Chenodeoxycholic Acid (CDCA) Protects against the Lipopolysaccharide-Induced Impairment of the Intestinal Epithelial Barrier Function via the FXR-MLCK Pathway

Song, Min; Ye, Jiayi; Zhang, Fenglin; Han, Seung-Beom; Yang, Xiaohua; He, Haiwen; Liu, Fangfang; Zhu, Xiaotong; Wang, Lina; Gao, Ping; Shu, Gang; Jiang, Qingyan; Wang, Songbo

doi:10.1021/acs.jafc.9b03173

Cited by 59 publications

(40 citation statements)

References 46 publications

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“…At present, reports about the direct relationship between CDCA and EMS are not available, but many studies show that CDCA is closely related to gut microbiota and contributes to promoting intestinal homeostasis. CDCA blocks lipopolysaccharide (LPS)‐induced activation of the myosin light chain kinase (MLCK) pathway in an FXR‐dependent manner, thereby protecting the intestinal epithelial barrier function 27,28 . Animal studies have shown that UDCA can stimulate the migration of intestinal epithelial cells and protect the intestinal barrier through EGFR and COX‐2‐dependent mechanisms, 29 thus alleviating the inflammatory response and reducing the levels of TNF‐α, IL‐1β, and IL‐6 30 .…”

Section: Discussionmentioning

confidence: 99%

Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

Sun

et al. 2020

American J Rep Immunol

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Problem: Endometriosis (EMS) is a chronic inflammatory disease with unclear pathogenesis. Three studies have uncovered the influence of gut microbiota on mice with EMS, but no study has investigated the characteristics of fecal metabolomics to determine some important clues on EMS. This research aims to uncover the interaction between fecal metabolomics and gut microbiota in EMS mice. Method of study: Female C57BL/6J mice were used to construct the EMS model. Non-target metabolomics was applied to detect the fecal metabolites of EMS mice. The 16s rRNA sequencing was used for clarifying the composition of the gut microbiota. The functional characteristics of gut microbiota were analyzed using the PICRUSt. The receiver operator characteristic curve (ROC) analysis was utilized for determining the potential important differential metabolites, and the Spearman correlation coefficient was applied for expressing the correlation between the important differential metabolites and gut microbiota. Results: A total of 156 named differential metabolites were screened. The diversity and the abundance of gut microbiota in EMS mice decreased. Eleven pathways were involved in the differential metabolites and the functional prediction of gut microbiota, among which the second bile acid biosynthesis and alpha-linolenic acid (ALA) metabolism were the significant enrichment pathways. The increased abundance of chenodeoxycholic and ursodeoxycholic acids and the decreased abundance of ALA and 12,13-EOTrE were found in the feces of EMS mice. Conclusion: The abnormal fecal metabolites, which are influenced by dysbacteriosis, may be the characteristics of EMS mice and can be the potential important indices to distinguish the disease.

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Section: Discussionmentioning

confidence: 99%

Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

Sun

et al. 2020

American J Rep Immunol

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“…Cholestasis has been reported to decrease membrane resistance in the small intestine, decrease claudin‐1 and occludin expression, enhance mucosal permeability, and improve permeability by the administration of an agonist of farnesoid X receptor (FXR), which is a nuclear receptor for bile acids (Verbeke et al, ). Exposure of the apical membrane of epithelial cells to bile acids has been reported to restore the reduced expression of claudin‐1, ZO‐1, and occludin via the FXR‐MLCK pathway (Song et al, ). Therefore, reduced FXR activation was suggested to be involved in the down‐regulation of tight junction proteins and the increase of permeability.…”

Section: Discussionmentioning

confidence: 99%

Increased membrane permeation and blood concentration of 6‐carboxyfluorescein associated with dysfunction of paracellular route barrier in the small intestine of ulcerative colitis model rats

