Understanding and augmenting human intestinal adaptation: a call for more clinical research

Tavakkolizadeh, Ali; Whang, Edward E.

doi:10.1177/0148607102026004251

Cited by 30 publications

(18 citation statements)

References 8 publications

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“…The present study clearly shows adaptive morphological changes, with significantly deeper crypts (ϩ35%) and increased numbers of cells (ϩ22%) per crypt, suggesting that the absorptive surface was increased in the colon after massive and distal small bowel resection. A previous study did not document such morphological changes in the colon of three patients with SBS with type II (jejuno-colonic anastomosis), but the median time since constitution of these patients was less than 2 yr (50,55). In animal models with small bowel resection, the adaptive response is temporally regulated that confirms the importance of studying time (15).…”

Section: Discussionmentioning

confidence: 80%

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Joly¹,

Mayeur²,

Messing³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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, although a remaining colon improves patient outcome, there is no direct evidence of a mucosal colonic adaptation in humans. This prospective study evaluates morphology, proliferation status, and transporter expression level in the epithelium of the remaining colon of adult patients compared with controls. The targeted transporters were Na ϩ /H ϩ exchangers (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and compared with 11 healthy controls. The depth of crypts and number of epithelial cells per crypt were quantified. The proliferating and apoptotic cell contents were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs, and PepT1 protein were quantified by quantitative RT-PCR and Western blot, respectively. In patients with SBS compared with controls, 1) hyperphagia and severe malabsorption were documented, 2) crypt depth and number of cells per crypt were 35% and 22% higher, respectively (P Ͻ 0.005), whereas the proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified distally, and PepT1 mRNA and protein were unmodified. We concluded that, in hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes include an increased absorptive surface with an unchanged proliferative/apoptotic ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is the first study showing a controlled nonpharmacological hyperplasia in the colon of patients with SBS.

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Section: Discussionmentioning

confidence: 80%

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Joly¹,

Mayeur²,

Messing³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…For example, application of growth factors in enhancing the absorptive capacity of remnant intestine has had promising results in some animal models; however, there has been little success in the clinical setting (2). Another approach has been the use of intestinal transplantation for patients with SBS, but the current results are poor, with reported graft survival rates of less than 50% at 2 years (3).…”

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confidence: 99%

Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography1

et al. 2003

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“…99,100 Several studies aiming to elucidate the basis of the adaptation response showed that digestive and absorptive properties are increased coordinately with the expression of enteroendocrine genes. [101][102][103] Peptides derived from proglucagon, an adaptation response marker, act as humoural mediators; ileal levels of proglucagon increase after small intestine resection. Proglucagon messenger RNA (mRNA) levels increase specifically in the ileum.…”

Section: Cell Differentiation and Intestinal Adaptationmentioning

confidence: 99%

Isolated ileal interposition in enteroendocrine L cells differentiation

et al. 2011

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INTRODUCTION:Due to the progressive nature of type 2 diabetes, its complexity and drug treatment perpetuity, there is currently a search for surgical procedures that can promote euglycemia also in non-obese patients. Diabetic patients glycemic control can be achieved by increasing the blood concentration of GLP-1, a hormone produced by L cells that are more densely concentrated in the terminal ileum. Early and extended improvement of diabetes in patients submitted to bariatric surgeries awakened the necessity of investigating the isolated ileal interposition as surgical alternative for the treatment of diabetes. The interposition of this ileal segment to a more anterior region (proximal jejunum) can promote a greater stimulation of the L cells by poorly digested food, increasing the production of GLP-1 and reflecting on glycemic control. However, in order to consolidate the ileal interposition as a surgical treatment of diabetes it is necessary that the interposed ileum keep the same differentiation rate into L cells for a long period to justify the intervention. AIMS:To investigate the isolated ileal interposition influence on the differentiation of intestinal precursor cells into enteroendocrine L cells over time. METHODS:Twelve 12-week-old male Wistar rats (Rattus norvegicus albinus) of the WAB strain (heterogeneous) will be used. All animals will receive a high-calorie, high-fat diet for 16 weeks or more until they develop glucose dysmetabolism confirmed by glycemic test. They will be divided into two groups of 10 animals each: the isolated ileal interposition group (GI) and the control group (GC), comprising animals that will not be submitted to any surgical intervention.Blood samples will be collected under anesthesia at the weeks 12, 26, 36 and 44 for the determination of serum levels of glucose, insulin, GLP-1, glucagon, C-peptide and glycosilated hemoglobin. The insulin tolerance test will be performed and insulin resistance will be calculated. For the comparative analysis of the ileal precursor cells differentiation into enteroendocrine cells among the two groups, the following intestinal fragments will be collected after euthanasia: interposed ileum and remaining ileum from GI, jejunum and ileum from GC. These fragments will be analyzed by imunofluorescence and also by Real Time PCR using PCR Arrays for target genes including the main ones related to stem cell, stem cell singnalling, diabetes, Wnt and Notch signaling pathways and other genes and pathways involved in the differentiation of intestinal precursor cells into enteroendocrine cells, especially GLP-1-producing L cells that play important role in euglycemia.

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Understanding and augmenting human intestinal adaptation: a call for more clinical research

Cited by 30 publications

References 8 publications

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography1

Isolated ileal interposition in enteroendocrine L cells differentiation

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