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

Abstract

, 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.

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

“…Rarefaction curves for each sample were parallel or approaching parallel, with and a piglet SBS model, the colon is known to play a critical role in determining clinical outcome, and significant morphological adaptation of the colonic mucosa has been observed following resection. [9][10][11] However, the actual impact of changes in the microbiota on the colon itself is poorly understood. Anecdotal evidence suggests that changes in the composition of the colonic microbiota contribute to the generation of symptoms including malnutrition due to decreased bile acid deconjugation, insufficient breakdown of nutrients and diarrhea and play a key role in development of serious complications such as septicaemia.…”

Microbiota matures colonic epithelium through a coordinated induction of cell cycle-related proteins in gnotobiotic rat

“…These events led to a controlled homeostasis of the colonic epithelium in response to the presence of a complex intestinal microbiota. We have recently also observed a controlled hyperplasia of the colonic epithelium in human patients with short bowel syndrome, displaying a drastic change of microbiota composition (17,18). The preservation of homeostatic balance is also crucial in protecting intestine from injury such as chemical challenges or radiation (39).…”

Morphological and functional changes in the colon after massive small bowel resection

“…In a recent report, Joly et al [19] described increased cell numbers and crypt depth within colonic crypts of SBS patients. Interestingly, proliferation and apoptosis activity was unchanged [19].…”