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Abstract

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
E-mail: jhawre10@scu.edu.au
Stephen P Myers, PhD, BMed, ND – Professor and Head of
the Australian Centre for Complementary Medicine
Education and Research.
Abstract
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.
(Altern Med Rev 2004;9(2):180-197)
Introduction
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
2
.
Over a normal lifetime, approximately 60 tons of
food will pass through the GIT.
1
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.
2
As mentioned above, the mucosa is ex-
posed to bacterial products – endotoxins,
3
hydro-
gen sulphide,
4
phenols, ammonia, and indoles
5
that can have detrimental effects on both mucosal
and host health.
5
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
6
and sulfate (derived primarily from food addi-
tives)
4
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.
7
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....”
8
More
modern proponents of the bowel toxemia theory
have included naturopath Louis Kuhne in the late
nineteenth century,
9
as well as naturopath Henry
Lindlahr
10
and Nobel prize laureate Elie
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Alternative Medicine Review
Volume 9, Number 2 2004 Page 181
Review Intestinal Dysbiosis
Metchnikoff in the early twentieth century.
11
Louis
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.
9
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
microflora.
11,12
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.
13
Dysbiosis has been defined by
others as “...qualitative and quantitative changes
in the intestinal flora, their metabolic activity and
their local distribution.”
14
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.
13
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)
15
and
inflammatory bowel disease (IBD),
16,17
as well as
more systemic conditions such as rheumatoid ar-
thritis (RA)
18
and ankylosing spondylitis.
19
Thus,
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
Microflora
The microflora of the gastrointestinal tract
represents an ecosystem of the highest complex-
ity.
14
The microflora is believed to be composed
of over 50 genera of bacteria
20
accounting for over
500 different species.
21
The adult human GIT is
estimated to contain 10
14
viable microorganisms,
which is 10 times the number of eukaryotic cells
found within the human body.
22
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).
23
Indeed, this microbe organ
is now recognized as rivaling the liver in the num-
ber of biochemical transformations and reactions
in which it participates.
24
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.
14,25,26
Factors that Can Alter the GIT
Microflora
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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Intestinal Dysbiosis Review
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Table 1a. The Effects of Some Selected Antibiotics on GIT Microflora
Agent
Ampicillin
Ampicillin/
Sulbactam
Amoxicillin
Amoxicillin/
clavulanic acid
Azlocillin
Aztreonam
Bacampillicin
Cefaclor
Cefaloridine
Cefazolin
Cefbuperazone
Cefixime
Cefmenoxime
Entero-
bacteria
↓↓
↓↓
↓↓
↓↓
Entero-
cocci
↓↓
Anaerobic
bacteria
↓↓
↓↓
↓↓
Overgrowth
of resistant
strains
+
+
+
+
+
+
+
+
+
+
Days to
normalization
of flora (post-
administration)
not stated
14
not stated
not stated
29
not stated
14
29
not stated
7
not stated
29
not stated
29
28
14
not stated
Other
in Lactobacilli
and Bifidus; in
Candida;
production of
SCFAs
29,36,48
in Lactobacilli
and Bifidus
29,48
in Candida
29
in Lactobacilli
29
No significant
change in
Lactobacilli,
Bifidus or
yeasts
29,48
in Bifidus;
in C. difficile
29
in Lactobacilli
and Bifidus
29
in Bifidus; in
C. difficile
29
in Lactobacilli
and Bifidus; in
Candida and
Clostridia
29
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
Agent
Cefoperazone
Cefotaxime
Cefotetan
Cefotiam
Cefoxitin
Ceftazadime
Ceftizoxime
Ceftriaxone
Cephradine
Cephrocile
Entero-
bacteria
↓↓
↓↓
Entero-
cocci
↓↓
↓↓
Anaerobic
bacteria
Overgrowth
of resistant
strains
+
+
+
+
+
+
+
Days to
normalization
of flora (post-
administration)
not stated
not stated
29
not stated
not stated
not stated
not stated
not stated
28
not stated
4
Other
in Lactobacilli
and Bifidus; in
C. difficile and
Candida; 70% of
drug excreted in
bile
29,48,49
in Lactobacilli;
in C. difficile
29
in Candida and
Pseudomonas;
in Lactobacilli
29
in Lactobacilli
and Bifidus; in
C. difficile and
Candida
29,48
in Lactobacilli
29
No effect on
Lactobacilli; in
Citrobacter spp.
and Proteus
spp.
