The offspring gestated in hypothyroxinemia has higher paracellular intestinal permeability and signs of intestinal inflammation

Background:Growing evidence argue for a role of the gut in the pathophysiology of various chronic rheumatic diseases such as spondyloarthritis (SpA). This so-called “gut-joint axis” involves dysbiosis, bacterial translocation, intestinal inflammation and increase in intestinal permeability. Recent data from clinical and basic research suggested that the integrity of the intestinal barrier might be a key determinant in translating autoimmunity to inflammation, making intestinal permeability a potential marker or a target for future therapies.Objectives:To analyse the available data on intestinal permeability in SpA patients and the effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal permeability.Methods:A systematic review was conducted. Without date restriction, the following databases were searched through September 1, 2020: Medline, Embase and Cochrane. Studies with patients with SpA assessing the intestinal permeability were selected. Some of the included studies have assessed the effect of NSAIDs on intestinal permeability.Results:A total of 12 studies were included in the final analysis. The 12 studies involved a total of 268 SpA patients, including 240 ankylosing spondylitis (AS). Among the studies included, four studies used the lactulose/mannitol test, four studies used the 51Cr-ethylenediaminetetraacetic test and two studies used the polyethylene glycols test. Nine of the 12 studies reported increased intestinal permeability regardless on the method used for intestinal permeability evaluation. Four studies evaluated the link between disease activity, assessed by CRP and ESR levels, and intestinal permeability and showed no correlation between increased intestinal permeability and markers of disease activity in AS patients. As regards the effects of NSAIDs on intestinal permeability, data are controversial. Two studies, including one evaluating indomethacin, did not show any influence of NSAIDs in AS patients, one study showed an increase in intestinal permeability under NSAIDs in only 60% of the patients, another study reported increased intestinal permeability. When comparing the effect of NSAIDs in patients with AS to healthy subjects, one study reported a comparable NSAIDs-induced increase in intestinal permeability in both groups.Conclusion:The results of our review suggest that increased intestinal permeability is present in SpA patients even in the absence of NSAIDs use and regardless of the method used to assess intestinal permeability. The effects of NSAIDs on intestinal permeability in SpA patients is more controversial and further studies are needed to clarify them.Disclosure of Interests:None declared

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Intestinal Barrier Function and Performance of Broiler Chickens Fed Additional Arginine, Combination of Arginine and Glutamine or an Amino Acid-Based Solution

Animals ◽

10.3390/ani11082416 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2416

Author(s):

Reza Barekatain ◽

Tristan Chalvon-Demersay ◽

Clive McLaughlan ◽

William Lambert

Keyword(s):

Amino Acid ◽

Intestinal Permeability ◽

Broiler Chickens ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Basal Diet ◽

Intestinal Barrier Function ◽

Glutathione Synthetase ◽

Feed Conversion ◽

Experimental Treatments

Two experiments were conducted to investigate the effect of arginine (Arg); the combination of Arg and glutamine (Gln); as well as an amino acid-based solution (MIX) containing Arg, Gln, threonine (Thr), and grape extract, on performance, intestinal permeability, and expression of selected mechanistic genes. Using 240 male Ross 308 off-sex broiler chickens, four experimental treatments were replicated six times with 10 birds per replicate. The experimental treatments included 5 g/kg Arg, 2.5 g/kg Arg and 2.5 g/kg Gln, and 1 g/kg MIX added to a basal diet as control. In the second study, the four dietary treatments were then given to 24 birds with or without a synthetic glucocorticoid, dexamethasone (DEX), as a gut dysfunction model. Feed conversion ratio was improved by all the supplemented treatments from day 7 to 35 of age (p < 0.001). DEX injections increased (p < 0.001) the intestinal permeability in all treatments, which tended to be reversed by Arg or MIX. Additional Arg, Arg-Gln, and MIX suppressed (p < 0.05) the overexpression of IL-1β generated by DEX. Feeding birds with MIX treatment increased (p < 0.05) expression of SGLT-1 and glutathione synthetase. In conclusion, tested amino acid supplements were effective in improving feed efficiency and restraining intestinal inflammation caused by DEX through IL-1β pathway.

