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Clinical Studies Evaluating Effects of Probiotics on Parameters of Intestinal Barrier Function


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The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can, strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or ani-mal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans. Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with pro-biotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating a clear potential of probiotics in this field. In a case series of 14 patients using Ecologic â 825, a probiotic food supple- ment with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly. Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin might be valuable markers to measure epithelial barrier function in future experiments.
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Advances in Microbiology, 2013, 3, 212-221
doi:10.4236/aim.2013.32032 Published Online June 2013 (
Clinical Studies Evaluating Effects of Probiotics on
Parameters of Intestinal Barrier Function
Saskia van Hemert1*, Jurre Verwer1, Burkhard Schütz2
1Winclove Probiotics, Amsterdam, the Netherlands
2Biovis Diagnostik MVZ GmbH, Limburg-Offheim, Germany
Email: *
Received March 6, 2013; revised April 4, 2013; accepted May 4, 2013
Copyright © 2013 Saskia van Hemert et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut
into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can,
strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or ani-
mal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans.
Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier
function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with pro-
biotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but
patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among
these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating
a clear potential of probiotics in this field. In a case series of 14 patients using Ecologic825, a probiotic food supple-
ment with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly.
Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the
markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin
might be valuable markers to measure epithelial barrier function in future experiments.
Keywords: Bacteria; Epithelial Barrier; Gut Permeability; Intestinal Barrier Function; Intestinal Integrity; Probiotics;
Review; Vivo Studies
1. Introduction
The intestinal epithelial cells have a dual function. On
one hand they facilitate absorbance and transport of nu-
trients, electrolytes and water. On the other hand they
also form a barrier between the body and the bacteria,
toxins and antigens present in the gut. The ability to con-
trol the invasion of harmful content from the lumen to
the body is called the intestinal barrier function. This
defense mechanism consists of multiple elements, like
the mucous layer, secretory IgA, antimicrobial peptides,
and the apical junction complex. The latter is composed
of tight junctions, adherence junctions and desmosomes.
The tight junctions seal the paracellular pathway and are
the rate-limiting step in the transport between adjacent
epithelial cells [1].
The intestinal barrier can be disturbed by various causes,
like certain medicines, exercise, mast cell activation, high
fat diet, stress, etc. [1]. This can lead to an increased per-
meability, allowing amongst others enhanced entrance of
lipopolysaccharides (LPS) into the body. LPS are parts of
the outer membrane of Gram-negative bacteria and are
strong endotoxic compounds. They can cause the release
of pro-inflammatory cytokines in the body, leading to
inflammation. Increased permeability of the epithelial bar-
rier has been associated with many gastrointestinal in-
flammatory disorders, like inflammatory bowel diseases
(IBD, Crohn’s disease and ulcerative colitis), irritable
bowel syndrome (IBS), food allergies and celiac disease
[2]. In addition, increased permeability can also lead to
systemic inflammatory diseases, like allergy, metabolic
syndrome, diabetes, atherosclerosis, chronic fatigue syn-
drome, autism, migraine and rheumatoid arthritis [3].
Probiotics are living microorganisms that have benefi-
cial effects on the health of the host [4]. Strains docu-
mented as probiotic tend to be species of Lactobacillus or
*Corresponding author.
Copyright © 2013 SciRes. AiM
S. van HEMERT ET AL. 213
Bifidobacterium. More and more is known that probiotic
effects are species- and even strain-specific. Certain pro-
biotics have shown to be effective in different gut-related
diseases, like antibiotic-associated diarrhea and necrotiz-
ing enterocolitis in premature infants [5,6]. For some
other diseases, including IBD the effects of probiotics are
promising, but so far results from clinical trials have
been inconsistent [7]. Probiotics have proven strain-de-
pendent capabilities in vitro as well as in vivo to improve
the epithelial barrier function via different mechanisms
[8,9]. Most work has been done in cell culture systems or
in animal models [9-11]. Effects in humans are difficult
to measure in vivo due to the inaccessibility of the intes-
tine. One way to overcome this problem is by oral ad-
ministration of test substances and measurement of uri-
nary excretion. The lactulose/mannitol (L/M) test or a
comparable sugar test is the most used method to meas-
ure intestinal permeability. Lactulose is a disaccharide
which is passively absorbed through the paracellular path-
way via the tight junctions. Mannitol, which is a mono-
saccharide, is transported via the transcellular pathway.
In the case of heightened permeability, more lactulose
passes the barrier and eventually ends up in the urine.
Therefore, a high lactulose/mannitol ratio represents a
high, i.e. pathological, intestinal permeability. Other test
substances that are used, are 51Cr-EDTA or polyetylene
glycols (PEG). The 51Cr-EDTA test has been used to
detect increased intestinal permeability in Crohn’s Dis-
ease, celiac disease, and non-alcoholic fatty liver disease
[12-14]. Urinary excretion of PEG was significantly
higher in patients with alcoholic liver disease and with
acute pancreatitis compared to healthy controls [15,16].
Disadvantages are that all these methods are not very
sensitive, and that they are affected by intestinal transit
and the renal elimination rate [16]. Alternatively, other
biomarkers for intestinal permeability are sometimes meas-
ured, like intestinal fatty acid binding protein (IFABP),
C-reactive protein (CRP), tumor necrosis factor α (TNF-
α), alpha1-antitrypsin, calprotectin, eosinophil cationic
protein (ECP) and zonulin [17,18]. These biomarkers have
been correlated with barrier function, but do not measure
it directly. IFABP is a protein specifically located in the
apical villi of small bowel mucosa that is released into
the systemic circulation in the event of enterocyte death
and is a marker for enterocyte damage and intestinal
ischemia [19,20]. CRP, TNF-α and ECP are general mar-
kers for inflammation, whereas α1-antitrypsin and cal-
protectin are markers for intestinal inflammation. Zonulin is
a relatively novel marker of permeability [3]. It is a phy-
siologic modulator of the intercellular regulation of tight
junction proteins and thereby the paracellular epithelial
intestinal permeability [21-23]. Moreover, the intestinal
permeability can also be assessed by measuring the bac-
terial translocation (BT) through analysis of mesenteric
lymph nodes (MLN) or blood plasma by quantitative or
qualitative PCR.
