparing tadpoles of Rana berlandieri in a control group (1) with tadpoles exposed to: (2) Roundup® (glyphosate active ingredient), (3) antibiotic cocktail (enrofloxacin, sulfamethazine, trimethoprim, streptomycin, and penicillin), and (4) a combination of Roundup and antibiotics. Tadpoles in the antibiotic and combination treatments had the smallest dorsal body area and were the least active compared to control and Roundup-exposed tadpoles, which were less active than control tadpoles. The gut microbial community significantly changed across treatments at the alpha, beta, and core bacterial levels. However, we did not find significant differences between the antibiotic- and combination-exposed tadpoles, suggesting that antibiotic alone was enough to suppress growth, change behavior, and alter the gut microbiome composition. Here, we demonstrate that the gut microbial communities of tadpoles are sensitive to environmental pollutants, namely Roundup and antibiotics, which may have consequences for host phenotype and fitness via altered behavior and growth.
... The composition of GM is largely dependent on dietary and environmental factors. However, antibiotic use, stress, and breastfeeding can disturb the composition of the microbiota, altering the physiological functions of the host [6,7]. This alteration in the composition of GM, known as gut dysbiosis, produces different activations of signaling pathways and phenotypic changes in humans, triggering chronic inflammatory processes and cardiometabolic diseases such as obesity, type 2 diabetes (T2D), and cardiovascular diseases [8]. ...
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Background: Persistent gut microbiota (GM) imbalance has been associated with metabolic disease development. This study evaluated the mediating role of waist circumference in the association between GM and insulin resistance (IR) in children. Methods: This cross-sectional study included 533 children aged between 6 and 12. The anthropometry, metabolic markers, and relative abundance (RA) of five intestinal bacterial species were measured. Path coefficients were estimated using path analysis to assess direct, indirect (mediated by waist circumference), and total effects on the association between GM and IR. Results: The results indicated a positive association mediated by waist circumference between the medium and high RA of S. aureus with homeostatic model assessments for insulin resistance (HOMA-IR) and for insulin resistance adiponectin-corrected (HOMA-AD). We found a negative association mediated by waist circumference between the low and medium RA of A. muciniphila and HOMA-IR and HOMA-AD. Finally, when we evaluated the joint effect of S. aureus, L. casei, and A. muciniphila, we found a waist circumference-mediated negative association with HOMA-IR and HOMA-AD. Conclusions: Waist circumference is a crucial mediator in the association between S. aureus and A. muciniphila RA and changes in HOMA-IR and HOMA-AD scores in children.
... The microbiota is responsible for stimulating the immune system; synthesizing vitamins B, K and short-chain fatty acids; inhibiting pathogens; stimulating digestion and nutrient absorption; and inducing increased GIT motility, which is essential for intestinal homeostasis of the host [62]. A normal microbiota contributes to defence mechanisms by stimulating the synthesis of mucins by goblet cells and defensins by Paneth cells, IgA secretion by plasma cells and the maturation of T cells. ...
Amoebiasis is a disease caused by the protozoan parasite Entamoeba histolytica that has a worldwide geographic distribution, with a higher prevalence in developing countries where social and sanitary conditions are considerably precarious. Amoebiasis can be accompanied by severe clinical manifestations such as amoebic colitis and amoebic liver abscess, aggravating the host's condition, with death as one of the consequences. Several health actions and pharmacological strategies have been made to prevent the infection and possible complications of this disease, and have achieved success in containing the disease in most patients. However, some medications such as metroni-dazole can also cause serious complications to the individual because of their potential hepatotoxic effect in addition to producing other side effects. Research directed towards an alternative and effective treatment for amebiasis has been conducted. The use of probiotics has been highlighted as a promising treatment against Entamoeba spp. In this review, we will address the prospects of using probiotics as a treatment for amoebiasis patients. In addition, we will provide information on the biology of Entameba spp.; the clinical manifestations of amoebiasis and a perspective of the use of Weissella para-mesenteroides as a possible treatment.
... Состав микробного сообщества меняется на протяжении всей жизни человека и подвержен как экзогенным, так и эндогенным модификациям. Исследователи цитируют Гиппократа (400 г. до н.э): «Смерть сидит в кишечнике» или «Плохое пищеварение -корень всех зол» [2], показывая, что важность кишечника для здоровья человека давно признана. Возобновившийся в последнее время интерес к структуре и функциям МК высветил ее центральное положение в области здоровья и болезней [3]. ...