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Gut integrity and duodenal enteropathogen burden in undernourished children with environmental enteric dysfunction

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009584 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009584

Author(s):

Zehra Jamil ◽

Najeeha Talat Iqbal ◽

Romana Idress ◽

Zubair Ahmed ◽

Kamran Sadiq ◽

...

Keyword(s):

Intestinal Permeability ◽

Linear Growth ◽

Intestinal Inflammation ◽

Nutritional Intervention ◽

Barrier Dysfunction ◽

Growth Faltering ◽

Multivariable Regression Model ◽

Environmental Enteric Dysfunction ◽

Multivariable Regression ◽

Taqman Array

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

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Intra-Individual Variation in Serum AZT Concentration is Not Related to Intestinal Absorption or Small Intestinal Inflammatory Changes in Human Immunodeficiency Virus-Infected Subjects

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029700800405 ◽

1997 ◽

Vol 8 (4) ◽

pp. 327-332 ◽

Cited By ~ 6

Author(s):

RA Sherwood ◽

JT Marsden ◽

CA Stein ◽

S Somasundaram ◽

C Aitken ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Urinary Excretion ◽

Intestinal Permeability ◽

Absorptive Capacity ◽

Individual Variation ◽

Half Life ◽

Intestinal Inflammation ◽

Immunodeficiency Virus ◽

Small Intestinal ◽

Inflammatory Changes

3′-Azido-3′-deoxythymidine (AZT; zidovudine) either alone or in combination with didanosine or another nucleoside analogue is the first-line treatment for patients with human immunodeficiency virus (HIV) infection, many of whom have concurrent gastrointestinal (GI) disease. This study assessed whether the absorption of AZT was affected by GI disease. The absorption and pharmacokinetics of AZT in 23 HIV-infected individuals was measured after a single dose of AZT and was related in 12 patients to small intestinal function. Levels of AZT and its metabolite 5′-glucopyranuronosylthymidine (G-AZT) were measured by radioimmunoassay. Intestinal permeability was assessed by differential urinary excretion of orally administered lactulose/1-rhamnose; absorptive capacity was measured simultaneously by the urinary excretion of 3-o-methyl-D-glucose, d-xylose and 1-rhamnose. Small intestinal inflammation was assessed by faecal excretion of indium-labelled neutrophils. Peak levels of AZT in serum varied between 170 and 1820 ng mL−1. The metabolite G-AZT was present in serum at peak concentrations varying from 1020 to 9930 ng mL−1. There was up to a sevenfold variation in the area under the curve (AUC). The time to maximum serum concentration for AZT was between 30 and 120 min, with an absorption half-life of between 2 and 38 min. The median elimination half-life was 57 min (range 46–72 min), close to the predicted half-life of 60 min. Intestinal permeability was increased in six of the 12 subjects studied and eight had evidence of reduced absorptive capacity. Ten of the 12 patients had evidence of small intestinal inflammation. We concluded that neither changes in permeability nor absorptive capacity influenced the absorption of AZT. There was no relationship between the presence of intestinal inflammation and AZT absorption. This study showed a significant intra-individual variation of serum AZT levels which cannot be explained on the basis of altered intestinal absorptive capacity or intestinal inflammatory changes.

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Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut

Mediators of Inflammation ◽

10.1155/2015/628157 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 181

Author(s):

Andrea Michielan ◽

Renata D’Incà

Keyword(s):

Inflammatory Bowel Disease ◽

Intestinal Permeability ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Mucosal Barrier ◽

Mucosal Inflammation ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Sugar Absorption ◽

Inflammatory Bowel

The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability. These alterations may represent a primary dysfunction in Crohn’s disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course. Functional tests, such as the sugar absorption tests or the novel imaging technique using confocal laser endomicroscopy, allow anin vivoassessment of gut barrier integrity. Antitumor necrosis factor-α(TNF-α) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.

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Microbiota composition and intestinal integrity remain unaltered after the inclusion of hydrolysed Nannochloropsis gaditana in Sparus aurata diet

Scientific Reports ◽

10.1038/s41598-021-98087-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

I. M. Cerezo-Ortega ◽

D. E. Di Zeo-Sánchez ◽

J. García-Márquez ◽

I. Ruiz-Jarabo ◽

M. I. Sáez-Casado ◽

...