In this review an overview of human studies is given
in which effects of probiotics on the intestinal barrier
function are investigated. Also a case series with Ecolo-
gic®825 is described, a potential probiotic product which
has shown positive effects on epithelial barrier function
in both a cell culture system (Saskia van Hemert, per-
sonal communication), as well as in a rat model of chronic
water avoidance stress [24].
2. Material and Methods
2.1. Literature Review
The systematic literature search was conducted in Pub-
Med up to 1 January 2013, using the following (truncated)
keywords “probiotic*, lactobacill* or bifidobact* AND
trial AND barrier or permeability”. A second search was
performed with “probiotic*, lactobacill* or bifidobact*
AND epithelial barrier, intestinal integrity or tight junc-
tions”. The search was limited to full-text English written
papers. This resulted in 205 hits. By screening the titles
and abstracts, studies performed in vitro, in animals and
reviews were subsequently excluded. Full text of the re-
maining 25 papers was checked. Additional papers were
found by checking references of pertinent articles and by
searching on “probiotic*” and different methods of meas-
uring intestinal permeability.
2.2. Case Series
In the case series 14 patients, 3 male and 11 female, be-
tween 18 and 65 (mean 46) years of age were included in
September 2011. The participants were informed by their
physician and gave their informed consent to the physi-
cian. All procedures were in accordance with the Hel-
sinki Declaration of 1975. Exclusion criteria were known
inflammatory gastrointestinal diseases, use of probiotics
or antibiotics four weeks prior to the study, use of gastric
acid inhibitors, presence of known diabetes type II and
pregnancy. The patients were supplemented with a daily
dose of >7.5 × 109 cfu Ecologic®825 (Winclove Probiot-
ics) for 8 weeks. Ecologic®825 is a food supplement con-
taining a mixture of 9 bacterial strains: Bifidobacterium
bifidum W23, Bifidobacterium lactis W51, Bifidobacte-
rium lactis W52, Lactobacillus acidophilus W22, Lacto-
bacillus casei W56, Lactobacillus paracasei W20, Lac-
tobacillus plantarum W62, Lactobacillus salivarius W24
and Lactococcus lactis W19. Before the start of the sup-
plementation (t = 0 weeks) and at the end (t = 8 weeks)
blood serum and faeces samples were collected to deter-
mine parameters for impaired barrier function.
2.3. Analyses
Zonulin, α1-antitrypsin and calprotectin in stool samples
Copyright © 2013 SciRes. AiM
were analyzed with commercially available ELISA kits
(Immundiagnostik AG, Bensheim, Germany) as described
earlier [25]. In the serum levels the following parameters
were measured with standard procedures (Biovis Diag-
nostik): IgG4 antibodies against banana, egg, hazelnut,
cow milk, soy beans and wheat, and high sensitive
(hs)CRP. IgG4 antibodies were measured by DST Ag
Schwerin and the hsCRP on Siemens Immulite 2000. A
lactulose/mannitol test was performed by giving the pa-
tients a mixture of 30 mg mannitol and 150 mg lactulose
stirred into 50 mL non-carbonated mineral water. Urine
samples were analysed by applying the HPLC method of
Immuchrom GmbH Heppenheim.
2.4. Statistics
For the case series, a paired student t-test was used to
measure the significance of the parameters before and
after the intervention period. Differences were consi-
dered significant at 2-tailed p < 0.05.
3. Results and Discussion
3.1. Literature Study
In total 29 studies were found by systemic literature
search, which investigated the effect of a single bacterial
strain or a bacterial mixture on the human intestinal bar-
rier function in vivo (Tables 1 and 2). This was often a
secondary endpoint, as the primary endpoint in most
cases was a decrease in a clinical endpoint. More than
half of the studies (17/31) showed a positive effect of the
used probiotics on epithelial barrier function, whereas the
other studies (13/31) did not show an effect. One study
had two arms and a placebo whereby a positive effect
was found in only one of the arms [26]. In general, the
study groups were small, ranging from 4 to 81 persons
per group. For some studies the small numbers of par-
ticipants might be an explanation for the fact that no sig-
nificant effects were found, for example the study of Al-
berda et al., showed a trend (p = 0.06) with groups of 7
patients only [28]. Most studies (n = 20) had treatment or
alleviation of clinical symptoms as purpose, while a
small group of studies (n = 9) aimed for a preventive
effect [18,28-35]. This effect was sought for example in
preventing bacterial infections in infants, [33] or pre-
venting post-infectious complications [18,30-32,34]. At
first sight, the result consists of a very heterogeneous
assembly of investigations. This variety is reflected in a
number of factors related to the probiotics, to the patient
population and the methodology. The probiotics used in
the studies varied in daily dose, duration of supplementa-
tion and number and type of bacterial strains. The patient
population ranged from healthy volunteers to critically ill
patients and preterm infants. The use of medicines like
non-steroid anti-inflammatory drugs and antibiotics are
an additional factor of variation in the patient population.
