In short bowel syndrome, luminal factors influence adaptation in which the truncated intestine increases villus lengths and crypt depths to increase nutrient absorption. No study has evaluated the effect of adaptation within the distal intestine after intestinal separation. We evaluated multiple conditions, including Igf1r inhibition, in proximal and distal segments after intestinal resection to evaluate the epithelial effects of the absence of mechanoluminal stimulation.
Short bowel syndrome was created in adult male zebrafish by performing a proximal stoma with ligation of the distal intestine. These zebrafish with short bowel syndrome were compared to sham-operated zebrafish. Groups were treated with the Igf1r inhibitor NVP-AEW541, DMSO, a vehicle control, or water for 2 weeks. Proximal and distal intestine were analyzed by hematoxylin and eosin for villus epithelial circumference, inner epithelial perimeter, and circumference. We evaluated BrdU+ cells, including costaining for β-catenin, and the microbiome was evaluated for changes. Reverse transcription quantitative polymerase chain reaction was performed for β-catenin, CyclinD1, Sox9a, Sox9b, and c-Myc.
Proximal intestine demonstrated significantly increased adaptation compared to sham-operated proximal intestine, whereas the distal intestine showed no adaptation in the absence of luminal flow. Addition of the Igf1r inhibitor resulted in decreased adaption in the distal intestine but an increase in distal proliferative cells and proximal β-catenin expression. While some proximal proliferative cells in short bowel syndrome colocalized β-catenin and BrdU, the distal proliferative cells did not co-stain for β-catenin. Sox9a increased in the distal limb after division but not after inhibition with the Igf1r inhibitor. There was no difference in alpha diversity or species richness of the microbiome between all groups.
Luminal flow in conjunction with short bowel syndrome significantly increases intestinal adaption within the proximal intestine in which proliferative cells contain β-catenin. Addition of an Igf1r inhibitor decreases adaptation in both proximal and distal limbs while increasing distal proliferative cells that do not colocalize β-catenin. Igf1r inhibition abrogates the increase in distal Sox9a expression that otherwise occurs in short bowel syndrome. Mechanoluminal flow is an important stimulus for intestinal adaptation.
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- Nutritional and metabolic consequences of extensive bowel resection.Dig Dis. 1986; 4: 193-202
- Definitions of intestinal failure and the short bowel syndrome.Best Pract Res Clin Gastroenterol. 2016; 30: 173-185
- Analysis of late stomal complications following ostomy surgery.Ann Chir Gynaecol. 1997; 86: 305-310
- Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy.JPEN J Parenter Enteral Nutr. 2014; 38: 14S-22S
- Nutrition and fluid optimization for patients with short bowel syndrome.JPEN J Parenter Enteral Nutr. 2013; 37: 161-170
- Effects of oral versus intravenous nutrition on intestinal adaptation after small bowel resection in the dog.Gastroenterology. 1976; 70: 712-719
- Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.Am J Physiol Gastrointest Liver Physiol. 2015; 309: G135-G145
- Epithelial cell proliferation in the developing zebrafish intestine is regulated by the Wnt pathway and microbial signaling via Myd88.Proc Natl Acad Sci U S A. 2011; 108: 4570-4577
- Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome.Gut Microbes. 2013; 4: 212-221
- Morphological and molecular evidence for functional organization along the rostrocaudal axis of the adult zebrafish intestine.BMC Genomics. 2010; 11: 392
- Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample.Proc Natl Acad Sci U S A. 2011; 108: 4516-4522
- QIIME allows analysis of high-throughput community sequencing data.Nat Methods. 2010; 7: 335-336
- Search and clustering orders of magnitude faster than BLAST.Bioinformatics. 2010; 26: 2460-2461
- An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.ISME J. 2012; 6: 610-618
- UniFrac: a new phylogenetic method for comparing microbial communities.Appl Environ Microbiol. 2005; 71: 8228-8235
- A new method for non-parametric multivariate analysis of variance.Austral Ecology. 2001; 26: 32-46
docs S-b Available from: http://scikit-bio.org.
- EMPeror: a tool for visualizing high-throughput microbial community data.Gigascience. 2013; 2: 16
- Conservation evaluation and phylogenetic diversity.Biol Conserv. 1992; 61: 1-10
- SciPy: open source scientific tools for Python [Internet].(Scipy developers Available from:)http://www.scipy.org/Date: 2016
- The mucosal response in the excluded limb after jejunoileal bypass for morbid obesity.Surg Gynecol Obstet. 1981; 153: 346-350
- Relationship between the severity of diversion colitis and the composition of colonic bacteria: a prospective study.Gut Liver. 2014; 8: 170-176
- Diversion neovaginitis after sigmoid vaginoplasty: endoscopic and clinical characteristics.Fertil Steril. 2016; 105: 834-839.e1
- The pediatric intestinal mucosal microbiome remains altered after clinical resolution of inflammatory and ischemic disease.Surgery. 2016; 160: 350-358
- Successful autologous fecal transplantation for chronic diversion colitis.Tech Coloproctol. 2015; 19: 51-52
- Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis.World J Gastroenterol. 2012; 18: 4278-4287
- Teduglutide for safe reduction of parenteral nutrient and/or fluid requirements in adults: a systematic review.JPEN J Parenter Enteral Nutr. 2016; 40: 1096-1105
- The essential role of insulin-like growth factor-1 in the intestinal tropic effects of glucagon-like peptide-2 in mice.Gastroenterology. 2006; 131: 589-605
- IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations.Faseb J. 2015; 29: 2828-2842
- Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators.Am J Physiol Endocrinol Metab. 2007; 293: E460-E465
- Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I.Endocrinology. 2008; 149: 291-301
- The versatile functions of Sox9 in development, stem cells, and human diseases.Genes Dis. 2014; 1: 149-161
- Mucous fistula refeeding in premature neonates with enterostomies.J Pediatr Gastroenterol Nutr. 2004; 39: 43-45
- Mucous fistula refeeding in neonates with short bowel syndrome.J Pediatr Surg. 1999; 34: 1100-1103
- SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine.Gastroenterology. 2015; 149: 1553-1563.e10
Published online: December 20, 2016
Accepted: October 20, 2016
Supported by the 2014 CHLA CIRM Training Grant and the 2015 Broad Clinical Fellowship sponsored by the Eli and Edythe Broad Foundation.
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