Cecal Lumen Research Articles

Post‐secretory activation of Paneth cell α‐defensins in the cecal and colonic lumen of matrix metalloproteinase‐7‐null mice

In mice, Paneth cell α‐defensins, termed cryptdins (Crps), are converted intracellularly from inactive precursors to bactericidal forms by matrix metalloproteinase‐7 (MMP‐7). Because it is possible that other extracellular proteinases may be capable of similar processing, we tested whether secreted proCrps are converted to active forms in the MMP‐7−/− mouse. Protein extracts from complete (organ plus luminal contents) ileum, cecum, and colon of MMP‐7−/− and wild‐type C57Bl/6 mice were compared by gel permeation chromatography and acid‐urea (AU)‐PAGE. As anticipated, MMP‐7−/− ileum lacked appreciable levels of processed Crps. However, high levels of apparent Crps were purified from the cecum and colon of MMP‐7−/− mice. N‐terminal sequencing and mass spectrometry identified α‐defensins consisting of a mixture of native Crps, N‐terminally truncated Crps, and Crps with elongated N termini that retain proregion residues near the proregion‐Crp junction. Thus, secreted mouse proCrps may be processed in the large bowel lumen, even in the absence of the intracellular activating enzyme. Also, the MMP‐7−/− mouse may be a useful model of innate mucosal immunity in the small intestine, but the knockout is not α‐defensin deficient in cecum or distal colon, downstream from the site of precursor secretion in small intestinal crypts of Lieberkühn.Supported by NIH grants DK044632, AI059346, and AI057757.

Genetic Capability of Young Layers for Survival after Salmonella entritidis Challenge

Problem statement: Genetic line differences in resistance of layer hens and young chicks to Salmonella entritidis have been identified through a lot of studies. That is why the agricultural industry was prepared for the potential phasing out of antibiotics for use in controlling bacterial pathogens. Early infection may result in long term colonization of layers with Salmonella entritidis, resulting in shedding into table or hatching eggs. Approach: This study was carried to evaluate the genetic factors underlying early response to Salmonella entritidis, genetic line differences in mortality and pathogen load at two sites (cecal lumen and spleen) were investigated. At day of hatch, chicks of four genetic lines were intra-esophageally inoculated with one of three doses of Salmonella entritidis phage type 13 A. Results: There was a significant effect (p≤0.001) of genetic line on chick 6 days survival. The effect of genetic line was significant (p≤0.05) on survivors’ Salmonella entritidis burden in cecal content but not on Salmonella entritidis load per gram of spleen. Salmonella entritidis pathogen load of the spleen and the cecal content were not significantly correlated, indicating that independent host mechanisms are partly responsible for these two traits. Conclusion: Future Salmonella entritidis control mechanism in poultry may be the same as it is used these days but it has to be for longer term sustainability, genetic resistance should be pursued. Sufficient genetic line variation should exists to suggest that it is feasible to effectively choose among pure breeder lines for those exhibits reduced Salmonella entritidis induced mortality and cecal content Salmonella entritidis pathogen load in young layer chicks.

Cecal Infusion of Butyrate Does Not Alter Cecal Concentration of Butyrate in Piglets Fed Inulin

Cecal or distal colonic concentration of butyrate has been used as an index of butyrate production from various fermentable carbohydrates. However, we previously found that cecal concentration of butyrate does not correlate with the rate of synthesis of butyrate in the cecal lumen. As part of a larger study of the cellular effects of cecal infusions of butyrate, we sought to rule out the null hypothesis that cecal infusion of butyrate also would not alter butyrate concentration in the cecum. Piglets (n = 10) were fed sow milk replacement formula plus inulin (3 g x L(-1)). After 6 days of oral feeding, the piglets were randomly assigned into 2 equal groups: (I) Cecal infusion of phosphate-buffered NaCl and (II) cecal infusion of butyrate (2.13 micromol x kg(-1) x min(-1)). The concentration of butyrate was measured by gas chromatography in the cecum and distal colon. There was no effect of cecal butyrate infusion on butyrate concentration (mM; I vs II) in the cecum (5.7 +/- 0.4 vs 5.3 +/- 1.1) or distal colon (3.3 +/- 0.6 vs 4.1 +/- 0.8) or on the ratio of cecal butyrate concentration to the sum of the concentrations of butyrate, acetate, propionate, and valerate (0.101 +/- 0.004 vs 0.083 +/- 0.011). There was no effect of cecal butyrate infusion on the concentration of any of these short chain fatty acids. At an entry rate into the cecum within the physiological range, butyrate had no effect on cecal or distal colonic luminal concentration of butyrate.

