scholarly journals Effects of intestinal alkaline phosphatase on intestinal barrier function in a cecal ligation and puncture (CLP)‐induced mouse model for sepsis

2019 ◽  
Vol 32 (3) ◽  
Author(s):  
Philip Plaeke ◽  
Joris G. De Man ◽  
Annemieke Smet ◽  
Surbhi Malhotra‐Kumar ◽  
Isabel Pintelon ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Mouse Model ◽  
Barrier Function ◽  
Cecal Ligation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Cecal Ligation And Puncture ◽  
Intestinal Alkaline Phosphatase

scholarly journals Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Siddhartha S Ghosh ◽  
Jing Wang ◽  
Paul J Yannie ◽  
Shobha Ghosh
Keyword(s):  
Barrier Function ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Disease Development ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Targeted Interventions ◽  
Associated Diseases

Abstract The intestinal barrier is complex and consists of multiple layers, and it provides a physical and functional barrier to the transport of luminal contents to systemic circulation. While the epithelial cell layer and the outer/inner mucin layer constitute the physical barrier and are often referred to as the intestinal barrier, intestinal alkaline phosphatase (IAP) produced by epithelial cells and antibacterial proteins secreted by Panneth cells represent the functional barrier. While antibacterial proteins play an important role in the host defense against gut microbes, IAP detoxifies bacterial endotoxin lipopolysaccharide (LPS) by catalyzing the dephosphorylation of the active/toxic Lipid A moiety, preventing local inflammation as well as the translocation of active LPS into systemic circulation. The causal relationship between circulating LPS levels and the development of multiple diseases underscores the importance of detailed examination of changes in the “layers” of the intestinal barrier associated with disease development and how this dysfunction can be attenuated by targeted interventions. To develop targeted therapies for improving intestinal barrier function, it is imperative to have a deeper understanding of the intestinal barrier itself, the mechanisms underlying the development of diseases due to barrier dysfunction (eg, high circulating LPS levels), the assessment of intestinal barrier function under diseased conditions, and of how individual layers of the intestinal barrier can be beneficially modulated to potentially attenuate the development of associated diseases. This review summarizes the current knowledge of the composition of the intestinal barrier and its assessment and modulation for the development of potential therapies for barrier dysfunction-associated diseases.

scholarly journals Impaired intestinal barrier function in a mouse model of hyperuricemia

2019 ◽  
Author(s):  
Yingjie Guo ◽  
Hailong Li ◽  
Zhen Liu ◽  
Changgui Li ◽  
Yunqing Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function

scholarly journals Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Min-Jung Bae ◽  
Hee Soon Shin ◽  
Hye-Jeong See ◽  
Sun Young Jung ◽  
Da-Ae Kwon ◽  
...  
Keyword(s):  
T Cells ◽  
Food Allergy ◽  
Mouse Model ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function

scholarly journals Consumption of non-digestible oligosaccharides elevates colonic alkaline phosphatase activity by up-regulating the expression ofIAP-I, with increased mucins and microbial fermentation in rats fed a high-fat diet

2018 ◽  
Vol 121 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Yukako Okazaki ◽  
Tetsuyuki Katayama
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Organic Acids ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Microbial Fermentation ◽  
Sprague Dawley ◽  
Intestinal Alkaline Phosphatase ◽  
Alp Activity ◽  
Fermentable Carbohydrates

AbstractWe have recently reported that soluble dietary fibre, glucomannan, increased colonic alkaline phosphatase (ALP) activity and the gene expression without affecting the small-intestinal activity and that colonic ALP was correlated with gut mucins (index of intestinal barrier function). We speculated that dietary fermentable carbohydrates including oligosaccharides commonly elevate colonic ALP and gene expression as well as increase mucin secretion and microbial fermentation. To test this hypothesis, male Sprague–Dawley rats were fed a diet containing 30 % lard with or without 4 % fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), raffinose (RAF) and lactulose (LAC), which are non-digestible oligosaccharides or isomalto-oligosaccharides (IMOS; some digestible oligosaccharides) for 2 weeks. Colon ALP activity, the gene expression and gut luminal variables including mucins, organic acids and microbiota were measured. Colonic ALP was significantly elevated in the FOS, RAF and LAC groups, and a similar trend was observed in the GOS group. Colonic expression of intestinal alkaline phosphatase (IAP-I), an ALP gene, was significantly elevated in the FOS, GOS and RAF groups and tended to be increased in the LAC group. Dietary FOS, GOS, RAF and LAC significantly elevated faecal mucins, caecaln-butyrate and faecal ratio ofBifidobacteriumspp. Dietary IMOS had no effect on colonic ALP, mucins, organic acids and microbiota. Colon ALP was correlated with mucins, caecaln-butyrate and faecalBifidobacteriumspp. This study demonstrated that non-digestible and fermentable oligosaccharides commonly elevate colonic ALP activity and the expression ofIAP-I, with increasing mucins and microbial fermentation, which might be important for protection of gut epithelial homoeostasis.

scholarly journals Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis

2021 ◽  
Author(s):  
Siddhartha S Ghosh ◽  
Jing Wang ◽  
Paul J Yannie ◽  
Remy C Cooper ◽  
Yashnoor K Sandhu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Lipid Absorption ◽  
Apical Surface ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Over Expression ◽  
Intestinal Barrier Dysfunction

Rationale: Intestinal Alkaline Phosphatase (IAP) is secreted by enterocytes and is present on the apical surface. It not only detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen and limits intestinal inflammation but also restricts translocation of LPS into systemic circulation. Diet-induced intestinal barrier dysfunction and subsequent development of metabolic endotoxemia seen in diabetes and heart disease is associated with reduced IAP levels. To examine the direct effects of increased IAP expression on barrier function and development of metabolic diseases, we developed intestine-specific IAP transgenic mice (IAP Tg ) over-expressing human chimeric IAP. Objective: The aim of this study was to evaluate the effects of intestine-specific IAP overexpression on Western-type diet (WD)-induced atherosclerosis in Ldlr -/- mice. Methods and Results: IAPTg mice crossed into Ldlr -/- background (Ldlr-/-IAP Tg ) and Ldlr -/- littermates were fed WD for 16 weeks. Intestinal barrier dysfunction was assessed by monitoring plasma LPS levels and histological examination of colon. Over-expression of IAP attenuated WD-induced disruption of the colonic mucous layer, reducing intestinal barrier dysfunction and plasma LPS levels. Significant reduction in body, liver and adipose tissue weight was also seen in WD-fed Ldlr -/- IAP Tg mice. Plasma and hepatic lipids were also significantly reduced in WD-fed Ldlr -/- IAP Tg mice. Consistently, intestinal lipid absorption was attenuated in Ldlr -/- IAP Tg mice with reduced expression of apical lipid transporters (CD36, FATP4 and NPC1L1) and intracellular lipid transport proteins (FABP1/2, SCP2). Attenuation of WD-induced atherosclerosis in Ldlr -/- IAP Tg mice was demonstrated by significant reduction in arch and total aortic lesions as seen by enface analyses as well as significantly reduced atherosclerotic lesions in the ascending aorta of these mice. Conclusions: IAP overexpression improves intestinal barrier function by maintaining the integrity of the mucin layer in WD fed Ldlr -/- IAPTg mice and attenuates intestinal lipid absorption. Thus, by limiting translocation of gut-derived LPS and/or reducing plasma lipids, over-expression of IAP attenuates development of WD-induced atherosclerosis.

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