29
in Bifidus; in
Candida; 30% of
drug excreted in
bile
29,49
No in yeast
29
in C. difficile
29
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
Agent
Ciprofloxacin
Clindamycin
Doxycycline
Enoxacin
Erythromycin
Imipenem/
cilastatin
Lomefloxacin
Metronidazole
Moxalactam
Norfloxacin
Ofloxacin
Entero-
bacteria
↓↓
↓↓
↓↓
↓↓
↓↓
↓↓
↓↓
Entero-
cocci
↓↓
↓↓
Anaerobic
bacteria
↓↓
↓↓
↓↓
Overgrowth
of resistant
strains
+
+
+
+
Days to
normalization
of flora (post-
administration)
7
14
not stated
14
not stated
14
21
29
not stated
14
14
29
Other
in yeast
colonization; no
effect on Bifidus
or Clostridia
29,50
10% of drug
excreted in bile;
production of
SCFAs; in
Bifidus and
Lactobacilli
29,36,48,49
No effect on
SCFA
production
29,36
in Candida
29
No significant
change in
Lactobacilli or
Bifidus; in yeast
colonization;
production of
SCFAs
29,36,48
in Lactobacilli
and Bifidus
29
No significant
change in
Lactobacilli,
yeasts, Bifidus, or
SCFA
production
29,36,48
in Lactobacilli
and Bifidus; in
Candida and
C. difficile
29,48
in Lactobacilli
and Bifidus; in
Candida
29
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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The Impact of Antibiotics on GIT
Microflora
Antibiotic use is the most common and
significant cause of major alterations in normal
GIT microbiota.
27
The potential for an
antimicrobial agent to influence gut microflora is
related to its spectrum of activity,
27
pharmacokinetics, dosage,
28
and length of
administration.
29
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.
27
Table 1d. The Effects of Some Selected Antibiotics on GIT Microflora
Agent
Pefloxacin
Phenoxymethyl-
penicillin
Piperacillin
Pivampicillin
Pivmecillinam
Talampicillin
Temocillin
Tetracycline
Ticarcillin/
Clavulanic acid
Tinidazole
Entero-
bacteria
↓↓
↓↓
↓↓
Entero-
cocci
Anaerobic
bacteria
Overgrowth
of resistant
strains
+
+
+
+
Days to
normalization
of flora (post-
administration)
not stated
14
not stated
29
not stated
not stated
not stated
29
not stated
29
not stated
not stated
not stated
Other
No effect on
Candida
29
No significant
change in Bifidus;
larger doses
Lactobacilli
29,48,51
in Candida;
no change in
Bifidus or
Lactobacilli
29,48,52
in Lactobacilli
and Bifidus
29,48
in Candida; in
Bifidus and
Lactobacilli
29,48
in Lactobacilli
and Bifidus
29
No significant
change in Bifidus,
Lactobacilli, or
SCFAs
29,48,53
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.
27
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.
30
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.
29
Tables
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
antibiotics.
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.
31
This
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
32
and
breast cancer.
33
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.
34
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.
35
• Decreased production of SCFAs, which
can result in electrolyte imbalances and diarrhea.
36
Short-chain fatty acids play a vital role in electro-
lyte and water absorption in the colon.
37
Reduced
production of SCFAs post-antibiotic use may be a
causative factor in antibiotic-associated diarrhea.
38
Short-chain fatty acids also contribute to host
health in other ways, such as improving colonic
and hepatic blood flow,
39
increasing the solubility
and absorption of calcium,
40
increasing the absorp-
tive capacity of the small intestine,
41
and main-
taining colonic mucosal integrity.
42
• Increased susceptibility to intestinal
pathogens due to the decrease in colonization re-
sistance.
43
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.
44
• Decreased therapeutic effect of some
medicinal herbs and phytoestrogen-rich foods.
31
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.
45
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-
tabolism.
45,46
Based on the results of the above-de-
scribed epidemiological study,
31
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.
47
The Effect of Stress on GIT
Microflora
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.
54
Other authors have also theorized the Lac-
tobacilli population responds to stress-induced
changes in GIT physiology, such as inhibition of
gastric acid release,
55
alterations in GIT motility,
56
or increased duodenal bicarbonate production.
57
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.
54
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-
uted.
58
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.
58
Since
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.