There were also marked differences between the power
of the studies, methodological quality of the studies and
the analytical methods to measure intestinal barrier func-
tion. The heterogeneity found in this literature review, is
also found in other recent reviews summarizing for ex-
ample the role of probiotics in the treatment of eczema,
IBD and IBS [36-38]. The heterogeneity caused by the
probiotic regime, the patient population and the method-
ology of measuring epithelial barrier function will be
discussed below.
3.1.1. Probiotic Regime
One of the variables related to the used probiotics is the
daily dose. This ranged from 1 × 109 colony forming
units (CFU) [28] to 1 × 1012 CFU [35] of the studies
yielding positive effects and from 1 × 109 CFU [39] to 9
× 1011 CFU [27] of the studies with no clear benefit on
barrier function. When looking at the mean daily dose,
the positive studies administered on average 1 × 1011
CFU, while the studies without positive effects used 8 ×
1010 CFU, a negligible difference on the log-scale used to
determine the CFU. Also the medians were very similar,
1 × 1010 CFU in both groups. These results imply that a
relatively high dose is not principally necessary to result
in a positive effect nor does it give any guarantee of such.
Moreover, different patient groups might benefit from
different daily doses to elicit effects.
The duration of supplementation in the studies also
varied strongly, from 1 [35] to 183 days [40] in the posi-
tive studies and from 2 [41] to 92 day [42] in the studies
without an effect. The mean durations were 40 vs. 28
days for studies with a positive effect and no effect re-
spectively, whereas the medians were 28 days for both
groups of studies. Some authors suggested that the lack
of a positive outcome was due to a too short intervention
duration [31,43]. However other longer studies did not
find any positive effect as well [42,44]. One interesting
finding is the loss of the beneficial effect over time. In
the study of Gupta et al. [40] a positive effect on intesti-
nal permeability was found after 12 weeks, but this effect
was lost after 24 weeks, despite a supplementation during
24 weeks. Finally, studies were also checked for a fol-
low-up period, to speculate on the persistence of a bene-
ficial effect of probiotics. Only two studies specifically
defined a follow-up test but neither of both tested the
intestinal permeability at that time [45,46]. Although the
clinical symptoms remained lower in the probiotics group,
nothing can be said about the persistent effects on intes-
tinal permeability.
From in vitro studies it is already known that bacterial
strains can vary considerably on their effects on epithe-
lial barrier function [8,47]. Also the studies in this review
Copyright © 2013 SciRes. AiM
Copyright © 2013 SciRes. AiM
aAT = α1-antitrypsin; BT = bacterial translocation; C = cellobiose; CRP = C-reactive protein; IFABP = intestinal fatty acid binding protein; L = lactulose; LPS = lipopolysacchariden; M = mannitol; PEG = poly eth-
ylene glycol; sCD14 = soluble CD14; TJ = tight junction; bB = Bifidobacterium; E = Enterococcus; L = Lactobacillus; Lc = Lactococcus; Leuc = Leuconostoc; LGG = Lactobacillus rhamnosus GG; P = Propionibac-
S = Stre
n.d. = not
Table 1. Studies with probiotics showing an improvement in epithelial barrier function.
aAT = α1-antitrypsin; BT = bacterial translocation; C = cellobiose; CRP = C-reactive protein; IFABP = intestinal fatty acid binding protein; L = lactulose; LPS = lipopolysacchariden; M = mannitol; PEG = poly eth-
ylene glycol; sCD14 = soluble CD14; TJ = tight junction; bB = Bifidobacterium; E = Enterococcus; L = Lactobacillus; Lc = Lactococcus; Leuc = Leuconostoc; LGG = Lactobacillus rhamnosus GG; P = Propionibac-
terium; S = Streptococcus.
Table 2. Studies with probiotics not showing an improvement in epithelial barrier function.
Copyright © 2013 SciRes. AiM
Copyright © 2013 SciRes. AiM
used a variety of strains whereby L. rhamnosus (mainly
LGG) and L. plantarum were the most used species.
Strain selection is an important point in the design of
studies with probiotics as the effects can vary largely
between strains. It has been suggested that multispecies
probiotic products (products with multiple strains, pref-
erentially of different genera) are in general more effec-
tive compared to monospecies products (containing a
single strain) [48,49], but for the studies in this review
the results were comparable for monostrain and multis-
pecies products. Monostrain products were used in 10
studies with a positive outcome and 8 studies without a
beneficial effect on barrier function, whereas multispe-
cies products were involved in 8 studies with a positive
outcome and 7 studies without beneficial effect. How-
ever, for the large majority of the studies it was not de-
scribed how the used strains were selected or why these
specific strains were used.
3.1.2. Patient Groups
Another point of interest is the variation of patient groups
in the studies reviewed. While patients with atopic ec-
zema/dermatitis suffer from inflammatory processes lead-
ing to or even might be caused by barrier dysfunctions in
the skin and gut, the clinical manifestation in acute pan-
creatitis or other critically ill patients is quite different.
Different pathological mechanisms can lead to various
problems with the epithelial barrier, perhaps requesting
diverse probiotic approaches.
3.1.3. Measurement of Intestinal Permeability
Besides heterogeneity in the bacterial strains and the pa-
tient group, the method of measuring the intestinal per-
meability was a third source of heterogeneity. While the
majority of the studies used a sugar absorption test (19
out of 29), the used sugars were variable (lactulose, man-
nitol, cellobiolose, sucrose or rhamnose). Other methods
were PEG and in some studies tight junction protein
staining was used. IFABP or IgA/IgG were additionally
measured in some studies [17,18,50] as indirect indices
of the epithelial barrier integrity. CRP, TNF-α, α1-anti-
trypsin, mesenteric lymph nodes biopsies and PCR were
often used to assess inflammatory and/or bacterial activ-
ity or translocation. Measuring bacterial translocation to
the mesenteric lymph nodes can only be done in studies
with operations. This method does not seem to correlate
with results of a sugar test [51] and it has been suggested
that bacterial translocation after abdominal surgery may
be part or normal antigen-sampling processes of the gut
[18]. The two studies with HIV-infected individuals both
used PCR on blood plasma to determine microbial trans-
location, whereas this method has not been used in any of
the other studies with probiotics. Whereas this method is
relevant to measure intestinal barrier function remains to
be determined, as liver function might also influence the
levels of bacterial DNA in blood plasma. A relatively
novel marker of barrier function is zonulin, which was
used in a recent study with probiotics [25]. Zonulin has
been suggested as one of the most valid surrogate mark-
ers to estimate intestinal barrier function in humans [52].