Keyword(s):

Intestinal Permeability ◽

Intestinal Microbiota ◽

Unsaturated Fatty Acids ◽

Intestinal Inflammation ◽

Sparus Aurata ◽

Fish Diet ◽

Nannochloropsis Gaditana ◽

Variable Regions ◽

Carnivorous Fish ◽

Mediterranean Countries

AbstractThe use of lysed microalgae in the diet of carnivorous fish can increase the bioavailability of proteins and bioactive compounds, such as unsaturated fatty acids or vitamins in the digestive tract. These are essential molecules for the proper physiological development of fish in aquaculture. However, some antinutritional components and other undesirable molecules can be released from an excess of microalgae supplied, compromising the integrity of the intestine. The inclusion of small amounts of hydrolized microalgae in the fish diet can be a good strategy to avoid negative effects, improving the availability of beneficial compounds. Nannochloropsis gaditana is an interesting microalgae as it contains nutraceuticals. Previous studies reported beneficial effects after its inclusion in the diet of Sparus aurata, a widely cultured species in Europe and in all Mediterranean countries. However, administration of raw microalgae can produce intestinal inflammation, increased intestinal permeability, bacterial translocation and disturbance of digestion and absorption processes. The aim of this study was to evaluate changes in the intestinal microbiota and barrier stability of S. aurata fed with low inclusion (5%) hydrolysed N. gaditana. Intestinal microbiota was analyzed using Illumina MiSeq technology and libraries were constructed using variable regions V3–V4 of 16S rDNA molecules. Analysis were based in the identification, quantification and comparison of sequences. The predictive intestinal microbial functionality was analyzed with PICRUSt software. The results determined that the intestinal microbiota bacterial composition and the predictive intestinal microbiota functionality did not change statistically after the inclusion of N. gaditana on the diet. The study of gene expression showed that genes involved in intestinal permeability and integrity were not altered in fish treated with the experimental diet. The potential functionality and bacterial taxonomic composition of the intestinal microbiota, and the expression of integrity and permeability genes in the intestine of the carnivorous fish S. aurata were not affected by the inclusion of hydrolysed 5% N. gaditana microalgae.

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Roux-En-Y Gastric Bypass Improved Intestinal Permeability by Regulating Gut Innate Immunity in Diet-Induced Obese Mice

10.21203/rs.3.rs-132279/v1 ◽

2020 ◽

Author(s):

Zhangliu Jin ◽

Kai Chen ◽

Zhe Zhou ◽

Weihui Peng ◽

Wei Liu

Keyword(s):

Innate Immunity ◽

Gastric Bypass ◽

Intestinal Permeability ◽

Sham Group ◽

Intestinal Inflammation ◽

Sham Operation ◽

Mrna Levels ◽

Obese Mice ◽

Enhanced Production ◽

The Impact

Abstract Roux-en-Y gastric bypass (RYGB) has been proven to be the most effective treatment for morbid obesity, yet the impact of RYGB on intestinal permeability is fully unknown. In this work, we subjected obese mice to RYGB and sham operation procedures. Serum lipopolysaccharide (LPS), inflammatory cytokines and intestinal permeability were measured at 8 weeks postsurgery. In contrast to sham surgery, RYGB reduced body weight, improved glucose tolerance and insulin resistance, and decreased serum levels of LPS, IL6 and TNFα. Intestinal permeability of the common limb and colon was significantly improved in the RYGB group compared to the sham group. The mRNA levels of IL1β, IL6, and TLR4 of the intestine were significantly decreased in the RYGB group compared with the sham group. The expression of intestinal islet-derived 3β (REG3β), islet-derived 3γ (REG3γ) and IAP was higher in the RYGB group than in the sham group. In conclusion, in a diet-induced obesity (DIO) mouse model,RYGB improved intestinal permeability and attenuated systemic inflammation by downregulating intestinal inflammation and innate immunity, which might result from enhanced production of IAP and antimicrobial peptides.

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MMP-9-induced increase in intestinal epithelial tight permeability is mediated by p38 kinase signaling pathway activation of MLCK gene

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00126.2018 ◽

2019 ◽

Vol 316 (2) ◽

pp. G278-G290 ◽

Cited By ~ 8

Author(s):

Rana Al-Sadi ◽

Moustafa Youssef ◽

Manmeet Rawat ◽

Shuhong Guo ◽

Karol Dokladny ◽

...

