SIRT1 Inhibitors Mitigate Radiation-Induced GI Syndrome by Enhancing Intestinal Stem Cell Survival

In this study, the authors demonstrated that SIRT1 inhibitors were able to mitigate some of the effects of acute radiation exposure. SIRT1 inhibitors prevented GI syndrome and protected the ISC from being depleted following abdominal irradiation.

Human ileal organoid model recapitulates clinical incidence of diarrhoea associated with small molecule drugs

In this study the authors described the characterisation of a human 3D enteroid culture model for assessing drug-induced gastro-intestinal toxicity.

Location-specific cell identity rather than exposure to GI microbiota defines many innate immune signalling cascades in the gut epithelium

A recent study established a biobank of human and murine GI organoids from tissue-resident stem cells and analysed gene expression to discover that the epithelial innate immune barrier follows a specific pattern per GI segment.

The use of organoids to study the epithelial response to secreted pro-inflammatory cytokines

A recent organoid study suggests that Nfkb2 signalling pathway may be targetable to improve intestinal inflammation.

Genome-wide epigenetic and transcriptomic characterisation of human-induced pluripotent stem cell-derived intestinal epithelial organoids

Recent developments have allowed us to generate epithelial cell-specific intestinal organoids from pluripotent stem cells, we review a study which aims to characterise these organoid cultures and compare them with cultures derived from primary intestinal epithelial cells.

A murine platform to evaluate therapies against radiation-induced gastrointestinal syndrome

Models to service radiation-induced gastrointestinal syndrome are limited, this study shows a platform to study genes linked to intestinal radiation injury

The delayed effects of acute radiation exposure within the mouse intestine

Partial-body irradiation (PBI) models with minimal (2.5% or 5%) Bone Marrow (BM) sparing results in Acute GI Damage (GI-ARS). However, it enables longer-term survival against radiation levels that would normally be lethal due to BM Toxicity enabling us to study the long-term effects of exposure.

The relationship between epithelial cell fate, microbiota composition and inflammation in the intestine

How perturbation of the homeostatic mechanisms governing epithelial cell fate in the intestine influence the gut microbiota and the susceptibility to colitis. The influence of structural proteins on key signalling pathways and their downstream transcriptional machinery are discussed.

A new paper demonstrates that BMP limits Lgr5+ stem cell number in intestinal epithelial cells

The paper demonstrates that BMP acts via Smad to transcriptionally repress a range of stem cell associated genes, including Lgr5, and that this is independent of the Wnt//??catenin signalling pathway.

New paper demonstrating the microbiota impact on cell proliferation via microRNA expression changes in intestinal epithelial stem cells

Intestinal flora are known to impact the immune system and metabolism, with chronic exposures to certain flora linked to conditions such as inflammatory bowel disease and fibrosis. Breeches of the epithelial barrier and systemic infection can lead to more acute problems such as sepsis.

Citrulline as a Biomarker of GI Toxicity

Citrulline is produced by small bowel enterocytes, with circulating citrulline levels correlating with enterocyte mass. Changes in enterocyte number (or in some cases function) are therefore reflected in plasma levels. As a result, citrulline levels may be a biomarker for various GI syndromes