There is no evidence that one specific method is more
sensitive than another. In studies using the L/M ratio an
effect was not found more often than studies using other
sugar tests. However, in all studies using PEG no effect
was observed [17,18,53]. Interestingly in one study ef-
fects of probiotic supplementation on plasma levels of
LPS were observed, despite a lacking effect as measured
with PEG [53]. Although the L/M test or a comparable
sugar test was often used, this method had some draw-
backs. First, due to the lack of a standardization [54], the
L/M ratio varies considerably even among healthy indi-
viduals. Indeed, the investigators of the current articles
differ in their normal values of the L/M ratio regarding
what is physiological and pathological. Second, the
quantity of sugars used varied from 250 mg to 10 g for
lactulose and from 100 mg to 5 g for mannitol. Although
the absolute quantities used might not be of major influ-
ence, as the eventual ratio is a relative value, the osmo-
larity of the test solution can have influenced the out-
comes [54]. Other methods to measure intestinal perme-
ability are 51Cr-EDTA and 99mTcDTPA, which are non-
degraded radio-labeled chelates used to measure intesti-
nal permeability [55], but so far they have not been used
by studies with probiotics.
3.2. Case Series
To investigate which parameters are useful to measure in
relation to probiotics and epithelial barrier function, we
measured different parameters related to barrier function
in a case series of 14 patients.
Zonulin levels in faeces were elevated (>30 ng/ml) in
10 of the 14 people participating in the case series before
the start of the intervention. The average zonulin levels
decreased significantly after the 8 weeks intervention
period (p < 0.01, Figure 1(a)). In the group of people
started with elevated zonulin levels, the levels decreased
in 8 of the 10 persons during the intervention period. In
the control group 2 of the 4 persons showed decreased
zonulin levels after 8 weeks of intervention. Alpha1-
antitrypsin levels were elevated in 7 out of the 14 people
before the start of the intervention period (>27.2 mg/dl)
and it decreased significantly after the intervention (p <
0.01, Figure 1(b)). These levels were decreased in 6 of
the 7 people starting with elevated levels, and also in 6 of
the 7 people starting with levels in the normal range
(<27.2 mg/dl). Interestingly the person who started with
elevated levels of alpha1-antitrypsin, but didn’t show a
Figure 1. Effect of 8 weeks supplementation with Ecologic825 on the average levels of (a) zonulin; (b) α1-antitrypsin and (c)
hsCRP. Normal values are indicated with a dotted line. The average values are indicated in bold .
decrease also did not show a decrease in zonulin. The
three persons who had the highest zonulin levels before
the start of the study also had the highest alpha1-anti-
trypsin at the start. High sensitive CRP was measured in
only 9 people, due to technical problems. The levels were
elevated in 5 of the 9 people before the start of the trial
(>0.55 mg/l). Those levels were decreased in all five par-
ticipants which had elevated levels before the start of the
intervention, but not in the persons which started with
normal values (Figure 1(c)). The IgG4 antibodies against
food allergens (measured in 9 of the 14 people) did not
show any differences before and after the intervention
(results not shown). Calprotectin levels were in all cases
under the detection limit of 10 mg/l. In addition there
were also no differences found with the L/M test.
The participants in these case series visited their phy-
sician due to gastrointestinal complaints. In our study
elevated levels of three markers of intestinal permeability
were found in the majority of the participants. These
markers were zonulin, α1-antitrypsin and CRP. In this
cases series, zonulin levels were measured in faeces, as
was also done in a study investigating the effects of pro-
biotic supplementation in trained men [24]. Measure-
ments of zonulin have also been performed is intestinal
tissue and serum. Tissue levels of zonulin in the intestine
were much higher in celiac patients compared to controls
[21]. Higher levels of zonulin in serum correlate with
higher intestinal permeability as measured with the L/M
test [56,57]. This is in contrast with our study, where no
abnormal L/M ratio was measured while we did find
changes in zonulin levels. This might indicate that zonu-
lin is a more sensitive marker of intestinal barrier func-
tion than the L/M test.
Alpha1-antitrypsin is a marker used as a measure of
protein leakage into the intestinal tract and for inflamma-
tion in individuals with IBD [58]. In the case series a
significant decrease in the levels of α1-antitrypsin in fae-
ces was detected. A similar decrease of levels of α1-an-
titrypsin was found in a study with probiotics in children
with cow-milk allergy [26], but not in a study with pro-
biotics in trained men [25]. This latter finding might be
due to the fact that the α1-antitrypsin levels were not
elevated before the start of the study in the study popula-
tion, whereas this was the case in the described case se-
ries and the study of Viljanen et al. [26]. As inflamma-
tion is linked to impaired intestinal barrier function [59]
it is not surprising that a marker for inflammation might
also be valuable as a marker for barrier function. Faecal
calprotectin is, similar as α1-antitrypsin, used as marker
in IBD [60], but the levels of calprotectin were below the
detection limit of 10 mg/L in the studied patient group.
