scholarly journals Micromanaging the gut: unravelling the regulatory pathways that mediate the intestinal adaptive response

2018 ◽  
Vol 100 (3) ◽  
pp. 165-171 ◽  
Author(s):  
A Balakrishnan
Keyword(s):  
Small Bowel ◽  
Circadian Clock ◽  
Short Bowel Syndrome ◽  
Bowel Resection ◽  
Clock Genes ◽  
Small Bowel Resection ◽  
Glucose Absorption ◽  
Short Bowel ◽  
Massive Small Bowel Resection

Short bowel syndrome occurs following the loss of a large portion of functional intestine and is associated with high morbidity and mortality. The intestine exhibits pronounced diurnal rhythms in glucose absorption and mounts a profound proliferative response following massive small bowel resection. Understanding the molecular pathways that underpin this could yield novel treatment options. Two in vivo models were employed using the nocturnally active Sprague Dawley® rat, namely daytime feeding and massive small bowel resection. Glucose absorption exhibited a 24-hour periodicity in the gut and peaked during maximal nutrient delivery, mediated by rhythms in the glucose transporter sodium glucose co-transporter 1 (SGLT1). Feeding during the day shifted the peak in the circadian clock gene PER1 and SGLT1. RNA interference and luciferase assays demonstrated that PER1 transcriptionally regulates SGLT1, linking for the first time clock genes and intestinal glucose absorption. Intestinal proliferation also exhibited diurnal rhythmicity, with peak absorptive surface area occurring during maximal nutrient availability. mir-16 is diurnally expressed in intestinal crypts, exhibiting minimal expression during maximal nutritional availability. mir-16 overexpression increased apoptosis and arrested proliferation in vitro. mir-125a was upregulated in intestinal crypts following 80% small bowel resection, and induced apoptosis and growth arrest upon overexpression in vitro. This work provides novel insights into the role of circadian clock genes, intestinal transporters and microRNAs in regulating intestinal absorption and proliferation and is the first demonstration of a role for microRNAs in these adaptive phenomena. Modulation of these pathways may represent a new therapeutic option for the management of short bowel syndrome.

Pediatric Short Bowel Syndrome: Adaptation After Massive Small Bowel Resection

2007 ◽  
Vol 45 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Ljubomir Rossi ◽  
Padmalatha Kadamba ◽  
Claes Hugosson ◽  
Edward B De Vol ◽  
Zakaria Habib ◽  
...  
Keyword(s):  
Small Bowel ◽  
Short Bowel Syndrome ◽  
Bowel Resection ◽  
Small Bowel Resection ◽  
Short Bowel ◽  
Massive Small Bowel Resection

Massive Small Bowel Resection During Pregnancy Causing Short Bowel Syndrome

2011 ◽  
Vol 77 (12) ◽  
pp. 1589-1592 ◽  
Author(s):  
Elena Boland ◽  
Jon S. Thompson ◽  
Wendy J. Grant ◽  
Jean Botha ◽  
Alan N. Langnas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Bowel ◽  
Short Bowel Syndrome ◽  
Bowel Resection ◽  
Small Bowel Resection ◽  
Bowel Infarction ◽  
Short Bowel ◽  
Vascular Insufficiency ◽  
Massive Small Bowel Resection

Massive small bowel infarction in pregnancy is rare but has devastating complications. Diagnosis is difficult because pregnancy masks the symptoms. Our aim was to assess risk factors and outcomes of massive resection associated with pregnancy. We conducted a review of nine patients with short bowel syndrome (SBS) secondary to massive bowel resection during pregnancy. The most common cause of bowel resection was midgut volvulus in seven patients. Four of these also had malrotation. Three others had previous abdominal operations, including gastric bypass. The two remaining patients had vascular insufficiency. Five of the nine patients presented after a cesarean delivery. There were three fetal deaths. Resulting small bowel length was less than 60 cm in all but one patient. All patients required parenteral nutrition (PN). Seven patients developed significant complications related to SBS and long-term PN. Four patients underwent transplantation. Massive small bowel resection during pregnancy is a devastating complication, which requires a high degree of suspicion to diagnose. Most patients have risk factors, which include previous surgery, congenital malrotation, and a hypercoagulable state. Surviving patients usually need long-term PN or transplantation.

Stimulation of intestinal growth and function with DPP4 inhibition in a mouse short bowel syndrome model

2014 ◽  
Vol 307 (4) ◽  
pp. G410-G419 ◽  
Author(s):  
Ryo Sueyoshi ◽  
Kathleen M. Woods Ignatoski ◽  
Manabu Okawada ◽  
Bolette Hartmann ◽  
Jens Holst ◽  
...  
Keyword(s):  
Small Bowel ◽  
Short Bowel Syndrome ◽  
Plasma Levels ◽  
Bowel Resection ◽  
Small Bowel Resection ◽  
Nuclear Antigen ◽  
Intestinal Growth ◽  
Short Bowel ◽  
Time Points ◽  
Absorptive Function