59
Table 2. Stress-associated Changes to GIT Microflora
During preparation
After short flight
After long flight
L. acidophilus
4.0
1.7
2.9
L. casei
3.5
0
0
L. plantarum
2.6
0.5
0
Changes in the Lactobacillus fecal flora in Soviet Cosmonauts (log/mL).
58
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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).
58
A 1997 study assessed the effects of
psychosocial stress on mucosal immunity,
specifically the effect of emotional stress on secretory
IgA (sIgA) levels.
60
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
resistance.
Other studies on college students have found
sIgA concentrations decrease during or shortly after
examinations.
61
Salivary concentrations of sIgA are
inversely associated with norepinephrine concentra-
tions, suggesting sympathetic nervous system acti-
vation suppresses the production and/or release of
sIgA.
60
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.
62
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.
63
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
aeruginosa.
64
All three bacterial species are poten-
tial pathogens, with Y. enterocolitica
65
and E. coli
66
involved in GIT infections and P. aeruginosa in gas-
trointestinal, respiratory, and urinary tract infections.
67
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
organism.
64
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.
68
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.”
69
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
4
-fold increases in the growth of 12 of 15
gram-negative microorganisms tested.
70
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
intestines.
61
The GIT has abundant noradrenergic
innervation and a high amount of norepinephrine
is present throughout.
71
Studies conducted by
Eisenhofer et al showed 45-50 percent of the total
body production of norepinephrine occurs in the
mesenteric organs.
72,73
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.
74
Thus,
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.
75
As such,
the GIT represents an area in which neuroendo-
crine hormones like norepinephrine coexist with
indigenous microflora.
74
Thus far, catecholamines
have not been found to induce the growth of gram-
positive bacteria.
70
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.
coli.
74
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.
20
Some diets promote the growth of beneficial
microorganisms, while others promote micro-
floral activity that can be harmful to the host.
Sulfates
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.
76
The
principal genus, however, is Desulfovibrio, which
accounts for 64-81 percent of all human colonic
SRB.
Sulfate-reducing bacteria utilize a process
termed “dissimilatory sulfate reduction” to reduce
sulfite and sulfate to sulfide.
4
The consequence of
this process is the production of potentially toxic
hydrogen sulfide, which can contribute to abdomi-
nal gas-distension.
76
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.
77
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.
4
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.
4
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.
78
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.
79
Sources of dietary sulfate include preserva-
tives, dried fruits (if treated with sulfur dioxide), de-
hydrated vegetables, shellfish (fresh or frozen),
80
packaged fruit juices, baked goods,
81
white bread,
and the majority of alcoholic beverages.
6
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
bowel.
4
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.
77
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.
82
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.
83,84
This is in addition to
host-derived proteins, such as pancreatic and intesti-
nal enzymes, mucins, glycoproteins, and sloughed
epithelial cells.
5
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.
5,77,85
Ammonia has been shown to alter the
morphology and intermediate metabolism, in-
crease DNA synthesis, and reduce the lifespan of
mucosal cells.
6
It is also considered to be more
toxic to healthy mucosal cells than transformed
cells and, thus, may potentially select for neoplas-
tic growth.
5
Ammonia production and accumula-
tion is also involved in the pathogenesis of portal-
systemic encephalopathy.
86
Indoles, phenols, and
amines have been implicated in schizophrenia
87
and migraines.
88
Indoles and phenols are also
thought to act as co-carcinogens
5
and may play a
role in the etiology of bladder and bowel cancer.
83
The production of these potentially toxic
compounds has been found to be directly related
to dietary protein intake,
6
a reduction of which can
decrease production of harmful by-products.
89
The
production of these potentially harmful by-prod-
ucts can also be attenuated by the consumption of
diets high in fiber
89
and/or indigestible starch (both
of which reduce intestinal pH).
83
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,
90
such as beta-glucuronidase, azoreductase,
nitroreductase, and 7-alpha-hydroxysteroid
dehydroxylase, in animals
91,92
and humans.
93
This
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.
90
An-
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
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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.
94
The nu-
trient calcium D-glucarate exerts its potentially
beneficial effects by inhibiting beta-glucuronidase.
High Simple Sugar/Refined Carbohydrate
Diet
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.
95
A con-
sequence of slower bowel transit time may be an in-
creased exposure to potentially toxic bowel con-
tents.
96
The mechanism by which high-sugar diets
increase bowel transit time is not yet known.
95
Table 3. The Effects of Various Diets on GIT Microflora
Microorganisms
Total anaerob es
Total aerob es
Bacteroides spp.
