scholarly journals Connecting metabolism to intestinal barrier function: The role of leptin

2014 ◽  
Vol 2 (4) ◽  
pp. e970940 ◽  
Author(s):  
Gwenola Le Dréan ◽  
Jean-Pierre Segain
Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.


Colitis ◽  
10.5772/25753 ◽  
2012 ◽  
Author(s):  
R.C. Anderson ◽  
J.E. Dalziel ◽  
P.K. Gopal ◽  
S. Bassett ◽  
A. Ellis ◽  
...  

2007 ◽  
Vol 133 (6) ◽  
pp. 2065-2067
Author(s):  
Anupama Ravi ◽  
Didier Merlin ◽  
Shanthi V. Sitaraman

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Anoop Kumar ◽  
Shubha Priyamvada ◽  
Dulari Jayawardena ◽  
Arivarasu N. Anbazhagan ◽  
Ishita Chatterjee ◽  
...  

2020 ◽  
Author(s):  
You-Dong Wan ◽  
Rui-Xue Zhu ◽  
Xin-Ting Pan

ABSTRACTDisorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. Similar results were found in microbiota-depleted AP without BA treatment. However, we did not observe further downregulation of the FXR signaling pathway in microbiota-depleted AP mice given TUDCA, indicating that improvement of pancreatitis by TUDCA may be associated with gut microbiota. Our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors. Taken together, our study shows that supplementation with BAs could improve bile acid-FXR-FGF15 signaling, and reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.


2019 ◽  
Vol 2 (52) ◽  
pp. 10-15
Author(s):  
Togzhan Algazina ◽  
Bakytgul Yermekbayeva ◽  
Almagul Kushugulova ◽  
Samat Kozhakhmetov ◽  
Zulfiya Jetpisbayeva ◽  
...  

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Xiao Sun ◽  
Yalei Cui ◽  
Yingying Su ◽  
Zimin Gao ◽  
Xinying Diao ◽  
...  

ABSTRACT Weaning of piglets is accompanied by intestinal inflammation, impaired intestinal barrier function, and intestinal microflora disorder. Regulating intestinal microflora structure can directly or indirectly affect intestinal health and host growth and development. However, whether dietary fiber (DF) affects the inflammatory response and barrier function by affecting the intestinal microflora and its metabolites is unclear. In this study, we investigated the role of intestinal microflora in relieving immune stress and maintaining homeostasis using piglets with lipopolysaccharide (LPS)-induced intestinal injury as a model. DF improved intestinal morphology and barrier function, inhibited the expression of inflammatory signal pathways (Toll-like receptor 2 [TLR2], TLR4, and NF-κB) and proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor alpha [TNF-α]), and upregulated the expression of barrier-related genes (encoding claudin-1, occludin, and ZO-1). The contents of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and the activity of diamine oxidase in plasma were decreased. Meanwhile, DF had a strong effect on the composition and function of intestinal microflora at different taxonomic levels, the relative abundances of cellulolytic bacteria and anti-inflammatory bacteria were increased, and the concentrations of propionate, butyrate, and total short-chain fatty acids (SCFAs) in intestinal contents were increased. In addition, the correlation analysis also revealed the potential relationship between metabolites and certain intestinal microflora, as well as the relationship between metabolites and intestinal morphology, intestinal gene expression, and plasma cytokine levels. These results indicate that DF improves intestinal barrier function, in part, by altering intestinal microbiota composition and increasing the synthesis of SCFAs, which subsequently alleviate local and systemic inflammation. IMPORTANCE Adding DF to the diet of LPS-challenged piglets alleviated intestinal and systemic inflammation, improved intestinal barrier function, and ultimately alleviated the growth retardation of piglets. In addition, the addition of DF significantly increased the relative abundance of SCFA-producing bacteria and the production of SCFAs. We believe that the improvement of growth performance of piglets with LPS-induced injury can be attributed to the beneficial effects of DF on intestinal microflora and SCFAs, which reduced the inflammatory response in piglets, improving intestinal barrier function and enhancing body health. These research results provide a theoretical basis and guidance for the use of specific fiber sources in the diet to improve intestinal health and growth performance of piglets and thus alleviate weaning stress. Our data also provide insights for studying the role of DF in regulating gastrointestinal function in human infants.


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