Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions

Slifer, Zachary; Hernández, L. A.; Pridgen, Tiffany; Carlson, Alexandra R; Messenger, Kristen M.; Madan, Jay; Krishnan, B Radha; Laumas, Sandeep; Blikslager, Anthony T.

doi:10.1371/journal.pone.0250165

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…For instance, Larazotide acetate is a small, TJ-directed drug that is currently in clinical trials for treatment of celiac disease, the pathophysiology of which includes disruptions to the intestinal TJs [130][131][132][133]. Several in vivo and in vitro experiments have demonstrated that Larazotide administration prevents relocalization of crucial TJ-proteins, ultimately resulting in quantifiably enhanced epithelial barrier integrity [134][135][136]. Taken together, these studies introduce the exciting prospect of compounding pre-and probiotic's beneficial effects with Larazotide or similar TJ-protein-directed pharmaceuticals.…”

Section: Future Directions: Embracing the Enteric Glial Cell Network Large Animal Models And Promising Clinical Interventionsmentioning

confidence: 99%

Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function

Rose

Odle

Blikslager

et al. 2021

IJMS

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Disruptions in the intestinal epithelial barrier can result in devastating consequences and a multitude of disease syndromes, particularly among preterm neonates. The association between barrier dysfunction and intestinal dysbiosis suggests that the intestinal barrier function is interactive with specific gut commensals and pathogenic microbes. In vitro and in vivo studies demonstrate that probiotic supplementation promotes significant upregulation and relocalization of interepithelial tight junction proteins, which form the microscopic scaffolds of the intestinal barrier. Probiotics facilitate some of these effects through the ligand-mediated stimulation of several toll-like receptors that are expressed by the intestinal epithelium. In particular, bacterial-mediated stimulation of toll-like receptor-2 modulates the expression and localization of specific protein constituents of intestinal tight junctions. Given that ingested prebiotics are robust modulators of the intestinal microbiota, prebiotic supplementation has been similarly investigated as a potential, indirect mechanism of barrier preservation. Emerging evidence suggests that prebiotics may additionally exert a direct effect on intestinal barrier function through mechanisms independent of the gut microbiota. In this review, we summarize current views on the effects of pro- and prebiotics on the intestinal epithelial barrier as well as on non-epithelial cell barrier constituents, such as the enteric glial cell network. Through continued investigation of these bioactive compounds, we can maximize their therapeutic potential for preventing and treating gastrointestinal diseases associated with impaired intestinal barrier function and dysbiosis.

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Section: Future Directions: Embracing the Enteric Glial Cell Network Large Animal Models And Promising Clinical Interventionsmentioning

confidence: 99%

Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function

Rose

Odle

Blikslager

et al. 2021

IJMS

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“…It had been reported that 1 μM of AT1001 can blocked the ischemia-induced TJ dysfunction but higher concentration (10 μM) of AT1001 did not elicit better protective effects 32 , 33 . So, in preliminary experiments (n = 3 in each group), the dose-dependent effects of 5 μM, 10 μM, 20 μM of AT1001 for the inhibition of LPS-induced zonulin release in supernatant of Coca2 cells were tested.…”

Section: Methodsmentioning

confidence: 90%

Prediction models combining zonulin, LPS, and LBP predict acute kidney injury and hepatorenal syndrome–acute kidney injury in cirrhotic patients

Lin

Kuo

Shen

et al. 2023

Sci Rep

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The development of acute kidney injury (AKI) and hepatorenal syndrome–acute kidney injury (HRS–AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS–AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS–AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS–AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child–Pugh score for HRS–AKI. The area under curve (AUC) for the prediction of AKI and HRS–AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS–AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients.

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“…Larazotide prevents TJ opening, being able to block zonulin receptors locally, by joining the receptors itself, decreasing TJ detachment and promoting TJ assembly and structural filaments rearrangement (288). Larazotide was developed for the treatment of CD (289) and later tested in type 1 diabetes, inflammatory bowel disease, Kawasaki disease, respiratory diseases (290), collagen-induced arthritis (291) and intestinal ischemic injury (292,293).…”

Section: Larazotidementioning

confidence: 99%

Present and Future Therapeutic Approaches to Barrier Dysfunction

et al. 2021

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There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.

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Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions

Cited by 8 publications

References 31 publications

Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function

Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function

Prediction models combining zonulin, LPS, and LBP predict acute kidney injury and hepatorenal syndrome–acute kidney injury in cirrhotic patients

Present and Future Therapeutic Approaches to Barrier Dysfunction

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