New Insights and Interventions for Short Bowel Syndrome

Rouch, Joshua D.; Dunn, James C.Y.

doi:10.1007/s40124-017-0119-6

Cited by 11 publications

(3 citation statements)

References 37 publications

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“…Teduglutide, a recombinant analogue of glucagon-like peptide-2 appears to be a helpful adjunct to promote bowel adaptation through increases in absorptive capacity due to its associated increase in villus height and crypt depth as well as its slowing effect on motility. 40 A broader examination of the effects of clinically useful Nrf2 inducers, 41 both drugs and food-based phytochemicals, on absorptive capacity and other intestinal functions is warranted.…”

Section: Lgr5 Olmf4mentioning

confidence: 99%

Constitutive Activation of Nrf2 in Mice Expands Enterogenesis in Small Intestine Through Negative Regulation of Math1

Yagishita

McCallum

Kensler

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Activation of Nrf2 signaling in the intestinal epithelium leads to lengthened intestines and expansion of enterogenesis, which is mediated through suppression of Notch downstream effector Math1 in enterocyte progenitor cells. This study indicates the facilitation of intestinal homeostasis by Nrf2. BACKGROUND & AIMS: Notch signaling coordinates cell differentiation processes in the intestinal epithelium. The transcription factor Nrf2 orchestrates defense mechanisms by regulating cellular redox homeostasis, which, as shown previously in murine liver, can be amplified through signaling crosstalk with the Notch pathway. However, interplay between these 2 signaling pathways in the gut is unknown. METHODS: Mice modified genetically to amplify Nrf2 in the intestinal epithelium (Keap1 f/f ::VilCre) were generated as well as pharmacological activation of Nrf2 and subjected to phenotypic and cell lineage analyses. Cell lines were used for reporter gene assays together with Nrf2 overexpression to study transcriptional regulation of the Notch downstream effector. RESULTS: Constitutive activation of Nrf2 signaling caused increased intestinal length along with expanded cell number and thickness of enterocytes without any alterations of secretory lineage, outcomes abrogated by concomitant disruption of Nrf2. The Nrf2 and Notch pathways in epithelium showed inverse spatial profiles, where Nrf2 activity in crypts was lower than villi. In progenitor cells of Keap1 f/f ::VilCre mice, Notch downstream effector Math1, which regulates a differentiation balance of cell lineage through lateral inhibition, showed suppressed expression. In vitro results demonstrated Nrf2 negatively regulated Math1, where 6 antioxidant response elements located in the regulatory regions contributed to this repression. CONCLUSIONS: Activation of Nrf2 perturbed the dialog of the Notch cascade though negative regulation of Math1 in progenitor cells, leading to enhanced enterogenesis. The crosstalk between the Nrf2 and Notch pathways could be critical for finetuning intestinal homeostasis and point to new approaches for the pharmacological management of absorptive deficiencies.

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Section: Lgr5 Olmf4mentioning

confidence: 99%

Constitutive Activation of Nrf2 in Mice Expands Enterogenesis in Small Intestine Through Negative Regulation of Math1

Yagishita

McCallum

Kensler

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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“…Short bowel syndrome (SBS) is one reason among several others for intestinal failure. SBS is often a result of extensive resection of the small intestine from complications to surgery, inflammatory bowel disease and congenital intestinal malformations [ 2 , 3 ]. The syndrome is characterized by diarrhoea, malnutrition and weight loss, and the need for, parenteral nutrition (PN) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Segmental reversal of the distal small intestine in a short bowel syndrome model in piglets showed detrimental effect on weight gain

Schmidt

Hartmann

et al. 2022

BMC Gastroenterol

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Background To investigate the effects of a reversed segment of the distal small intestine to improve weight gain in an experimental short bowel syndrome (SBS) model in piglets. Methods Twenty-four piglets underwent resection of 70% of the distal small intestine. In half of the animals a conventional anastomosis was performed, and in the other half, the distal 25 cm of the remnant jejunum was reversed before the intestinal continuity was recreated. Weight was measured daily until day 28, where the animals were euthanized. Glucagon-Like Peptide-2 (GLP-2) and Glucose-dependent Insulinotropic Peptide (GIP) was measured pre- and postoperatively at day 28. Results The group with reversal of small intestine had a significant lower weight gain at 5.26 ± 3.39 kg (mean ± SD) compared to the control group with 11.14 ± 3.83 kg (p < 0.05). In the control group greater villus height and crypt depth was found distally, and greater muscular thickness was found proximally in the intervention group. GLP-2 and GIP levels increased significantly in the control group. Conclusions Treatment of short bowel syndrome with a reversed jejunal segment of 25 cm had a detrimental effect on the weight gain.

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“…Other methods to treat SBS include surgical procedures such as longitudinal intestinal lengthening and tapering (LILT) or serial transverse enteroplasty (STEP) up to heterotopic small bowel transplantation but all of them have carried significant limitations and risks [ 21 ]. Thus, new treatment strategies should be searched and to this purpose the field of tissue engineering (TE) may be promising [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Composite Scaffolds Based on Intestinal Extracellular Matrices and Oxidized Polyvinyl Alcohol: A Preliminary Study for a New Regenerative Approach in Short Bowel Syndrome

Grandi

Stocco

Barbon

et al. 2018

BioMed Research International

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Pediatric Short Bowel Syndrome is a rare malabsorption disease occurring because of massive surgical resections of the small intestine. To date, the issues related to current strategies including intestinal transplantation prompted the attention towards tissue engineering (TE). This work aimed to develop and compare two composite scaffolds for intestinal TE consisting of a novel hydrogel, that is, oxidized polyvinyl alcohol (OxPVA), cross-linked with decellularized intestinal wall as a whole (wW/OxPVA) or homogenized (hW/OxPVA). A characterization of the supports was performed by histology and Scanning Electron Microscopy and their interaction with adipose mesenchymal stem cells occurred by MTT assay. Finally, the scaffolds were implanted in the omentum of Sprague Dawley rats for 4 weeks prior to being processed by histology and immunohistochemistry (CD3; F4/80; Ki-67; desmin; α-SMA; MNF116). In vitro studies proved the effectiveness of the decellularization, highlighting the features of the matrices; moreover, both supports promoted cell adhesion/proliferation even if the wW/OxPVA ones were more effective (p < 0.01). Analysis of explants showed a continuous and relatively organized tissue wall around the supports with a connective appearance, such as myofibroblastic features, smooth muscle, and epithelial cells. Both scaffolds, albeit with some difference, were promising; nevertheless, further analysis will be necessary.

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New Insights and Interventions for Short Bowel Syndrome

Cited by 11 publications

References 37 publications

Constitutive Activation of Nrf2 in Mice Expands Enterogenesis in Small Intestine Through Negative Regulation of Math1

Constitutive Activation of Nrf2 in Mice Expands Enterogenesis in Small Intestine Through Negative Regulation of Math1

Segmental reversal of the distal small intestine in a short bowel syndrome model in piglets showed detrimental effect on weight gain

Composite Scaffolds Based on Intestinal Extracellular Matrices and Oxidized Polyvinyl Alcohol: A Preliminary Study for a New Regenerative Approach in Short Bowel Syndrome

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