Short Bowel Group Research Articles

Short bowel upregulates oxalate and citrate transporters and increases CaOx crystal deposition in the rat hyperoxaluric kidney

Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism related to intrarenal changes is unclear. Here we examine SB may affect oxalate and citrate handlings on calcium oxalate (CaOx) crystal formation in the hyperoxaluric kidney. SB was induced by small intestine resection in male Wistar rats. Sham‐operation was performed the same surgery without resection. After 7 days of recovery, rats were then fed with 0.75% ethylene glycol (EG and SB+EG groups) for 28 days as a hyperoxaluric induction. The corresponding controls were fed with distilled water (control and SB groups). Blood and 24 h of urine were collected for analysis. Renal CaOx deposition was examined by Pizzolato’s staining. Oxalate transporters Slc26a2 and Slc26a6, and citrate transporter sodium‐dependent dicarboxylate cotransporter NaDC‐1 at their mRNA levels were examined (n=6 in each group). After 7 days of SB, hypocalciuria and hypocitraturia were found when compared with those in sham‐operated control rats. These were associated with hypocalcemia and low renal NaDC‐1 expression after 28 days. SB aggravated EG‐mediated CaOx crystal nephropathy by fostering hyperoxaluria, degree of supersaturation, and CaOx crystal deposition. Renal expression of Slc26a6 but not Slc26a2 was increased in SB+EG group when compared to those in EG or SB group. SB lowered NaDC‐1 expression, but it was reversed in SB+EG group. Intestinal expression of these transporters was similar among groups. We conclude that SB enhances CaOx crystal formation in the hyperoxaluric kidney. More oxalate and less citrate secretion due to Slc26a6 upregulation and insufficient NaDC‐1 expression, respectively, possibly contribute to the aggravated effect of SB on crystal formation.Support or Funding InformationThis research was supported by grants of the Far Eastern Memorial Hospital (FEMH‐2018‐C‐046, Tseng YS and Ma MC) and the Ministry of Science and Technology (MOST108‐2314‐B‐030‐004‐MY3, Ma MC), Taiwan.Hyperoxaluria and hypocitraturia in the short bowl (SB)‐treated hyperoxlauric rats.More prominent hyperoxaluria (A) and oxalate transporter Slc26a6 upregulation (B) was seen in the SB+EG group. Hypocitraturia were found in the SB group (C), this associated with citrate transporter NaDC‐1 downregulation (D). SB increased CaOx formation in the hyperoxaluric kidney (E). N=6 in each group. *P<0.05, EG vs. C group; #P<0.05, SB+EG vs. EG group; @P<0.05, SB+EG vs. SB groupFigure 1

The effect of probiotics on ıntestinal motility in an experimental short bowel model.

PurposeTo investigate the effect of probiotics on spontaneous contractions of smooth muscle isolated from jejunum and ileum of rat model.MethodsFour rat groups were created (n=8, in each) including control (Group 1), control+probiotic (Group 2), short bowel (Group 3), and short bowel+probiotic (Group 4). Groups 1 and 2 underwent sham operation, Groups 3 and 4 underwent massive bowel resection. Bifidobacterium Lactis was administered in Groups 2 and 4 daily (P.O.) for three weeks. On postoperative week 3, rats were sacrificed, and jejunum and ileum smooth muscle were isolated for organ bath. Muscle contraction changes were analyzed before and after addition of antagonists.ResultsShort bowel group exhibited increased amplitude and frequency of spontaneous contractions. The addition of probiotics significantly decreased enhanced amplitude and frequency of bowel contraction in short bowel group and returned to control values. L-NNA increased amplitude and frequency of contractions in all groups. While indomethacin and nimesulide increased the amplitude in all groups, the frequency was only increased in jejunum. Hexamethonium and tetrodotoxin did not change the contraction characteristics in all groups.ConclusionWe suggest that early use of probiotics may significantly regulate bowel motility, and accordingly improve absorption of nutrients in short bowel syndrome.

Outcomes of intestinal failure—a comparison between children with short bowel and dysmotile intestine

Background We investigated whether mortality, intestinal adaptation, and liver function differ between intestinal failure (IF) patients with either short bowel (SB) or bowel dysmotility (DM). Patients and methods Twenty-six consecutive patients with SB (n = 20) or DM (n = 6) treated between 2000 and 2007 were retrospectively assessed. Intestinal failure was defined as less than 25% of age-adjusted small intestinal length or dependence on parenteral nutrition (PN) more than 6 months. Results Median age-adjusted small intestinal length (17% vs 45%) and gestational age (35 vs 40 weeks) were ( P < .05) shorter, whereas proportion of the remaining colon (86% vs 0%) was ( P < .05) higher in the SB group relative to the DM group. Overall survival was 92%. Median peak serum bilirubin (80 vs 25 μmol/L) and rate of cholestasis (11/20 vs 0/6) were higher ( P < .05) in the SB group. Short bowel rather than DM as an etiology of IF predicted weaning off PN (RR, 39.3; 95% confidence interval [CI], 1.43-526; P < .01) and development of cholestasis (risk ration [RR], 18.3; 95% CI, 0.658-127; P < .05). Three SB children developed liver failure and two died, whereas neither of these occurred in the DM group. Conclusions Children with SB are more likely to wean off PN but more prone to cholestatic liver disease than those with DM as an etiology of IF.

