Systemic inflammation in absence of gut bacterial translocation in C57BL/6 mice with cirrhosis

Úbeda, María; Lario, M.; Muñoz, L.; Díaz, David; Borrero, M.J.; García‐Bermejo, Laura; Álvarez‐Mon, Melchor; Albillos, Agustı́n

doi:10.1136/gutjnl-2012-302920

Cited by 4 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence suggests that translocation of bacterial and bacterial products plays a causal role in the pathogenesis of chronic liver diseases and their complications [28]. In agreement with previous studies [6], [29], our findings showed significant morphological alterations in intestinal epithelial barrier in CCl 4 -induced liver cirrhotic rats. The results indicate that disruption of intestinal epithelial barrier is involved in the pathogenesis of liver cirrhosis in rats and oxymatrine can restore the integrity of intestinal epithelial barrier.…”

Section: Discussionsupporting

confidence: 92%

“…Inflammation response is a crucial part of the defense mechanisms against bacteria and bacterial product-induced tissue damages [5], [6], and it has been implicated in the initiation, development, and progression of intestinal barrier dysfunction, BT, and eventually cirrhosis. Nuclear factor κB (NF-κB) family comprises of RelA, c-Rel, RelB, and NF-κB1(p105/p50) and they are critical transcription factors involved in various cellular responses to stimuli such as cytokines and bacterial/viral antigens [7]–[9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

et al. 2014

View full text Add to dashboard Cite

Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…We have proposed that inflammation precedes BT, despite the fact that they feedback each other, in cirrhosis . In fact, systemic inflammation has been described in the absence of BT in experimental cirrhosis, and the reduction of inflammatory environment and improvement of gut barrier integrity markers by means of the Farnesoid X receptor agonist obeticholic acid has been associated with a significant reduction of BT in cirrhotic rats . Our results, in line with this evidence, would point to a progressive depletion of the intestinal Treg population that controls local proinflammatory differentiation as a possible mechanism to explain increased BT observed in advanced cirrhosis.…”

Section: Discussionsupporting

confidence: 81%

Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short‐Chain Fatty Acids in Experimental Cirrhosis

et al. 2018

View full text Add to dashboard Cite

Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota–derived short‐chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild‐type and recombination activating gene 1 (Rag1)‐/‐ mice. Naive T cells and Treg cells were transferred into Rag1 ‐/‐ mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight‐junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography–mass spectrometry in colonic content before and after E. coli challenge. Rag1 ‐/‐ mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in Rag1 ‐/‐ mice. Naive T and Treg replenishment in Rag1 ‐/‐ mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1 ‐/‐ mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1 ‐/‐ mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria‐derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.

show abstract

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats

Úbeda

Lario

Muñoz

et al. 2016

Journal of Hepatology

147

136

View full text Add to dashboard Cite

Systemic inflammation in absence of gut bacterial translocation in C57BL/6 mice with cirrhosis

Cited by 4 publications

References 11 publications

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short‐Chain Fatty Acids in Experimental Cirrhosis

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats

Contact Info

Product

Resources

About