Enterococci
Bifidobact eria
Lactobacilli
Clostridia
Yeasts
American/
Mixed
Western Diet
10.2
a
7.5
a
9.8
a
5.5
a
10.0
a
7.3
a
4.4
a
American/
Seventh D ay
Adventist
Vegetarian D iet
11.7
b
6.5
b
8.1
b
10.0
b
8.6
b
English/
Mixed
Western Diet
10.1
a
8.0
a
9.8
a
9.7
a
Ψ
5.8
a
5.7
a
Ψ
9.8
a
9.9
a
Ψ
6.5
a
6.0
a
Ψ
5.0
a
4.4
a
1.3
a
Ψ
Japanese/
Japanese Diet
9.9
a
11.4
b
9.4
a
9.8
b
9.4
a
10.1
b
8.1
a
8.4
b
9.7
a
8.2
b
7.4
a
5.7
b
5.1
a
9.7
b
Japanese/
Mixed
Western Diet
11.5
b
9.6
b
11.1
b
8.4
b
9.5
b
4.0
b
9.5
b
Ugandan/
Vegetarian D iet
9.3
a
8.2
a
8.2
a
8.2
a
Ψ
7.0
a
7.0
a
Ψ
9.3
a
9.3
a
Ψ
7.2
a
7.2
a
Ψ
4.6
a
4.0
a
3.1
a
Ψ
Indian/
Vegetarian
Diet
9.7
a
8.2
a
9.2
a
7.3
a
9.6
a
7.6
a
5.0
a
Effect of Western vs. vegetarian or high carbohydrate diets on the h uman fecal flora (- = no data ; Ψ = a significant difference
between gro ups;
a
= log10 mean c ount/g wet weight of f eces;
b
= 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.
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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.
97
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.
63
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-
tion.
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.
98,99
This
theory, however, is yet to be supported by direct
evidence.
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.
93
Only minor changes were
noted among the groups, although these changes
were considered to be caused by differences in
diet.
100
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
11
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.
90
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
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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.
101
Newer techniques such as fluorescence in
situ hybridization (FISH) or polymerase chain re-
action assays coupled with denaturing gel elec-
trophoresis
102
are more sensitive to minor alter-
ations in microflora and allow for bacterial iden-
tification that would otherwise be impossible to
culture.
103
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.
104
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.
Conclusion
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.
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... Dysbiosis, which is defined as the quantitative and qualitative imbalance in the microbiota composition and in the subsequent relevant changes in cytokine production ( Table 2) [36][37][38][39][40], has been linked to several diseases. ...
... It is a normal commensal, and S. thermophilus levels are increased in subjects with metabolic syndrome and IBS (d) sensitization: resulting from an immune response to components of the intestinal microbiota and exemplified by a deficit in the immune barrier composed of secretory IgA; (e) fungal dysbiosis: diet rich in simple sugars, leavened foods, and refined carbohydrates and low in fibers, which favor excessive and unbalanced growth of Candida spp. and yeast microorganisms in the intestines [37,38,[41][42][43]. ...
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Gut microbiota refers to those microorganisms in the human digestive tract that display activities fundamental in human life. With at least 4 million different bacterial types, the gut microbiota is composed of bacteria that are present at levels sixfold greater than the total number of cells in the entire human body. Among its multiple functions, the microbiota helps promote the bioavailability of some nutrients and the metabolization of food, and protects the intestinal mucosa from the aggression of pathogenic microorganisms. Moreover, by stimulating the production of intestinal mediators able to reach the central nervous system (gut/brain axis), the gut microbiota participates in the modulation of human moods and behaviors. Several endogenous and exogenous factors can cause dysbiosis with important consequences on the composition and functions of the microbiota. Recent research underlines the importance of appropriate physical activity (such as sports), nutrition, and a healthy lifestyle to ensure the presence of a functional physiological microbiota working to maintain the health of the whole human organism. Indeed, in addition to bowel disturbances, variations in the qualitative and quantitative microbial composition of the gastrointestinal tract might have systemic negative effects. Here, we review recent studies on the effects of physical activity on gut microbiota with the aim of identifying potential mechanisms by which exercise could affect gut microbiota composition and function. Whether physical exercise of variable work intensity might reflect changes in intestinal health is analyzed.