This review consolidates the data of recent Russian and foreign research works, considering how gut microbiota composition and gut metabolites can affect metabolic disorders. From the standpoint of modern concepts, the authors discuss the functions of the immune system responsible for maintaining relationships with symbiotic microorganisms, analyze the accumulated information on the participation of metabolites of gut microflora in the development of pathological conditions. According to the results of the last two decades achieved, challenges ahead include translation of findings and mechanisms into clinical practice and development of therapeutic options and regimens that target metabolic risks by modulation of gut microbes and metabolites.
... Dysbiosis patterns commonly observed in IBD patients are characterized by a reduction in the diversity of commensal bacteria, particularly Firmicutes, and a relative increase in species belonging to Enterobacteriaceae [5,[38][39][40]. Multiple factors can disrupt the beneficial members of the gut microbiome, including antibiotic use, psychological and physical stress, radiation, altered gut peristalsis, and dietary changes [41]. Genetic deficiencies, such as mutations in the nucleotide-binding oligomerization domaincontaining protein 2 (NOD2), have also been observed to result in gut dysbiosis in patients [42][43][44][45][46][47][48]. ...
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Background Formyl peptide receptor 2 (Fpr2) plays a crucial role in colon homeostasis and microbiota balance. Commensal E. coli is known to promote the regeneration of damaged colon epithelial cells. The aim of the study was to investigate the connection between E. coli and Fpr2 in the recovery of colon epithelial cells. Results The deficiency of Fpr2 was associated with impaired integrity of the colon mucosa and an imbalance of microbiota, characterized by the enrichment of Proteobacteria in the colon. Two serotypes of E. coli , O22:H8 and O91:H21, were identified in the mouse colon through complete genome sequencing. E. coli O22:H8 was found to be prevalent in the gut of mice and exhibited lower virulence compared to O91:H21. Germ-free (GF) mice that were pre-orally inoculated with E. coli O22:H8 showed reduced susceptibility to chemically induced colitis, increased proliferation of epithelial cells, and improved mouse survival. Following infection with E. coli O22:H8, the expression of Fpr2 in colon epithelial cells was upregulated, and the products derived from E. coli O22:H8 induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency increased susceptibility to chemically induced colitis, delayed the repair of damaged colon epithelial cells, and heightened inflammatory responses. Additionally, the population of E. coli was observed to increase in the colons of Fpr2 −/− mice with colitis. Conclusion Commensal E. coli O22:H8 stimulated the upregulation of Fpr2 expression in colon epithelial cells, and the products from E. coli induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency led to an increased E. coli population in the colon and delayed recovery of damaged colon epithelial cells in mice with colitis. Therefore, Fpr2 is essential for the effects of commensal E. coli on colon epithelial cell recovery.
... Probiotics help in maintaining homeostasis in a dysbiotic gut (McFarland 2014). Gut dysbiosis refers to a change in the composition of resident microflora where the pathogenic microbes outgrow the beneficial bacteria (Hawrelak and Myers 2004). Enteric pathogen-induced enteritis leads to loss of gut epithelial barrier, and as a result, certain enteric pathogens spread to distant organs and induce more severe diseases such as septicemia. ...
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Characterization of new potential probiotics is desirable in the field of research on probiotics for their extensive use in health and disease. Tribes could be an unusual source of probiotics due to their unique food habits and least dependence on medications and consumption of antibiotics. The aim of the present study is to isolate lactic acid bacteria from tribal fecal samples of Odisha, India, and characterize their genetic and probiotic attributes. In this context one of the catalase-negative and Gram-positive isolates, identified using 16S rRNA sequencing as Ligilactobacillus salivarius, was characterized in vitro for its acid and bile tolerance, cell adhesion and antimicrobial properties. The whole genome sequence was obtained and analyzed for strain level identification, presence of genomic determinants for probiotic-specific features, and safety. Genes responsible for its antimicrobial and immunomodulatory functions were detected. The secreted metabolites were analyzed using high resolution mass spectroscopy; the results indicated that the antimicrobial potential could be due to the presence of pyroglutamic acid, propionic acid, lactic acid, 2-hydroxyisocaproic acid, homoserine, and glutathione, and the immuno-modulating activity, contributed by the presence of short chain fatty acids such as acetate, propionate, and butyrate. So, to conclude we have successfully characterized a Ligilactobacillus salivarius species with potential antimicrobial and immunomodulatory ability. The health-promoting effects of this probiotic strain and/or its derivatives will be investigated in future.