This might indicate that in contrast to α1-antitrypsin,
calprotectin is not a useful marker for subtle intestinal
barrier problems, but more relevant in diseases like IBD
with marked inflammation of the epithelial barrier func-
tion. Another marker for inflammation is CRP, which
was also identified in the case series. In another study
CRP tended to be higher in obese patients compared with
healthy weight controls [61]. CRP levels were associated
with certain faecal metabolites and were inversely corre-
lated with the total microbial counts, indicating a possi-
ble influence of the gut microbiota on CRP levels. Ele-
vated CRP levels were correlated with enhanced L/M
ratios in some studies [62,63], but not in all [64]. This
suggests that increased levels might be caused by en-
hanced intestinal permeability, but can also have other
causes. These elevated levels of CRP might indicate a
systemic response to increased LPS in the body due to an
enhanced permeability of the gut. From that perspective,
CRP is not a direct measurement of intestinal permeabil-
ity, but is probably more an indirect measurement.
3.3. Wider Implications
The primary aim of this narrative review was to provide
Copyright © 2013 SciRes. AiM
S. van HEMERT ET AL. 219
an intensive overview of the current literature regarding
the influence of probiotics on the human intestinal barrier
function. This review is, to our knowledge, the first to
overview the literature of probiotics and intestinal per-
meability in in vivo human studies. Overall, there are
several indications in vivo that probiotics can have posi-
tive effects on the barrier function, as a positive effect
was found in 48% of the controlled studies. The hetero-
geneity of the studies makes it impossible to draw any
conclusions on probiotic treatment specifications. It is
plausible that different patient groups might benefit from
different treatment plans, such as daily dose, strain and
duration. Moreover, different disturbances of the gut bar-
rier might also ask for different barrier measurements.
The case series indicated that zonulin, α1-antitrypsin and
hsCRP might be valuable markers to measure intestinal
permeability in vivo. Clearly, more investigations have to
be conducted to draw strong conclusions. For these in-
vestigations consensus is necessary on standardized meth-
ods to measure barrier function.
4. Acknowledgements
The authors like to thank the participants of the case se-
ries for their participation in the study.
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... In the last years of the old century and the beginning of the new one, the discovery that our gastrointestinal tract is home to a huge number of beneficial bacteria, known as intestinal microflora, changed the understanding of many physiological and pathological processes in the human body. [1] Microbiota is the common name for intestinal microflora. The human microbiome is a collection of all genes contained in the microbiota. ...
... This synergistic combination supports the repair of inflamed intestinal mucosa caused by prolonged stress and mental strain by restoring the barrier function of the intestine [1]. ...
Full-text available
Background: In the last years of the old century and the beginning of the new century, the discovery that our gastrointestinal tract is home to a huge number of beneficial bacteria known as intestinal microflora changed the understanding of many physiological and pathological processes in the human body. Based on these scientific discoveries, the laboratories of the Allergozan Institute in Austria have created the synbiotic combinations "Omnibiotic", which are specific and aimed at specific problems related to human health. Purpose: The aim of the present study is to investigate the effect of the probiotic Omni Biotic Stress Repair in the treatment of functional abdominal pain (FAP) and some organic gastrointestinal diseases in childhood. Material and Methods: A prospective study has been done on children with FAP and PUD. For one year, we monitored 62 children with functional abdominal pain and duodenal ulcer who received Omni Biotic Stress Repair for 3 months. The causes of children's suffering were reported. Results: There are 39 children with functional abdominal pain, 22 of which are girls and 17 boys, and children with peptic ulcer disease – 23/12 boys and 11 girls/. The FAP group received Omni Biotic Stress Repair as self-therapy for three months. We reported very good results in all children. Only four children did not get the desired effect, and they dropped out of the study in the first month. In children with peptic ulcer disease, the probiotic Omni Biotic Stress Repair is added as a satellite therapy to the main treatment. When clinical remission occurred, the patients continued to take only probiotics for 3 months or more. Conclusions: Based on these scientific discoveries, the laboratories of the Allergozan Institute in Austria have created the synbiotic combinations "Omnibiotic", which are specific and aimed at specific problems related to human health.
... This is a significant problem as it may affect up to 20-60% of competitors performing intense physical activity (training for around 4-6 h a day, 6 days a week, thus not allowing the body to regenerate) [9]. The intestinal barrier, which is essential for protecting the host against invading pathogens, also plays a crucial role in maintaining overall health [10]. The intestinal barrier can be adversely affected by great (≥60-70% VO 2max ) physical exertion (the circulatory-gastrointestinal pathway redistributes blood flow to working muscles and peripheral circulation, thus reducing total splanchnic perfusion, and the neuroendocrine pathway enhances sympathetic activation results in reduced the functional capacity of the GI system) and medication, in particular nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs), as well as chronic stress (also associated with participation in sporting competitions) [10,11]. ...
... The intestinal barrier, which is essential for protecting the host against invading pathogens, also plays a crucial role in maintaining overall health [10]. The intestinal barrier can be adversely affected by great (≥60-70% VO 2max ) physical exertion (the circulatory-gastrointestinal pathway redistributes blood flow to working muscles and peripheral circulation, thus reducing total splanchnic perfusion, and the neuroendocrine pathway enhances sympathetic activation results in reduced the functional capacity of the GI system) and medication, in particular nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs), as well as chronic stress (also associated with participation in sporting competitions) [10,11]. ...