... Intestinal dysbiosis is a bacteriological imbalance constituting an imbalance in the proportion and type of the gastrointestinal microbiota. The lack of or full absence of essential microorganisms is the main cause of this process [101]. The degree of pathogenicity of microorganisms, the patient's age, somatic disorders, the influence of adverse ecological and environmental elements, the use of antibacterial medications, or an improper diet all contribute to intestinal development dysbiosis [102]. ...
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The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardio-vascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry & Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and [email protected] were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: (“microbio*” and “demineralization*”) AND (“oral microbiota” and “demineralization”). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the.
... A complex symbiosis exists between the human body and its microbiota, modeled by the known plasticity of the gut microbiota; in fact, microbiota composition remains relatively unchanged during acute perturbations, allowing it to rapidly rearrange itself (55). Although chronic exposition to harmful stress factors can profoundly alter the relationship among microorganisms, leading to an imbalanced equilibrium of microbial species known as dysbiosis, which has been often associated with the development of diverse diseases (56). It is known that the dysbiosis can influence the gastrointestinal tract (diarrhea, irritable bowel syndrome; 57), the immune system (allergy, multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and rheumatoid arthritis; 58), the central nervous system (Alzheimer and Parkinson diseases and autism; 59), and host energy metabolism (obesity, T2D, and atherosclerosis; 60). ...
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Obesity is the epidemic of our era and its incidence is supposed to increase by more than 30% by 2030. It is commonly defined as a chronic and metabolic disease with an excessive accumulation of body fat in relation to fat-free mass, both in terms of quantity and distribution at specific points on the body. The effects of obesity have an important impact on different clinical areas, particularly endocrinology, cardiology, and nephrology. Indeed, increased rates of obesity have been associated with increased risk of cardiovascular disease (CVD), cancer, type 2 diabetes (T2D), dyslipidemia, hypertension, renal diseases, and neurocognitive impairment. Obesity-related chronic kidney disease (CKD) has been ascribed to intrarenal fat accumulation along the proximal tubule, glomeruli, renal sinus, and around the kidney capsule, and to hemodynamic changes with hyperfiltration, albuminuria, and impaired glomerular filtration rate. In addition, hypertension, dyslipidemia, and diabetes, which arise as a consequence of overweight, contribute to amplifying renal dysfunction in both the native and transplanted kidney. Overall, several mechanisms are closely related to the onset and progression of CKD in the general population, including changes in renal hemodynamics, neurohumoral pathways, renal adiposity, local and systemic inflammation, dysbiosis of microbiota, insulin resistance, and fibrotic process. Unfortunately, there are no clinical practice guidelines for the management of patients with obesity-related CKD. Therefore, dietary management is based on the clinical practice guidelines for the nutritional care of adults with CKD, developed and published by the National Kidney Foundation, Kidney Disease Outcome Quality Initiative and common recommendations for the healthy population. Optimal nutritional management of these patients should follow the guidelines of the Mediterranean diet, which is known to be associated with a lower incidence of CVD and beneficial effects on chronic diseases such as diabetes, obesity, and cognitive health. Mediterranean-style diets are often unsuccessful in promoting efficient weight loss, especially in patients with altered glucose metabolism. For this purpose, this review also discusses the use of non-classical weight loss approaches in CKD, including intermittent fasting and ketogenic diet to contrast the onset and progression of obesity-related CKD.
... In normalcy, homeostasis is maintained through a cordial interaction between the host and the infinite number of resident microbes that populate the entire stretch of our body. Amassed scientific reports have emphasized the critical role of the microbiota and microbiome in human health and disease and have underscored that microbial dysbiosis contributes to the pathogenesis of lifestyle disorders, auto-immune, neuropsychiatric, and even neoplastic diseases [9,10]. Hence, the microbiota is regarded as the master key and clinical experts have embarked on the journey to explore and target the human microbiome to treat various eye diseases. ...
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... These chronic inflammatory diseases often exist as comorbidities with common physiological manifestations, compounding patient burden and suggesting common origins [38][39][40]. While a number of genetic and environmental factors contribute to the manifestation of chronic disease, an emerging assumption postulates that dysbiosis, an imbalance in the composition and metabolic capacity of our microbiota, increases the risk of developing chronic disease [41][42][43][44]. Plant foods can enhance inflammation, obesity and microbiota in a variety of ways. ...