Energy absorption as a measure of intestinal failure in the short bowel syndrome.

Energy absorption from a liquid test meal, intestinal transit rate and water and sodium output over a six hour period were measured in five patients with an ileostomy and 12 patients with the short bowel syndrome, five of whom were on longterm parenteral nutrition. The proportion of total energy absorbed was greatest in the ileostomists (median 87%, range 82-92%), less in short bowel patients not on parenteral nutrition (median 67%, range 59-78%, p less than 0.01) and least in the short bowel group who needed it (median 27%, range 2-63%, p less than 0.01). Transit rate was more rapid in the short bowel patients compared with the ileostomists. A close correlation was observed between percentage energy absorption and the dry weight of the stools/stoma effluent collected during the six hour test period (r = -0.99, p less than 0.001). This simple non-invasive test quantitates the degree of intestinal failure and may be of practical help in management.

Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans

The urinary excretion of 3-methylhistidine (3MEH) in humans and animals has been used as a biologic marker for skeletal muscle protein breakdown. In rats, it has been recently suggested that there is a significant contribution of 3MEH in urine from the gastrointestinal tract due to the rapid turnover of protein in that tissue. To evaluate this point in humans, six patients with short bowel were evaluated. They were placed on three-day meat-free diets while 24-hour urine collections were obtained. The mean ± SEM 3MEH in the short-bowel group was 3.27 ± 0.34 μmol/kg/d and the mean ± SEM molar ratio of 3MEH to creatinine was 0.0212 ± 0.0012. These data were not significantly different from the control group at 95% confidence level. The results suggest that the contribution of the small intestine appears to be negligible, therefore urinary 3MEH should continue to be a valid index of skeletal muscle breakdown in man.

Small intestine transplantation: A logical solution for short bowel syndrome?

The purpose of this study is to determine whether small intestine transplantation could be considered as an alternative treatment in infants and children with short bowel syndrome. The potential nutritional consequence of orthotopic small intestine transplantation was evaluated in a rat model. Young Lewis strain rats (weighing 250 to 275 g) were used. Lewis rats with resection of 90% of the small intestine were studied as short bowel group (group I, n = 5). In the transplant group rats, 90% of the original small intestine was transplanted orthotopically using microvascular techniques (group II, n = 5). During the study period of 8 weeks, group II gained weight at rates equal to that of normal age matched rats (+30% of the preoperative weight), whereas rats with short bowel (group I) lost 10% of their weight. Two weeks following transplantation, serum albumin levels were maintained in the normal range in group II. However, group I rats showed decreased albumin levels. Serum cholesterol levels showed no significant difference between the two groups. Maltose absorption was evaluated as a functional test of small intestinal graft absorption (1.0 mg/g body weight of maltose was orally administered, and serum glucose levels were measured). The glucose level at 45 minutes was significantly blunted in group I in comparison with group II. The data from this study suggested that small intestine transplantation can produce adequate nutritional support to sustain growth and development in this rat model. It would be anticipated that small intestine transplantation in patients with short bowel syndrome would also benefit nutritionally.

Home parenteral nutrition for management of the severely malnourished adult patient

Nineteen adult patients with severe malnutrition received cyclic nocturnal home parenteral nutrition (HPN) for a total duration of 485 patient-months. Malnutrition had resulted from severe short bowel syndrome (13 patients), extensive Crohn's disease (4 patients), amyloidosis with pseudoobstruction (1 patient), and a combination of celiac sprue and a Whipple procedure (1 patient). The length of small bowel remaining in the short bowel group ranged from 0 to 155 cm with an average of 80 cm. Nutritional indices before HPN included mean weight/ height of 72% of ideal; serum albumin, 2.6 g/dl; urinary creatinine/height index, 51 ± 22% of ideal; urinary nitrogen of only, 3.7 ± 1.6 g/day; and depressed serum measurements of electrolytes and macroelements. After the patients had received HPN for an average of 25.5 mo (3–90 mo), weight was usually normalized (mean of 95% ideal body weight) and nutritional indices—visceral protein (mean increase in albumin of 1.1 g/dl), skeletal muscle mass (increase in urinary creatinine/height index from 51% to 93% of ideal), and serum macroelements and electrolytes —confirmed improvement. Serial studies of body composition in 4 patients showed that distribution of weight gain was equally distributed between fat and lean body mass. Six of 7 patients who had residual Crohn's disease of the small bowel when HPN was begun required additional surgery for the disease. Twelve of 18 surviving patients have been socially rehabilitated; 6 patients are still disabled by combinations of their primary disease, narcotic dependence, and depression. Major complications included damage to the external segment of nine catheters, which were repaired on an outpatient basis, and four documented catheter-related infections—one infection per 10 patient-years of HPN. The benefit-to-risk ratio for HPN is high, and the method is now the treatment of choice for patients who have little hope of having adequate nutrition restored by oral means.