Keyword(s):

Protein Expression ◽

Intestinal Permeability ◽

Barrier Function ◽

Intestinal Inflammation ◽

Gene Activity ◽

Intestinal Epithelial ◽

P38 Kinase ◽

Kinase Signaling Pathway

Matrix metalloproteinase-9 (MMP-9) has been implicated as being an important pathogenic factor in inflammatory bowel disease (IBD). MMP-9 is markedly elevated in intestinal tissue of patients with IBD, and IBD patients have a defective intestinal tight-junction (TJ) barrier manifested by an increase in intestinal permeability. The loss of intestinal epithelial barrier function is an important contributing factor in the development and prolongation of intestinal inflammation; however, the role of MMP-9 in intestinal barrier function remains unclear. The purpose of this study was to investigate the effect of MMP-9 on the intestinal epithelial TJ barrier and to delineate the intracellular mechanisms involved by using in vitro (filter-grown Caco-2 monolayers) and in vivo (mouse small intestine recycling perfusion) systems. MMP-9 caused a time- and dose-dependent increase in Caco-2 TJ permeability. MMP-9 also caused an increase in myosin light-chain kinase (MLCK) gene activity, protein expression, and enzymatic activity. The pharmacological MLCK inhibition and siRNA-induced knockdown of MLCK inhibited the MMP-9-induced increase in Caco-2 TJ permeability. MMP-9 caused a rapid activation of the p38 kinase signaling pathway and inhibition of p38 kinase activity prevented the MMP-9-induced increase in MLCK gene activity and the increase in Caco-2 TJ permeability. MMP-9 also caused an increase in mouse intestinal permeability in vivo, which was accompanied by an increase in MLCK expression. The MMP-9-induced increase in mouse intestinal permeability was inhibited in MLCK-deficient mice. These data show for the first time that the MMP-9-induced increase in intestinal TJ permeability in vitro and in vivo was mediated by the p38 kinase signal transduction pathway upregulation of MLCK gene activity and that therapeutic targeting of these pathways can prevent the MMP-9-induced increase in intestinal TJ permeability. NEW & NOTEWORTHY MMP-9 is highly elevated in patients with IBD. IBD patients have compromised intestinal TJ barrier function manifested by an increase in intestinal permeability and intestinal inflammation. This study shows that MMP-9, at clinically achievable concentrations, causes an increase in intestinal TJ permeability in vitro and in vivo. In addition, a MMP-9-induced increase in intestinal TJ permeability was mediated by an increase in MLCK gene and protein expression via the p38 kinase pathway.

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Intestinal permeability and inflammation in patients on NSAIDs

Gut ◽

10.1136/gut.43.4.506 ◽

1998 ◽

Vol 43 (4) ◽

pp. 506-511 ◽

Cited By ~ 111

Author(s):

G Sigthorsson ◽

J Tibble ◽

J Hayllar ◽

I Menzies ◽

A Macpherson ◽

...

Keyword(s):

Intestinal Permeability ◽

Intestinal Inflammation ◽

Test Dose ◽

Faecal Excretion ◽

Intestinal Integrity ◽

Number Of Patients ◽

Significant Difference ◽

Indium 111 ◽

Small Intestinal ◽

Inflammatory Changes

Background—The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain.Aims—To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs.Methods—Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar). Two hundred and eighty six patients on 12 different NSAIDs underwent indium-111 white cell faecal excretion studies to assess the prevalence and severity of intestinal inflammation.Results—The iso- and hyperosmolar tests showed significant malabsorption of 3–0-methyl-d-glucose, d-xylose, andl-rhamnose. Intestinal permeability changes were significantly more pronounced and frequent with the hypo- and hyperosmolar as opposed to the iso-osmolar test. Sequential studies showed that four and nine patients (of 13) developed inflammation after three and six months treatment with NSAIDs, respectively. There was no significant difference (p>0.1) in the prevalence (54–72%) or severity of intestinal inflammation in the 286 patients taking the various NSAIDs apart from those on aspirin and nabumetone, these having no evidence of intestinal inflammation. There was no significant correlation between the inflammatory changes and age, sex, dose of NSAID, length of disease, or NSAID ingestion.Conclusions—Intestinal permeability test dose composition is an important factor when assessing the effects of NSAIDs on intestinal integrity. All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.

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