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The present study investigated the antioxidant activity, metal chelating ability and genopro-tective effect of the hydroethanolic extracts of Crocus sativus stigmas (STG), tepals (TPL) and leaves (LV). We evaluated the antioxidant and metal (Fe 2+ and Cu 2+) chelating activities of the stigmas, tepals and leaves of C. sativus. Similarly, we examined the genotoxic and DNA protective effect of these parts on rat leukocytes by comet assay. The results showed that TPL contains the best polyphenol content (64.66 μg GA eq/mg extract). The highest radical scavenging activity is shown by the TPL (DPPH radical scavenging activity: IC50 = 80.73 μg/mL). The same extracts gave a better ferric reducing power at a dose of 50 μg/mL, and better protective activity against β-carotene degradation (39.31% of oxidized β-carotene at a 100 μg/mL dose). In addition, they showed a good chelating ability of Fe 2+ (48.7% at a 500 μg/mL dose) and Cu 2+ (85.02% at a dose of 500 μg/mL). Thus, the antioxidant activity and metal chelating ability in the C. sativus plant is important, and it varies according to the part and dose used. In addition, pretreatment with STG, TPL and LV significantly (p < 0.001) protected rat leukocytes against the elevation of percent DNA in the tail, tail length and tail moment in streptozotocin-and alloxan-induced DNA damage. These results suggest that C. sativus by-products contain natural anti-oxidant, metal chelating and DNA protective compounds, which are capable of reducing the risk of cancer and other diseases associated with daily exposure to genotoxic xenobiotics.
... Dysbiosis is typically described as an unbalanced microbial community that undergoes metabolic perturbations generally after dietary changes. Ruminal SCFA alternation, low pH and loss of diversity (Brown et al., 2012;Hawrelak & Myers, 2004) have been shown to negatively affect animal health by promoting the proliferation of opportunistic microbes and their products (Plaizier et al., 2008;Tao et al., 2017). A deep characterization of dysbiosis is thus important for its early diagnosis. ...
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Aim: This study aimed to characterize the critical points for determining the development of dysbiosis associated with feed intolerances and ruminal acidosis. Methods and results: A metabologenomics approach was used to characterize dynamic microbial and metabolomics shifts using the rumen simulation technique (RUSITEC) by feeding native cornstarch (ST), chemically-modified cornstarch (CMS), or sucrose (SU). SU and CMS elicited the most drastic changes as rapidly as 4 h after feeding. This was accompanied by a swift accumulation of D-lactate, and the decline of benzoic and malonic acid. A consistent increase in Bifidobacterium and Lactobacillus as well as a decrease in fibrolytic bacteria was observed for both CMS and ST after 24 h, indicating intolerances within the fiber degrading populations. However, an increase in Lactobacillus was already evident in SU after 8 h. An inverse relationship between Fibrobacter and Bifidobacterium was observed in ST. In fact, Fibrobacter was positively correlated with several short-chain fatty acids (SCFA), while Lactobacillus was positively correlated with lactic acid, hexoses, hexose-phosphates, pentose phosphate pathway (PENTOSE-P-PWY) and heterolactic fermentation (P122-PWY). Conclusions: The feeding of sucrose and modified starches, followed by native cornstarch, had a strong disruptive effect in the ruminal microbial community. Feed intolerances were shown to develop at different rates based on the availability of glucose for ruminal microorganisms. Significance of the study: These results can be used to establish patterns of early dysbiosis (biomarkers) and develop strategies for preventing undesirable shifts in the ruminal microbial ecosystem.
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Parkinson's disease (PD) is the second-most prevalent neurodegenerative or neuropsychi-atric disease, affecting 1% of seniors worldwide. The gut microbiota (GM) is one of the key access controls for most diseases and disorders. Disturbance in the GM creates an imbalance in the function and circulation of metabolites, resulting in unhealthy conditions. Any dysbiosis could affect the function of the gut, consequently disturbing the equilibrium in the intestine, and provoking pro-inflammatory conditions in the gut lumen, which send signals to the central nervous system (CNS) through the vagus enteric nervous system, possibly disturbing the blood-brain barrier. The neu-roinflammatory conditions in the brain cause accumulation of α-syn, and progressively develop PD. An important aspect of understanding and treating the disease is access to broad knowledge about the influence of dietary supplements on GM. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotic supplementation improves the function of the CNS, and improves the motor and non-motor symptoms of PD. Probiotic supplementation could be an adjuvant therapeutic method to manage PD. This review summarizes the role of GM in health, the GM-brain axis, the pathogenesis of PD, the role of GM and diet in PD, and the influence of probiotic supplementation on PD. The study encourages further detailed clinical trials in PD patients with probiotics, which aids in determining the involvement of GM, intestinal mediators, and neurological mediators in the treatment or management of PD.
