Experimental short-bowel syndrome: effect of an elemental diet supplemented with short-chain triglycerides.

To determine whether short-chain triglycerides (SCTs, 1:1 triacetin:tributyrin, wt:wt) enhance intestinal adaptation in short-bowel syndrome (SBS), male Sprague-Dawley rats underwent 60% distal small-bowel resection with cecectomy and received either a chemically defined diet (CD) or a CD containing 40% of nonprotein energy as either medium-chain triglycerides (MCTs) or SCTs. After 12 d the SCT group had significantly increased jejunal mucosal weight compared with the MCT and CD groups and had significantly increased segment weight and mucosal protein compared with the CD group. In the colon the SCT group had significantly increased segment and mucosal weights and mucosal protein and DNA compared with both the MCT and CD groups. Body-weight change and measurements of serum ketones, albumin, glucose, and triglycerides revealed no significant differences among groups. SCTs improved jejunal and colonic adaptive growth and maintained comparable nutritional status in SBS when compared with CD alone or CD with MCTs.

Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.

When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.

Effect of liquid formula diets supplemented with citrus pectin on intestinal structure and function.

Three studies in rats and one in normal humans subjects have documented improvements in both colonic structure and function in different conditions of colonic dysfunction. It is suggested that studies be performed in patients with colonic dysfunction to confirm these observations.

Isotonic tube feeding formula induces liquid stool in normal subjects: reversal by pectin.

Diarrhea is one of the most common complications in patients who receive tube-feeding formulas. Since the colon is the final site of water and electrolyte absorption and ultimately determines fecal composition, diarrhea during tube feeding may result from altered colonic function. The lack of dietary fiber, such as pectin, in tube-feeding formulas may be one of the means by which colonic function is affected. The purpose of this study was to determine the effect of a standard, liquid, commercially available, isotonic tube-feeding formula (ITFF) and the effects of supplementing the ITFF with pectin on colonic function as measured by stool consistency and colonic fluid composition in 13 normal adults. Data were obtained when subjects consumed their regular diet, ITFF, and ITFF supplemented with pectin using the technique of in vivo dialysis of colonic fluid. Ingestion of the ITFF resulted in a significant increase in the percentage of liquid stools compared to a regular diet [median (interquartile range) = 0% (0), 60% (64); p less than 0.01]. Ingestion of the ITFF also resulted in significant decreases in the concentrations of sodium, potassium, and short-chain fatty acids, and increases in pH and osmotic gap in colonic fluid compared to the subjects' regular diet. Supplementing the ITFF with pectin significantly reduced the incidence of liquid stools [0% (0)] and promoted a normalization of colonic fluid composition. The results suggest that the addition of pectin may enhance tolerance to ITFFs.

The effect of pectin on hepatic lipogenesis in the enterally-fed rat.

The fermentation of pectin by colonic bacteria produces short-chain fatty acids (SCFA) which are then absorbed by the host. The purpose of this study was to determine whether pectin, added to a chemically defined diet, would increase hepatic lipogenesis and whether this effect is mediated by intestinal bacteria. Eighteen Sprague-Dawley rats underwent placement of a feeding gastrostomy and a swivel apparatus. Postoperatively, rats were randomly assigned to one of three groups: 1) No Pectin received a fat-free chemically defined diet, 2) Pectin received the same diet with the addition of 1% (w/v) pectin, and 3) Neomycin received the same diet with 1% w/v pectin and neomycin (80 mg/kg of body weight daily). On the 5th postoperative d, all diets included 12.5% (v/v) deuterium as D2O. After the infusion of the labeled diets for 24 hr, the content and deuterium enrichment of liver palmitate, stearate and oleate were measured and the production rates calculated. The liver content and production rates of these fatty acids were higher in Pectin animals than in either the No Pectin or Neomycin animals. Since the effect of pectin on hepatic lipogenesis was reduced by the concomitant administration of the intestinal antibiotic neomycin, it appears that this effect depends on the bacterial fermentation of pectin. It is postulated that the SCFA produced during pectin fermentation promote lipogenesis via a direct stimulatory effect, in addition to being carbon donors.

In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.

Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection.

After massive small bowel resection, total parenteral nutrition (TPN) is prescribed to maintain nutritional status. However, TPN reduces the mass of the remaining intestinal mucosa, whereas adaptation to small bowel resection is associated with increased mucosal mass. Short-chain fatty acids (SCFAs) have been shown to stimulate mucosal cell mitotic activity. This study determined whether the addition of SCFAs to TPN following small bowel resection would prevent intestinal mucosal atrophy produced by TPN. Adult rats underwent an 80% small bowel resection and then received either standard TPN or TPN supplemented with SCFAs (sodium acetate, propionate, and butyrate). After 1 wk, jejunal and ileal mucosal weights, deoxyribonucleic acid, ribonucleic acid, and protein contents were measured and compared with the parameters obtained at the time of resection. Animals receiving TPN showed significant loss of jejunal mucosal weight, deoxyribonucleic acid, ribonucleic acid, and protein and ileal mucosal weight and deoxyribonucleic acid after small bowel resection, whereas animals receiving SCFA-supplemented TPN showed no significant change in the jejunal mucosal parameters and a significant increase in ileal mucosal protein. These data demonstrate that SCFA-supplemented TPN reduces the mucosal atrophy associated with TPN after massive bowel resection and thys may facilitate adaptation to small bowel resection.

Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis.

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.

Comparison of parenteral nutrition and enteral feeding with pectin in experimental colitis in the rat.