Full-text available
As many as 70% of athletes who practice endurance sports report experiencing gastrointestinal (GI) symptoms, such as abdominal pain, intestinal gurgling or splashing (borborygmus), diarrhea or the presence of blood in the stool, that occur during or after intense physical exercise. The aim of the study was to evaluate the effect of a multi-strain probiotic on the incidence of gastrointestinal symptoms and selected biochemical parameters in the serum of long-distance runners. After a 3-month intervention with a multi-strain probiotic, a high percentage of runners reported subjective improvement in their general health. Moreover, a lower incidence of constipation was observed. In the group of women using the probiotic, a statistically significant (p = 0.035) increase in serum HDL cholesterol concentration and a favorable lower concentration of LDL cholesterol and triglycerides were observed. These changes were not observed in the group of men using the probiotic. Probiotic therapy may reduce the incidence and severity of selected gastrointestinal symptoms in long-distance runners and improve subjectively assessed health condition.
... Anabrees 2014). Besides, probiotics can help maintain intestinal barrier integrity (Hemert et al. 2013). Moreover, probiotic administration can protect and enhance the gut microbiota of mice by improving the number of beneficial bacteria while decreasing the number of pathogenic bacteria (Li et al. 2019). ...
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Outbreaks of carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae (CRKP), are commonly reported as severe infections in hospitals and long-term care settings, and their occurrence is increasing globally. Conventional antibiotics used for treating CRE have become ineffective due to resistance development. Furthermore, their safety issues restrict their availability and use for CRE treatment. Therefore, developing new drugs different from existing drugs to combat this deadly menace is urgently needed. Probiotics can be a potential option in this context, as probiotics’ efficacy against a variety of infectious illnesses has already been well established. Here, we report the effect of the Bacillus velezensis strain isolated from Gochang Bokbunja vinegar in Korea on CRE infection using two mouse models. Data showed that pretreatment with B. velezensis significantly reduced body weight loss and mortality of CRKP-infected mice in the preventive model. The oral administration of B. velezensis in a therapeutic model also decreased the mortality and illness severity in CRKP-infected mice. Moreover, a two-week oral acute toxicity assay in guinea pigs did not reveal any aberrant clinical signs. Our findings demonstrate the potential effectiveness of our candidate probiotic strain, B. velezensis , against CRKP, suggesting that it could be used as an antimicrobial agent for treating CRKP-related infections.
... Probiotics have been associated with increased gut barrier integrity and reduced permeability; this was thought to occur due to increased mucin expression and tight-junction stability that protects the epithelial barrier (Stoidis et al., 2011;Hemert et al., 2013). Consequently, probiotic interventions can reduce endotoxemia and inflammation levels. ...
Full-text available
Introduction: Oral consumption of probiotics can alter Gut Microbiota by causing changes in the production of probiotic derivatives. Therefore, by utilizing Gut-Brain-Axis (GBA), probiotics could provide an opportunity for central nervous system (CNS) modulation, including cognitive function. Tempeh is a traditional Indonesian food rich in probiotics and beneficial for cognitive function. However, the type of probiotics that play a role in cognitive improvement and the number of probiotics needed for the benefits of increasing cognitive function was unknown. Method: This experimental study involved a total of 93 subjects, divided into 3 groups: A, B and C/control (n: 33, 32, and 28), who were provided with probiotic supplementation isolated from tempeh for 12 weeks intervention. Inclusion criteria were age > 60 years, and memory impairment with the third repetition value of Word List Memory Immediate Recall (WLMIR) < 7. Subjects with diabetes were excluded. Cognitive function examinations were carried out before and after treatment. The tempeh-derived probiotics were prepared trough several processes. Genomic isolation, detection of GABA-encoding genes, and species identification using the 16S-rRNA gene encoding were performed. Results: The probiotics isolate used in the intervention was identified as Limosilactobacillus fermentum. We assigned this isolate as L. fermentum A2.8. The presence of the gene encoding GABA was found on this isolate. There was an increase in the cognitive domains of memory, learning process, and verbal fluency (p < 0.05) in group A (probiotics at concentration of 108 CFU/mL). Memory function, visuospatial, and verbal fluency improved (p < 0.05) in group B (probiotics at concentration of 107 CFU/mL). Only an increase in the memory domain was observed in the control group. Improvement of the learning process occurred only in group A (p = 0.006). Conclusion: Administration of probiotics derived from L. fermentum A2.8 increased the cognitive domains of memory, language and visuospatial function. However, probiotic supplementation at a concentration of 108 CFU/mL was better in improving the learning process. This study succeeded in detecting Lactic Acid Bacterial isolates L. fermentum A2.8 that enclosed gene encoding glutamate decarboxylase (gad) which is involved in the synthesis of -aminobutyric acid (GABA), a neurotransmitter vital for cognitive function.
... The intestinal microbiota can also be altered by drugs such as antibiotics but also by other factors such as advancing age, incorrect diet, and genetic predisposition of the host [237,238]. Therefore, to restore the correct intestinal flora, probiotic products can be used, as they have been shown to be effective in improving the barrier function of the intestinal epithelium, thus preventing the microbiota from passing into the circulation [239,240]. Probiotic supplementation had a beneficial effect on the lipid profile in obese post-menopausal women, who were given two different doses of Ecologic barrier, a multi-species probiotic product. The administration of the higher dose (1 × 1010 CFU per day) resulted in a greater reduction in glucose, insulin, and HOMA-IR levels when compared with administration of the lower dose. ...
