Adaptation of Epithelial Ion Transport in the Short Bowel Syndrome

Schulzke, Jörg–Dieter; Fromm, Michael; Hippel, Cathrin; Sandforth, F; Menge, H.; Bentzel, Carl J.; Riecken, E. O.

doi:10.1159/000200425

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…So far, most animal models have used proximal small bowel resections [ 18 , 19 , 21 ]. However, while these models are well suited to study mucosal remodeling, anatomically they do not resemble the most common form of human SBS [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

et al. 2018

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Background Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood. Aims The aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation. Methods Male C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded. Results Unlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased. Conclusions 40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss. Electronic supplementary material The online version of this article (10.1007/s10620-018-5420-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

et al. 2018

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“…Different in vitro or in vivo methods were used for intestinal permeability testing. Transepithelial electrical resistance (TEER) measures ionic conductance of the paracellular pathway in the epithelial monolayer, while mounted tissue can be studied in Ussing chamber experiments [87][88][89][90][91][92]. Other in vitro methods determine the flow of biomolecules of different sizes from the apical to the luminal side of the cell monolayers or mounted tissue [93,94].…”

Section: Functional Assessment Of Intestinal Barrier By Intestinal Pe...mentioning

confidence: 99%

Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome

Büttner,

Blüthner,

Greif

et al. 2023

Nutrients

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Introduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Methods: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. Results: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Conclusions: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.

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"Gut-feeling" or evidence-based approaches in the evaluation and treatment of human short-bowel syndrome

Piena-Spoel

Sharman-Koendjbiharie

Yamanouchi

et al. 2000

Pediatric Surgery International

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Short bowel syndrome is the malabsorptive state that often follows extensive resection of the small intestine. Long-term survival without parenteral nutrition depends on the process of intestinal adaptation, through which the remaining small bowel gradually increases its absorptive capacity. The process of intestinal adaptation is almost exclusively luminal nutrient dependent. To date the clinical management of short bowel patients is mostly based on a 'trial and error' regimen because human data and randomised trials using trophic substances are lacking due to the small number of patients annually present in pediatric surgical centres. We evaluate here the currently available as well as some more recently developed methods of measuring intestinal absorption and adaptation in short bowel patients. New techniques such as measurements of (1) intestinal permeability and carbohydrate absorption using the sugar absorption test, (2) gastrointestinal hormone production of gastrin, cholecystokinin and peptide YY, (3) transmural potential difference of the gastrointestinal tract using electrophysiology and (4) mucosal enzyme expression of lactase and sucrase-isomaltase using immunohistochemistry were evaluated. These new techniques are promising in monitoring the process of adaptation of the remaining intestine and evaluating the effect of therapeutic interventions in patients with short bowel syndrome.

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Adaptation of Epithelial Ion Transport in the Short Bowel Syndrome

Cited by 5 publications

References 11 publications

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome

"Gut-feeling" or evidence-based approaches in the evaluation and treatment of human short-bowel syndrome

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