The effect of a pectin-supplemented enteral diet on experimental colitis was compared with parenteral nutrition and with a pectin-free enteral diet. Forty-five rats had feeding catheters placed into either the stomach (IG, n = 31) or the superior vena cava (IV, n = 14) and then received acetic acid (colitis) or saline (control) enemas. After the enema, all rats received the same diet, either IG or IV, for 6 d except for 15 rats (IGP, 9 colitis and 6 controls), which had 1% pectin added to the diet. At the end of the feeding period the IGP group had significantly less colonic inflammation and/or necrosis than either IV (p less than 0.03) or IG (p less than 0.04) groups. Nitrogen balance, serum albumin, total iron-binding capacity and body weight did not differ significantly among dietary regimens. Thus, the degree of bowel injury in experimental colitis was decreased when animals were fed a pectin-supplemented enteral diet and this effect was independent of nutritional status.

Small bowel disaccharidase activity in the rat as affected by intestinal resection and pectin feeding.

This study investigated the effects of small bowel resection (SBR) and a pectin-supplemented elemental diet (ED) on intestinal disaccharidase activity. Rats underwent placement of feeding gastrostomy and swivel apparatus. Control animals were returned to their cages while resected animals underwent an 80% SBR. Postoperatively, animals received either a pectin-free ED or the ED supplemented with 2% pectin. After 2 wk jejunal and ileal mucosal sucrase, maltase, and lactase activities and protein content were determined. Feeding the ED after SBR resulted in significant increases in all three ileal segmental disaccharidase activities but only maltase activity was significantly increased in the jejunum. The pectin-supplemented ED, however, significantly enhanced the adaptation of jejunal and ileal segmental sucrase, maltase, and lactase activity to SBR with the increase in all three jejunal disaccharidase activities being significantly greater than that of the resected animals fed the ED alone.

Application of electromagnetic and sound waves in nutritional assessment.

Four relatively new techniques that apply electromagnetic or sound waves promise to play a major role in the study of human body composition and in clinical nutritional assessment. Computerized axial tomography, nuclear magnetic resonance, infrared interactance, and ultrasonography provide capabilities for measuring the following: total body and regional fat volume; regional skeletal muscle volume; brain, liver, kidney, heart, spleen, and tumor volume; lean tissue content of triglyceride, iron, and high-energy intermediates; bone density; and cardiac function. Each method is reviewed with regard to basic principles, research and clinical applications, strengths, and limitations.

Harry M. Vars award. The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection.

The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection in the rat was investigated in this study. Sixty adult Sprague-Dawley rats underwent placement of a feeding gastrostomy and swivel apparatus. Control animals (N = 16) were then returned to their cages while the remaining animals underwent an 80% small bowel resection and anastomosis (resected, N = 44). Postoperatively, animals were randomly assigned to receive either a fat- and fiber-free elemental diet (no pectin) or the same diet supplemented with 2% pectin (pectin). After 8 days of full strength diet, samples of jejunum, ileum, and colon were obtained for analysis. The weights per unit length of the ileum and colon were significantly greater in the resected pectin group than either the resected no pectin or pectin control groups. Mucosal parameters (unit weight, DNA, RNA, and protein content) were significantly increased in the jejunum and ileum of both the resected pectin and resected no pectin groups relative to their respective control groups. However, jejunal and ileal mucosal parameters were significantly greater (1.3- to 2-fold) for the resected pectin group than for the resected no pectin group. All the mucosal parameters of the colons were significantly greater for the pectin resected group than for the pectin control group, while only colonic mucosal RNA was significantly greater for the no pectin resected group than for the no pectin control group. These data indicate that the addition of pectin to an elemental diet significantly enhanced intestinal adaptation to massive small bowel resection in the rat.

The effect of enteral feedings supplemented with pectin on the healing of colonic anastomoses in the rat.

The effect of the addition of pectin to an elemental diet on the healing of experimental colonic anastomoses was investigated. Transection and anastomosis of the ascending colon and feeding gastrostomy were performed in 24 Sprague-Dawley rats. All rats then received an elemental diet, and 12 of them had 1% (w/v) citrus pectin added to their diet. On the seventh postoperative day, animals that received pectin-supplemented diets had significantly greater bursting pressures at the anastomoses (266 versus 234 mm Hg, p less than 0.04) and significantly lower colonic mucosal pH (6.2 versus 6.8, p less than 0.001) than animals that received the elemental diet only. The colons from animals fed pectin also had significantly higher hydroxyproline content at the anastomosis than those of the control animals (46.6 versus 40.7 micrograms hydroxyproline nitrogen/mg tissue nitrogen, p less than 0.05). The decreased intracolonic pH is consistent with the hypothesis that improved healing is a local effect mediated by the presence of short-chain fatty acids resulting from the fermentation of pectin.

Identification of experimentally induced colitis by in vitro nuclear magnetic resonance.

The present study determined whether in vitro nuclear magnetic resonance could be used to assess experimentally induced colitis in rats. Acute colitis was induced in 6 Sprague-Dawley rats by acetic acid enema, while 6 control animals received saline enemas. All animals were sacrificed 24 hours post-enema, and NMR relaxation times, T1 and T2, of colonic samples were determined on a 10 MHz spin analyzer (RADX, Houston, TX). Colonic water content was determined on the same samples by desiccation. Colitis animals showed significantly higher T1 and T2 relaxation times and tissue water content than controls. T1 and T2 times correlated significantly with tissue water content. Twelve additional animals were studied histologically, six of which received acetic acid enemas and showed extensive transmural colitis. Our results suggest that in vivo proton NMR might be a useful means of non-invasively assessing the degree of colonic inflammation.