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Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn's disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.. In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA). We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels. In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels. Aims its connections with We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression. In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels. This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.
The dysbiosis of microbiota has been reported to be associated with numerous human pathophysiological processes, including Inflammatory Bowel Disease (IBD). With advancements in high-throughput sequencing, various methods have been developed to study the alteration of microbiota in the development and progression of diseases. However, a suitable approach to assess the global stability of the microbiota in disease states through time-series microbiome data is yet to be established. In this study, we introduce a novel Energy Landscape construction method, which incorporates the Latent Dirichlet Allocation (LDA) model and the pairwise Maximum Entropy (MaxEnt) model, and demonstrate its utility by applying it to an IBD time-series dataset. Through this method, we obtained the "energy" profile for the potential patterns of microbiota to occur under disease, indicating their stability and prevalence. The results suggest the potential contribution of several microbial genera, including Bacteroides, Alistipes, and Faecalibacterium, as well as their interactions, to the development of IBD. Our proposed method provides a novel and insightful tool for understanding the alteration and stability of the microbiota under disease states and offers a more holistic view of its complex dynamics at play in microbiota-mediated disease.
In both health and disease, the colonic microbiota plays an important role in several areas of human physiology. This complex assemblage of microorganisms endows great metabolic potential on the large intestine, primarily through its degradative abilities. Many hundreds of different types of bacteria, varying widely in physiology and biochemistry, exist in a multitude of different microhabitats in the lumen of the large gut, the mucin layer and on mucosal surfaces. Both microbiota and host obtain clear benefits from association. For example, growth substrates from diet and body tissues, together with a relatively stable environment for bacteria to proliferate are provided by the host, which in turn has evolved to use butyrate, a bacterial fermentation product, as its principal source of energy for epithelial cells in the distal bowel. The main sources of carbon and energy for intestinal bacteria are complex carbohydrates (starches, non- starch polysaccharides). Carbohydrate metabolism is of great importance in the large intestine, since genetically, and in terms of absolute numbers, the vast majority of culturable microorganisms are saccharolytic. The amounts and types of fermentation products formed by colonic bacteria depend on the relative amounts of each substrate available, their chemical structures and compositions, as well as the fermentation strategies (biochemical characteristics and catabolite regulatory mechanisms) of bacteria participating in depolymerization and fermentation of the substrates. Protein breakdown and dissimilatory amino acid metabolism result in the formation of a number of putatively toxic metabolites, including phenols, indoles and amines. Production of these substances is inhibited or repressed in many intestinal microorganisms by a fermentable source of carbohydrate. Owing to the anatomy and physiology of the colon, putrefactive processes become quantitatively more important in the distal bowel, where carbohydrate is more limiting.
Conference Paper
Although largely unproven in humans, better resistance to pathogens, reduction in blood lipids, antitumor properties, hormonal regulation and immune stimulation may all be possible through gut microflora manipulation. One approach advocates the oral intake of live microorganisms (probiotics). Although the probiotic approach has been extensively used and advocated, survivability/viability after ingestion is difficult to guarantee and almost impossible to prove. The prebiotic concept dictates that non viable dietary components fortify certain components of the intestinal flora (e.g., bifidobacteria, lactobacilli). This concept has the advantage that survival of the ingested ingredient-through the upper gastrointestinal tract is not a prerequisite because it is indigenous bacterial genera that are targeted. The feeding of oligofructose and inulin to human volunteers alters the gut flora composition in favor of bifidobacteria, a purportedly beneficial genus. Future human studies that exploit the use of modern molecular-based detection methods for bacteria will determine the efficacy of prebiotics. It may be possible to address prophylactically certain gastrointestinal complaints through the selective targeting of gut bacteria.
The conventional view of the human large bowel as an appendage of the digestive tract, whose principal purpose was the conservation of salt and water and the disposal of waste materials, is increasingly being replaced with that of a highly specialised digestive organ, which through the activities of its constituent microbiota rivals the liver in its metabolic capacity and in the diversity of its biochemical transformations.