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The importance of functional food and nutraceutical products to deal with cardiometabolic diseases (CMDs) and metabolic syndrome (MetS) has gained attention in the past few years. The aim of this narrative review is to highlight the potential and effectiveness of nutraceutical in the improvement of CMDs and MetS biomarkers, alongside their burden of disease and economic health expenditure. A science database search was conducted between May and June 2021. A total of 35 studies were included in this paper. We included male and female subjects, children, and adults, in good health or with cardiovascular or metabolic disease. CMDs and MetS have gradually become worldwide health problems, becoming two of the major causes of morbidity and mortality in western countries. The results indicate a positive link between daily consumption of nutraceutical products and an improvement in cardiometabolic and anthropometric biomarkers. In this paper we included a wide range of nutraceutical products. Most of them showed promising data, indicating that nutraceuticals could provide a new therapeutic treatment to reduce prevalence and pharmaceutical expenditures attributed to CMDs and MetS. Unfortunately, there is a huge vacuum of data on nutraceutical usage, savings, and burden reduction. Therefore, further clinical and pharmaco-economic research in the field is highly required.
... Probiotic supplementation improved markers of an intestinal barrier and inflammation in trained men under exercise stress in a randomised clinical trial (119), in rodents (120,121), and in a porcine intestinal epithelial cell line (IPEC-J2) (122). However, a systematic review from 2013 that included human studies measuring parameters of epithelial barrier function had evidence for and against probiotic supplementation (123). Note that the study population and probiotics employed were high in heterogeneity. ...
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Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.
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Probiotics give immunological protection to the host by regulating, activating, and modifying immune responses. Researchers are now focusing their efforts on better understanding the immunomodulatory effects of probiotics, which have the potential to prevent or ameliorate some diseases for which there is now no effective medical treatment. Immune cells (T-and B-cells) promote adaptive immunity and give immunological protection by developing pathogen-specific memory, according to scientific evidence. However, the purpose of this review is to highlight the most recent research on mechanism of probiotics and their immunomodulatory effects. It has been reported that a number of Lactobacillus and Bifidobacterium species have important roles in innate immunity by boosting natural killer cell cytotoxicity and macrophage phagocytosis, as well as mediating adaptive immunity by interacting with enterocytes and Th1, Th2, and Treg cells. Finally, the immunomodulatory effects of probiotics on the generation of proinflammatory and anti-inflammatory cytokines in various animal models have been thoroughly examined. Finally, this research goes through the immunomodulatory effects of probiotics on proinflammatory and anti-inflammatory cytokine production in several animal models. Isolating new probiotic strains and studying their immunomodulatory effects on cytokine profiles in people is therefore still a hot topic.
The intestine is the largest digestive and immune organ in the human body, with an intact intestinal mucosal barrier. Lactobacillus plantarum is an important strain of probiotics in the intestine for boosting intestinal immunity to defend against intestinal injury. In the lipopolysaccharide-induced intestinal injury model, mixed L. plantarum (L. plantarum KLDS 1.0318, L. plantarum KLDS 1.0344, and L. plantarum KLDS 1.0386) was suggested to boost intestinal immunity. In detail, compared with LPS-induced mice, mice in the mixed L. plantarum group showed significantly reduced intestine (jejunum, ileum, and colon) tissue injury, pro-inflammatory cytokine (TNF-α, IL-6 and IL-12) levels, myeloperoxidase activities, and serum D-lactate (P < 0.05) content. Moreover, the mixed L. plantarum significantly increased the number of immunocytes (CD4+ T cells, IgA plasma cells) and the expression of tight junction proteins (Claudin1 and Occludin). The results also showed that the mixed L. plantarum significantly down-regulated (P < 0.05) the intestinal protein expression of TLR4, p-IκB, and NF-κB p65. The mixed L. plantarum group increased the relative abundance of the genera, including Lactobacillus, Lachnoclostridium, and Desulfovibrio, which are related to improving the levels of SCFAs (acetic acid, butyric acid) and total bile acid (P < 0.05). Overall, these results indicated that the mixed L. plantarum had great functionality in reducing LPS-induced intestinal injury.
Leaky gut syndrome is characterized by increased intestinal permeability, translocation of compounds such as toxins, lipopolysaccharides and bacteria from the intestinal microbiota involving pro-inflammatory processes, metabolic changes, and imbalance of lipid and lipid homeotase recent research has related increased intestinal permeability to metabolic syndrome, which is characterized mainly by insulin resistance, abdominal obesity, lipid disorders, prothrombotic and pro-inflammatory processes. The objective of this study is to analyze through the literature review the pathophysiological mechanisms and factors involved in the relationship of Leaky gut syndrome and metabolic syndrome. The research included 113 scientific articles published between 2014 and 2021 in Medline/Pubmed, Scielo and Lilacs databases. Were selected, fifity original academic articles, written in English, which were analyzed according to the year of publication, evaluation method, objectives and main results. The increase in intestinal permeability and alteration of the intestinal microbiota involved inflammatory, lipidic processes, alterations in glucose homeostasis and secretion of enteroendocrine peptides among them GLUT2 and GLP-1 evidencing a strong relationship in pathophysiological mechanisms in Leaky Gut syndrome and metabolic syndrome. Even studies in humans is rare, there is an intense interrelationship between microbiota, altered intestinal permeability in Leaky Gut Syndrome and Metabolic Syndrome.
When taking a broader perspective on the societal impact of probiotics, engagement of end-users is important to discover unmet needs, define relevant health benefits and identify key considerations for successful implementation in daily practice. This study therefore takes a retrospective approach and analyses a database of user experiences to review the effects of four multispecies probiotic formulations. The user experiences were analysed in a dependent sample manner (without control group) and complement previous randomised controlled trials that have been performed with the formulations. The database consisted of 584 evaluable user experiences regarding the impact of probiotic supplementation on perceived quality of life (QoL), gastrointestinal (GIT) symptoms and reported stool consistency after two weeks of consumption. Two different scales were used (n=344 in a 5-point scale; n=240 in a 10-point scale), which are presented as separate analyses. In the combined population of the 5-point-scale questionnaire, a significant increase in perceived QoL and a significant reduction in perceived GIT symptoms was observed. Descriptive summaries also indicate that diarrhoea- and constipation-like stool patterns are reduced following supplementation. Moreover, half of participants indicated that probiotic supplementation had a positive effect on their unmet medical need, and 64% of users were likely to continue using the product. Similar results were observed in the 10-point scale questionnaire. Considering the clinical relevance of probiotic supplementation in specific target groups, subgroup analyses were performed on participants who consumed the products for diarrhoea, constipation, Inflammatory Bowel Disease, Irritable Bowel Syndrome, and antibiotic usage. Overall, findings support the potential of probiotics to advance perceived human health and support the daily wellbeing of users. This systematic analysis of user experiences thereby contributes to the external validity of studies evaluating clinical effects of probiotics and increases knowledge on their societal impact.