Chapter
The gut microbiome is critical for overall human health. Many factors can disturb the gut microbiome and create dysbiosis. Both the mucous layer and the gut epithelial lining, which collectively serve as the gastrointestinal mucosal border, can be structurally degraded by gut dysbiosis. Increased intestinal permeability and compromised host resistance can ensue. Since all mucosal tissues in the body participate in cross-talk, other organ systems can be affected according to genetic predispositions and an increase in systemic chronic inflammation. The manifestation of named chronic diseases is the ultimate outcome. In this case, symptoms of various chronic diseases must be addressed. Specifically, periodontal disease, which is a chronic disease, must be understood and treated appropriately because it can become a second nidus of infection along with the primary nidus emanating from gut dysbiosis. However, the mystery of treatment does not only require medical intervention, although medical treatment for acute disease is critical. Essential treatment for this scenario usually includes a dietary and lifestyle solution to restore healthy gastrointestinal tract function. Unraveling the mystery of treatment involves introducing viable probiotics and prebiotics; removing elements of an inflammatory diet; providing necessary nutrients and nourishment for cellular function, eliminating toxic elements and chemicals; and creating a healthy lifestyle of stress reduction, restorative sleep, and efficient exercise.
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Gut microbial communities are vital for maintaining host health, and are sensitive to diet, environment, and chemical exposures. Wastewater treatment plants (WWTPs) release effluents containing antimicrobials, pharmaceuticals, and other contaminants that may negatively affect the gut microbiome of downstream organisms. This study investigated changes in the diversity and composition of the digestive gland microbiome of flutedshell mussels (Lasmigona costata) from upstream and downstream of two large (service >100,000) WWTPs. Mussel digestive gland microbiome was analyzed following the extraction, PCR amplification, and sequencing of bacterial DNA using the V3-V4 hypervariable regions of the 16 S rRNA gene. Bacterial alpha diversity decreased at sites downstream of the second WWTP and these sites were dissimilar in beta diversity from sites upstream and downstream of the first upstream WWTP. The microbiomes of mussels collected downstream of the first WWTP had increased relative abundances of Actinobacteria, Bacteroidetes, and Firmicutes, with a decrease in Cyanobacteria, compared to upstream mussels. Meanwhile, those collected downstream of the second WWTP increased in Proteobacteria and decreased in Actinobacteria, Bacteroidetes, and Tenericutes. Increased Proteobacteria has been linked to adverse effects in mammals, but their functions in mussels is currently unknown. Finally, effluent-derived bacteria were found in the microbiome of mussels downstream of both WWTPs but not in those from upstream. Overall, results show that the digestive gland microbiome of mussels collected upstream and downstream of WWTPs differed, which has implications for altered host health and the transport of WWTP-derived bacteria through aquatic ecosystems.
Chapter
The gut microbiota is the community of microbes (bacteria, viruses, fungi) that live in the gastrointestinal tract and are critical for normal nutrient absorption, digestion, and immune system development. These microbes communicate with the central nervous system (CNS) through interactions with the immune system, production of neuroactive metabolites/neurotransmitters, and activation of the vagus nerve. Spinal cord injury (SCI) disrupts the autonomic nervous system (ANS) and impairs communication with organ systems throughout the body, resulting in dysautonomia. This dysautonomia contributes to the pronounced immunosuppression and gastrointestinal dysfunction seen after SCI. Combined with frequent antibiotic use, physical and psychosocial stress, and altered GI motility, SCI-induced dysautonomia likely also causes an imbalance in the composition of the gut microbiome, i.e., gut dysbiosis. Pre-clincal and clinical studies indicate that SCI-induced gut dysbiosis triggers intestinal inflammation, impairs gut motility, and alters the composition of serum metabolites. SCI not only affects the abundance of various gut microbes but also the functional potential of the gut microbiome. As gut dysbiosis develops and the metabolites produced by gut microbiota change, these changes can influence the progress or severity of various SCI-associated comorbidities including metabolic syndrome, cardiovascular disease, liver dysfunction, and depression/anxiety disorders. Therefore, the development of novel therapeutic targets to prevent and treat these comorbidities requires a better understanding of how SCI affects the emergence or reduction in key gut microbial species.
Article
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.
Chapter
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.