Distal Small Bowel Resection Yields Enhanced Intestinal and Colonic Adaptation

Tecos, Maria E.; Steinberger, Allie E.; Guo, Jun; Warner, Brad W.

doi:10.1016/j.jss.2021.11.015

Cited by 4 publications

(1 citation statement)

References 32 publications

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“…The overall goal in treating IF is to achieve enteral autonomy through intestinal adaptation so as to shorten PN duration and to prevent the associated complications, such as intestinal failure-associated liver disease (IFALD) [ 19 ]. In animal models, a wealth of functional and morphometric adaptive responses has been described, including increased cellular proliferation and angiogenesis that may stimulate mucosal growth and enhance absorptive capacities [ 20 , 21 ]. Additionally, some animal studies have also shown that intestinal adaptation may be associated with the increased expression of transporters critically important in nutrient, electrolyte, and water absorption (e.g., sodium glucose, Na/H exchangers), even independently of the increase in enterocyte mass [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of KLF4 Leading to Functional Deficit in Pediatric Patients with Intestinal Failure and Potential Therapeutic Strategy Using Decanoic Acid

et al. 2023

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Pediatric intestinal failure (IF) is the reduction in gut function to below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. The overall goal in treating IF is to achieve intestinal adaptation; however, the underlying mechanisms have not been fully understood. In this study, by performing single-cell RNA sequencing in pediatric IF patients, we found that decreased Kruppel-Like Factor 4 (KLF4) may serve as the hub gene responsible for the functional deficit in mature enterocytes in IF patients, leading to the downregulation of solute carrier (SLC) family transporters (e.g., SLC7A9) and, consequently, nutrient malabsorption. We also found that inducible KLF4 was highly sensitive to the loss of certain enteral nutrients: in a rodent model of total parenteral nutrition mimicking the deprivation of enteral nutrition, the expression of KLF4 dramatically decreased only at the tip of the villus and not at the bottom of crypts. By using IF patient-derived intestinal organoids and Caco-2 cells as in vitro models, we demonstrated that the supplementation of decanoic acid (DA) could significantly induce the expression of KLF4 along with SLC6A4 and SLC7A9, suggesting that DA may function as a potential therapeutic strategy to promote cell maturation and functional improvement. In summary, this study provides new insights into the mechanism of intestinal adaptation depending on KLF4, and proposed potential strategies for nutritional management using DA.

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