Glucagon-like peptide-2 (GLP-2) has been shown to be effective in patients with short bowel syndrome (SBS), but it is rapidly inactivated by dipeptidyl peptidase IV (DPP4). We used an orally active DPP4 inhibitor (DPP4-I), MK-0626, to determine the efficacy of this approach to promote adaptation after SBS, determined optimal dosing, and identified further functional actions in a mouse model of SBS. Ten-week-old mice underwent a 50% proximal small bowel resection. Dose optimization was determined over a 3-day post-small bowel resection period. The established optimal dose was given for 7, 30, and 90 days and for 7 days followed by a 23-day washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (proliferating cell nuclear antigen), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins and GLP-2 receptor, IGF type 1 receptor, and GLP-2 plasma levels. Glucose-stimulated sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2 receptor levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time, with greater absorptive function at early time points and enhanced proliferation at later time points. Interestingly, adaptation continued in the group treated for 7 days followed by a 23-day washout. DPP4-I enhanced IEC proliferative action up to 90 days postresection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus DPP4-I treatment may prove to be a viable option for accelerating intestinal adaptation with SBS.

Short- and long-term effects of small bowel resection: a unique histological study in a piglet model of short bowel syndrome

2011 ◽  
Vol 135 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Prue M. Pereira-Fantini ◽  
Sarah L. Thomas ◽  
Guineva Wilson ◽  
Russell G. Taylor ◽  
Magdy Sourial ◽  
...  
Keyword(s):  
Small Bowel ◽  
Short Bowel Syndrome ◽  
Bowel Resection ◽  
Histological Study ◽  
Small Bowel Resection ◽  
Long Term Effects ◽  
Short Bowel ◽  
Short And Long Term

scholarly journals Hypomagnesemia in short bowel syndrome patients

2000 ◽  
Vol 118 (6) ◽  
pp. 169-172 ◽  
Author(s):  
Simone Chaves Miranda ◽  
Michelle Lizzy Bandeira Ribeiro ◽  
Eduardo Ferriolli ◽  
Júlio Sérgio Marchini
Keyword(s):  
Small Bowel ◽  
Short Bowel Syndrome ◽  
Bowel Resection ◽  
Serum Magnesium ◽  
Small Bowel Resection ◽  
University Hospital ◽  
Short Bowel ◽  
Metabolic Unit ◽  
The University

CONTEXT: Magnesium support to small bowel resection patients. OBJECTIVE: Incidence and treatment of hypomagnesemia in patients with extensive small bowel resection. DESIGN: Retrospective study. SETTING: Metabolic Unit of the University Hospital Medical School of Ribeirão Preto, University of São Paulo, Brazil. PATIENTS: Fifteen patients with extensive small bowel resection who developed short bowel syndrome. MAIN MEASUREMENTS: Serum magnesium control of patients with bowel resection. Replacement of magnesium when low values were found. RESULTS: Initial serum magnesium values were obtained 21 to 180 days after surgery. Hypomagnesemia [serum magnesium below 1.5 mEq/l (SD 0.43)] was detected in 40% of the patients [1,19 mEq/l (SD 0.22)]. During the follow-up period, 66% of the patients presented at least two values below reference (1.50 mEq/l). 40% increased their serum values after magnesium therapy. CONCLUSION: Metabolic control of serum magnesium should be followed up after extensive small bowel resection. Hypomagnesemia may be found and should be controlled.

scholarly journals Tis7 deletion reduces survival and induces intestinal anastomotic inflammation and obstruction in high-fat diet-fed mice with short bowel syndrome

2014 ◽  
Vol 307 (6) ◽  
pp. G642-G654 ◽  
Author(s):  
Amy M. Garcia ◽  
Derek Wakeman ◽  
Jianyun Lu ◽  
Christopher Rowley ◽  
Taylor Geisman ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Small Bowel ◽  
Short Bowel Syndrome ◽  
High Fat Diet ◽  
Adaptive Response ◽  
Bowel Resection ◽  
Control Diet ◽  
Small Bowel Resection ◽  
High Fat ◽  
Short Bowel

Effective therapies are limited for patients with parenteral nutrition-dependent short bowel syndrome. We previously showed that intestinal expression of the transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7 ( tis7) is markedly increased during the adaptive response following massive small bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we further explore the functional implications of tis7 deletion in intestinal lipid metabolism and the adaptive response following small bowel resection. Intestinal tis7 transgenic ( tis7tg), tis7−/−, and wild-type (WT) littermates were subjected to 50% small bowel resection. Mice were fed a control or a high-saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery, lipid absorption, mucosal lipid analysis, and the morphometric adaptive response were analyzed. Quantitative real-time PCR was performed to identify tis7 downstream gene targets. Postresection survival was markedly reduced in high-fat, but not control, diet-fed tis7−/− mice. Decreased survival was associated with anastomotic inflammation and intestinal obstruction postresection. High-fat, but not control, diet-fed tis7−/− mice had increased intestinal IL-6 expression. Intestinal lipid trafficking was altered in tis7−/− compared with WT mice postresection. In contrast, high-fat diet-fed tis7tg mice had improved survival postresection compared with WT littermates. High-fat diet feeding in the setting of tis7 deletion resulted in postresection anastomotic inflammation and small bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may require tis7 and its target genes. The presence of luminal fat in the setting of tis7 deletion promotes an intestinal inflammatory response postresection.

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