Kumagai

Ishii

Morimoto

et al. 2020

Biopharm & Drug Disp

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In the colon of patients with ulcerative colitis (UC), decreased function of the paracellular barrier, especially hypofunction of the tight junction, is associated with pathological conditions. However, there has been no report to date on the function of tight junctions in the small intestine. Here, we focused on the barrier function of the small intestine, especially in tight junctions, and compared it with that of the colon. Dextran sulfate sodium (DSS) was used to induce ulcerative colitis in rats in order to evaluate the function of the paracellular barrier in the jejunum, ileum, and colon. An in vitro diffusion chamber method was used to evaluate membrane resistance, which is an index of tight junction function and mucosal permeability, using 6-carboxyfluorescein (6-CF), a paracellular marker. In the jejunum and colon, with decrease of membrane resistance in the DSS group, mucosal permeability increased, whereas no marked difference was observed in the ileum. In the in situ closed-loop method, absorption of 6-CF from the jejunum was higher than that from the ileum.Immunohistochemical staining of claudin-4 showed heterogeneous attenuation of claudin-4 in the jejunum. Pharmacokinetic parameters were calculated from the blood concentration after intravenous injection and oral administration of 6-CF. In the DSS group, there was a delay in the elimination phase, suggesting a decrease in renal function, and an increase in maximum blood concentration, associated with an increased absorption rate constant. The increased absorption and decreased renal function due to decreased paracellular barrier function in the small intestine and colon may cause fluctuations in drug efficacy and side effects. K E Y W O R D S membrane resistance, paracellular route, small intestine, tight junction, ulcerative colitis

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“…In terms of metabolites, alpha-linoleic acid (ALA), chenodeoxycholic (CDCA), ursodeoxycholic acid (UDCA) and 12,11, contributed most to differences in fecal metabolome. Ni et al (2020) suggest that CDCA, UDCA, and ALA have a protective role in the intestinal wall because of their anti-inflammatory effects (Paula et al 2018, Ko et al 2019, Song et al 2019, while 12,13-EOTrE may be related to inflammation and serve as a potential biomarker of endometriosis. Despite such findings, further studies are necessary to understand the correlation between endometriosis and these compounds (Ni et al 2020).…”

Section: Metabolomics and Endometriosismentioning

confidence: 99%

Metabolomics in endometriosis: challenges and perspectives for future studies

Ortiz

Torres-Reverón

Appleyard

2021

Reproduction and Fertility

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Endometriosis is a complex disease characterized by inflammation and the growth of endometrial- like glands and stroma outside the uterine cavity. The pathophysiology of endometriosis is not entirely understood, however, with a prevalence of ~10% of women in their reproductive years the disease symptoms significantly affect the quality of life of millions of women globally. Metabolomic studies have previously identified specific metabolites that could be a signature of endometriosis. This approach could potentially be used as a non-invasive tool for early diagnosis and provide a better understanding of endometriosis pathophysiology. This review aims to provide insight as to how endometriosis affects the metabolome by reviewing different studies that have used this approach to design follow up studies. The search query included the term “endometriosis” in combination with “metabolomics,” “lipidomics,” or “sphingolipidomics,” published between 2012 and 2020. We included studies in humans and animal models. Most studies reported for differences in the metabolome of subjects with endometriosis in comparison to healthy controls and used samples taken from serum, endometrial tissue, follicular fluid, urine, peritoneal fluid, or endometrial fluid. Statistically significant metabolites contributed to group separation between patients and healthy controls. Reported metabolites included amino acids, lipids, organic acids, and other organic compounds. Differences in methods, analytical techniques, and the presence of confounding factors can interfere with results and interpretation of data. Metabolomics seems to be a promising tool for identifying significant metabolites in patients with endometriosis. Nonetheless, more investigation is needed in order to understand the significance of the study results.

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Chenodeoxycholic Acid (CDCA) Protects against the Lipopolysaccharide-Induced Impairment of the Intestinal Epithelial Barrier Function via the FXR-MLCK Pathway

Cited by 59 publications

References 46 publications

Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

Increased membrane permeation and blood concentration of 6‐carboxyfluorescein associated with dysfunction of paracellular route barrier in the small intestine of ulcerative colitis model rats

Metabolomics in endometriosis: challenges and perspectives for future studies

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