Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we ask whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion leads to expanded tuft and goblet cell populations. Sprouty2 loss induces PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this results in increased stromal IL-13+ cells. IL-13 in turn induces tuft and goblet cell expansion in vitro and in vivo. Sprouty2 is downregulated by acute inflammation; this appears to be a protective response, as VillinCre;Sprouty2F/F mice are resistant to DSS colitis. In contrast, Sprouty2 is elevated in chronic colitis and in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.

Historically, the gold standard for the treatment of congenital malformations has been planned delivery at tertiary care center with attempted post-natal repair or amelioration of the lesion. Over the last few decades however, rapid advances in imaging and instrumentation technology combined with superior knowledge of fetal pathophysiology has led to the development of novel intrauterine interventions for most common fetal anomalies.Great success has already been seen the treatment of previous devastating anomalies such as myelomeningocele (MMC), congenital cystic malformations of the lung, twin-twin transfusion, and sacrococcygeal teratomas.Although still limited, these innovative techniques have unique potential to improve outcomes in the most devastating fetal anomalies.

Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad spectrum antibiotics. We therefore investigated whether the administration of broad spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects observed in humans in order to identify potentially druggable targets to aid in the management of SBS and resulting IFALD. In zebrafish with SBS, broad spectrum antibiotics altered the microbiome, decreased inflammation, and reduced the development of hepatic steatosis. After two weeks of broad spectrum antibiotics, these fish exhibited decreased alpha diversity, with less variation in microbial community composition between SBS and sham fish. Additionally, administration of broad spectrum antibiotics was associated with decreased expression of intestinal toll-like receptor 4 (tlr4), increased expression of the intestinal gene encoding the Farnesoid X receptor (fxr), decreased expression of downstream hepatic cyp7a1, and decreased development of hepatic steatosis. SBS in zebrafish reproducibly results in increased epithelial surface area as occurs in human patients who demonstrate intestinal adaptation, but antibiotic administration in zebrafish with SBS reduced these gains with increased cell death in the intervillus pocket that contains stem/progenitor cells. These alternate states in SBS zebrafish might direct the development of future human therapies.

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Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we asked whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion led to expanded goblet and tuft cell populations. Sprouty2 loss induced PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this resulted in increased stromal IL-13+ cells. IL-13 in turn induced tuft and goblet cell expansion in vitro and in vivo. Sprouty2 was downregulated by inflammation; this appeared to be a protective response, as VillinCre;Sprouty2 F/F mice were resistant to DSS colitis. In contrast, Sprouty2 was elevated in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.

Background Gastrostomy tube (G-tube) placement is commonly performed on pediatric patients but has high rates of emergency department (ED) utilization. We hypothesized that a nurse-practitioner-driven G-tube clinic would reduce ED visits and complications and improve provider and patient satisfaction. Methods After institutional review board approval, a retrospective chart review was conducted for all patients < 18 years old undergoing G-tube placement between January 2014 and June 2018. Data collected included demographics, indication, and type of G-tube as well as ED visits, clinic visits, and outcomes up to 1-year postoperative. Surveys were distributed to providers and parents to assess attitudes toward the clinic. Results There was a decrease in the number of physician clinic visits, but there was no difference in overall 30- or 90-day ED visits after institution of the G-Tube Clinic. In the cohort of patients who had problematic G-tube-related problems, such as granulation, plugged tube, or tube dislodgement, creation of the G-Tube Clinic significantly reduced 30-day (0.37 vs. 0.07, p = .0008), 90-day (0.27 vs. 0.73, p = .0031), and 1-year (0.6 vs. 1.18, p = .014) ED visits. Surgeon and patient satisfaction were improved with clinic implementation. Conclusions Implementation of a nurse-practitioner-managed clinic resulted in reduction in 30-day, 90-day, and 1-year ED visits among patients with gastrostomy issues and is associated with high levels of patient and provider satisfaction.