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Background HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production. Methods A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks. Results We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016). Conclusions Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources.
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Abstract Background Probiotics are an upcoming group of nutraceuticals claiming positive effects on athlete’s gut health, redox biology and immunity but there is lack of evidence to support these statements. Methods We conducted a randomized, double-blinded, placebo controlled trial to observe effects of probiotic supplementation on markers of intestinal barrier, oxidation and inflammation, at rest and after intense exercise. 23 trained men received multi-species probiotics (1010 CFU/day, Ecologic®Performance or OMNi-BiOTiC®POWER, n = 11) or placebo (n = 12) for 14 weeks and performed an intense cycle ergometry over 90 minutes at baseline and after 14 weeks. Zonulin and α1-antitrypsin were measured from feces to estimate gut leakage at baseline and at the end of treatment. Venous blood was collected at baseline and after 14 weeks, before and immediately post exercise, to determine carbonyl proteins (CP), malondialdehyde (MDA), total oxidation status of lipids (TOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Statistical analysis used multifactorial analysis of variance (ANOVA). Level of significance was set at p
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Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were up-regulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared to wild type UCC118. The wild type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, while a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.
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Background/objectives: Obesity and metabolic disorders are linked to inflammation via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. We intended to investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. Subjects/methods: Patients with MetS were randomized to receive 3 × 6.5 × 10⁹ CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels. Results: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. Conclusions: Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota.
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Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10(10) each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. Clinical NCT00688311.
The intestinal barrier serves 2 critical functions for the survival of the individual: first, it allows nutrient absorption and second, it defends the body from dangerous macromolecule penetration. It is a complex multilayer system, consisting of an external "anatomic" barrier and an inner "functional" immunological barrier. The interaction of these 2 barriers enables equilibrated permeability to be maintained. Many factors can alter this balance: gut microflora modifications, mucus layer alterations, and epithelial damage can increase intestinal permeability, allowing the translocation of luminal content to the inner layer of intestinal wall. Several techniques are now available that enable us to study gut permeability: "in vitro" models (Caco-2 and HT29-MTX cells) and "in vivo" not invasive tests (sugar tests and radioisotope scanning tests) are used to estimate permeability and to suggest molecular pathophysiological mechanisms of intestinal permeability in health and diseases. Many medicinal products used in the treatment of gastrointestinal diseases have also found to play an active role in modulate intestinal permeability: corticosteroids, 5-aminosalicylic acid, anti tumor necrosis factor, probiotics, and mucosal protectors, like gelatin tannate. This review will particularly address the role of the gut barrier in maintaining intestinal permeability (microbiota, mucus, and epithelial cells), the techniques used for estimating intestinal permeability and the therapeutic approaches able to modify it.
OBJECTIVES: To determine the relation between intestinal barrier dysfunction, bacterial translocation, and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes. SUMMARY OF BACKGROUND DATA: Randomized, placebo-controlled, multicenter trial on probiotic prophylaxis (Ecologic 641) in patients with predicted severe acute pancreatitis (PROPATRIA). METHODS: Excretion of intestinal fatty acid binding protein (IFABP, a parameter for enterocyte damage), recovery of polyethylene glycols (PEGs, a parameter for intestinal permeability), and excretion of nitric oxide (NOx, a parameter for bacterial translocation) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter. RESULTS: IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia (P = 0.03), infected necrosis (P = 0.01), and organ failure (P = 0.008). PEG recovery was higher in patients wh
Athletes exposed to high-intensity exercise show an increased occurrence of gastrointestinal (GI) symptoms like cramps, diarrhea, bloating, nausea, and bleeding. These problems have been associated with alterations in intestinal permeability and decreased gut barrier function. The increased GI permeability, a so-called 'leaky gut', also leads to endotoxemia, and results in increased susceptibility to infectious and autoimmune diseases, due to absorption of pathogens/toxins into tissue and the bloodstream. Key components that determine intestinal barrier function and GI permeability are tight junctions, protein structures located in the paracellular channels between epithelial cells of the intestinal wall. The integrity of tight junctions depends on sophisticated interactions between the gut residents and their expressed substances, the intestinal epithelial cell metabolism and the activities of the gut-associated lymphoid tissue. Probiotic supplements are an upcoming group of nutraceuticals that could offer positive effects on athlete's gut and entire health. Some results demonstrate promising benefits for probiotic use on the athlete's immune system. There is also evidence that probiotic supplementation can beneficially influence intestinal barrier integrity in acute diseases. With regard to exercise-induced GI permeability problems, there is still a lack of studies with appropriate data and a gap to understand the underlying mechanisms to support such health beneficial statements implicitly. This article refers (i) to exercise-induced intestinal barrier dysfunction, (ii) provides suggestions to estimate increased gut barrier permeability in athletes, and (iii) discusses the potential of probiotic supplementation to counteract an exercise-induced leaky gut.
The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal “leakiness.” Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD. (Inflamm Bowel Dis 2011;)