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

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.

scholarly journals Roux-en-Y gastric bypass potentially improved intestinal permeability by regulating gut innate immunity in diet-induced obese mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhangliu Jin ◽  
Kai Chen ◽  
Zhe Zhou ◽  
Weihui Peng ◽  
Wei Liu
Keyword(s):  
Innate Immunity ◽  
Gastric Bypass ◽  
Intestinal Permeability ◽  
Sham Group ◽  
Sham Operation ◽  
Mrna Levels ◽  
Obese Mice ◽  
Post Surgery ◽  
Enhanced Production ◽  
The Impact

AbstractRoux-en-Y gastric bypass (RYGB) has been demonstrated to be the most effective treatment for morbid obesity, yet the impact of RYGB on intestinal permeability is not fully known. In this work, we subjected obese mice to RYGB and sham operation procedures. Serum lipopolysaccharide (LPS) level, inflammatory cytokines and intestinal permeability were measured at 8 weeks post surgery. 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 in the intestine were significantly decreased in the RYGB group compared with the sham group. The expression levels of intestinal islet-derived 3β (REG3β), islet-derived 3γ (REG3γ) and intestinal alkaline phosphatase (IAP) were higher in the RYGB group than in the sham group. In conclusion, in a diet-induced obesity (DIO) mouse model, both decreased intestinal permeability and attenuated systemic inflammation after RYGB surgery were associated with improved innate immunity, which might result from enhanced production of IAP and antimicrobial peptides.

HETEs enhance IL-1-mediated COX-2 expression via augmentation of message stability in human colonic myofibroblasts

2007 ◽  
Vol 293 (4) ◽  
pp. G719-G728 ◽  
Author(s):  
J. F. Di Mari ◽  
J. I. Saada ◽  
R. C. Mifflin ◽  
J. D. Valentich ◽  
D. W. Powell
Keyword(s):  
Rna Binding ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Protein Activation ◽  
Colonic Adenomas ◽  
Cox 2 ◽  
Message Stabilization ◽  
The Impact

Proinflammatory cytokines and eicosanoids are central players in intestinal inflammation. IL-1, a key cytokine associated with intestinal mucosal inflammation, induces COX-2 expression in human colonic myofibroblasts (CMF) and increased prostaglandin E2secretion is associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). We have previously demonstrated that IL-1α-induced cyclooxygenase-2 (COX-2) expression is the result of NF-κB- and ERK-mediated transcription, as well as COX-2 message stabilization, which depends on p38, MAPKAPK-2 (MK-2) and human antigen R (HuR) RNA binding protein activation. Lipoxygenase (LOX)-derived hydroxyeicosatetraenoic acids (HETEs) are elevated in IBD and colonic adenomas and “cross talk” has been observed between the COX and LOX pathways. Since COX-2 expression is primarily in CMFs in colonic adenomas, we examined the impact of LOX metabolites, particularly HETEs, on IL-1α-induced COX-2 expression in human CMFs. Although 5(S)-, 12(R)-, and 15(S)-HETEs alone had little to no effect on COX-2 expression, they enhanced IL-1-mediated COX-2 expression 3.6 ± 0.5-fold. Studies utilizing heterogeneous nuclear RNA amplification and 5,6-dichloro-β-d-ribofuranosylbenzimidazole treatment were undertaken to measure COX-2 transcription and message stabilization, respectively. We found that HETEs enhanced IL-1-induced COX-2 mRNA levels in CMF as the result of increased p38, MK-2, and HuR activity, increasing message stability greater than that observed with IL-1 alone. Thus HETEs can act synergistically with IL-1α to induce COX-2 expression in human CMFs. HETEs may play a role in both colonic inflammation and in increasing the risk of CRC in IBD independently and via induction of COX-2-mediated prostaglandin secretion.

scholarly journals Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 384 ◽  
Author(s):  
Sonia Shastri ◽  
Tanvi Shinde ◽  
Agampodi Promoda Perera ◽  
Nuri Gueven ◽  
Rajaraman Eri
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Goblet Cells ◽  
Inflammatory Activity ◽  
Mrna Levels ◽  
Anti Inflammatory ◽  
The Impact ◽  
Chronic Intestinal Inflammation

Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in Winnie mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin MUC2 gene. Idebenone (200 mg/kg) was orally administered daily to 5–6 weeks old Winnie mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased MUC2 mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and X-box binding protein-1 (XBP-1) at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring

2008 ◽  
Vol 294 (1) ◽  
pp. G148-G154 ◽  
Author(s):  
Frida Fåk ◽  
Siv Ahrné ◽  
Göran Molin ◽  
Bengt Jeppsson ◽  
Björn Weström
Keyword(s):  
Intestinal Permeability ◽  
Intestinal Inflammation ◽  
Bacterial Colonization ◽  
Digestive Enzyme ◽  
Plasma Concentrations ◽  
Gut Development ◽  
E Coli ◽  
Increased Risk ◽  
And Function ◽  
The Impact

The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e., antibiotic treatment or Escherichia coli exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics 3 days before parturition or live nonpathogenic E. coli Culture Collection of University of Göteborg, Sweden type strain (CCUG 29300T) 1 wk before parturition and up to 14 days of lactation in the drinking water. Cecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels, and intestinal inflammation were studied in 2-wk-old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae, which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability, and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300T, also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth compared with the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen, and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of cecal Enterobacteriaceae, appears to have lasting effects on the postnatal microflora, which affects gut growth and function.

scholarly journals Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3589
Author(s):  
Yasser Morsy ◽  
Nathalie Brillant ◽  
Yannick Franc ◽  
Michael Scharl ◽  
Marcin Wawrzyniak ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gene Locus ◽  
Intestinal Inflammation ◽  
Severe Disease ◽  
Mrna Levels ◽  
Disease Course ◽  
Risk Gene ◽  
Inflammatory Bowel ◽  
The Impact

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.

Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis

2007 ◽  
Vol 292 (2) ◽  
pp. G518-G525 ◽  
Author(s):  
Paola Brun ◽  
Ignazio Castagliuolo ◽  
Vincenza Di Leo ◽  
Andrea Buda ◽  
Massimo Pinzani ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Intestinal Mucosa ◽  
Nonalcoholic Steatohepatitis ◽  
Ussing Chamber ◽  
Portal Blood ◽  
Mucosal Barrier ◽  
Mrna Levels ◽  
Obese Mice ◽  
Bacterial Endotoxins ◽  
Mucosal Barrier Function

A small percentage of pathologically obese subjects with fatty livers develop histological signs of necroinflammation and fibrosis, suggesting a variety of cofactors in the pathogenesis of obesity-related liver diseases including nonalcoholic steatohepatitis. Since several observations have linked bacterial endotoxins to liver damage, the aim of this study was to determine the effect of obesity on intestinal mucosal integrity and portal blood endotoxemia in two strains of obese mice: leptin-deficient ( ob/ ob) and hyperleptinemic ( db/ db) mice. Murine intestinal mucosal barrier function was assessed using a Ussing chamber, whereas ileum tight junction proteins were analyzed by immunocytochemistry and Western blot analysis. Circulating proinflammatory cytokines and portal blood endotoxin levels were measured by ELISA and the limulus test, respectively. The inflammatory and fibrogenic phenotype of murine hepatic stellate cells (HSCs) was determined by ELISA and quantitative RT-PCR. Ob/ ob and db/ db mice showed lower intestinal resistance, profoundly modified distribution of occludin and zonula occludens-1 in the intestinal mucosa, and higher circulating levels of inflammatory cytokines and portal endotoxemia compared with lean control mice. Moreover, HSCs isolated from ob/ ob and db/ db mice showed higher membrane CD14 mRNA levels and more pronounced lipopolysaccharide-induced proinflammatory and fibrogenic responses than HSCs from lean animals. In conclusion, genetically obese mice display enhanced intestinal permeability leading to increased portal endotoxemia that makes HSCs more sensitive to bacterial endotoxins. We suggest that in metabolic syndrome, patients may likewise have a greater intestinal mucosa permeability and increased lipopolysaccharide levels in portal blood that can contribute to the liver inflammatory damage.

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

scholarly journals AB0073 INTESTINAL PERMEABILITY IN SPONDYLOARTHRITIS: A SYSTEMATIC REVIEW OF THE LITERATURE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1067.1-1067
Author(s):  
S. Hecquet ◽  
P. Totoson ◽  
H. Martin ◽  
C. Prati ◽  
D. Wendling ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Activity ◽  
Intestinal Permeability ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Basic Research ◽  
Final Analysis ◽  
Potential Marker ◽  
Inflammatory Drugs ◽  
Permeability Evaluation

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

scholarly journals Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Titanium Dioxide ◽  
Genetic Risk ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Food Additive ◽  
Wild Type ◽  
Dextran Sodium Sulphate ◽  
Risk Gene ◽  
The Impact

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk

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