Deconjugation and Degradation of Flavonol Glycosides by Pig Cecal Microbiota Characterized by Fluorescence in Situ Hybridization (FISH)

As the bioavailability of flavonoids is influenced by intestinal metabolism, we have investigated the microbial deconjugation and degradation of several flavonols and flavonol glycosides using the pig cecum in vitro model system developed in our group. For this model system the microbiota was directly isolated from the cecal lumen of freshly slaughtered pigs. The characterization of the cecal microbiota by fluorescence in situ hybridization (FISH) with 16S rRNA-based oligonucleotide probes confirmed the suitability of the model system for studying intestinal metabolism by the human microbiota. We have investigated the microbial degradation of quercetin-3-O-beta-d-rutinoside 1, quercetin-3-O-beta-d-glucopyranoside 2, quercetin-4'-O-beta-d-glucopyranoside 3, quercetin-3-O-beta-d-galactopyranoside 4, quercetin-3- O-beta-d-rhamnopyranoside 5, quercetin-3- O-[alpha-l-dirhamnopyranosyl-(1-->2)-(1-->6)-beta-d-glucopyranoside 6, kaempferol-3-O-[alpha-l-dirhamnopyranosyl-(1-->2)-(1-->6)-beta-d-glucopyranoside 7, apigenin 8, apigenin-8- C-glucoside (vitexin) 9, and feruloyl-O-beta-d-glucopyranoside 10 (100 microM), representing flavonoids with different aglycones, sugar moieties, and types of glycosidic bonds. The degradation rate was monitored using HPLC-DAD. The flavonol O-glycosides under study were almost completely metabolized by the intestinal microbiota within 20 min and 4 h depending on the sugar moiety and the type of glycosidic bond. The degradation rates of the quercetin monoglycosides showed a clear dependency on the hydroxyl pattern of the sugar moiety. The degradation of 2 with all hydroxyl groups of the glucose in the equatorial position was the fastest. The intestinal metabolism of di- and trisaccharides was much slower compared to the monoglycosides. The structure of the aglycone has not much influence on the intestinal metabolism; however, the type of glycosidic bond ( C- or O-glycoside) has substantial influence on the degradation rate. The liberated aglycones were completely metabolized within 8 h. Phenolic compounds such as 3,4-dihydroxyphenylacetic acid 12, 4-hydroxyphenylacetic acid 13, and phloroglucinol 18 were detected by GC-MS as main degradation products.

Effects of the In Vivo Supply of Butyrate on Histone Acetylation of Cecum in Piglets

In vitro, butyrate inhibits histone deacetylase and down-regulates expression of cyclin D1. We hypothesized that an increased entry rate of butyrate into the cecal lumen would have similar effects in vivo. We used frozen cecal tissue and data from previous studies, one showing that lactulose supplementation caused an increased rate of cecal synthesis of butyrate and decreased cecal cell proliferation and density of clostridia and the other showing that cecal cell proliferation was increased by an exogenous cecal butyrate infusion at a comparable rate. The ratio of acetylated to total histones (AH ratio) and cyclin D1 mRNA expression were measured in cecal tissue. Lactulose supplementation caused a 189% increase in the AH ratio (p = .004), which inversely correlated with cecal cell proliferation (r = -0.782; p = .008). With cecal butyrate infusion, we observed a significant decrease in histone acetylation (p = .02), which also inversely correlated with cecal cell proliferation (r = -0.797; p = .002). Cyclin D1 expression was increased 6.5-fold by lactulose feeding (p = .02) but decreased 50% with cecal butyrate infusion (p = .004). The effects on histone acetylation of increased "endogenous" butyrate production produced by lactulose feeding, but not exogenous cecal infusion of butyrate, mirror those in vitro. Thus, bacterial production and exogenous infusion of butyrate have opposite effects on histone acetylation and cyclin D1 expression, suggesting that the composition of bacterial flora may play a role in butyrate's in vivo effects on the cell cycle.

A Critical Role for Rac1 in Tumor Progression of Human Colorectal Adenocarcinoma Cells

Colorectal adenocarcinoma is the second cause of cancer mortality in developed countries. Rac1 is a member of the family of Rho GTPases that regulates many intracellular signaling pathways, including those involved in tumorigenesis, invasion, and metastasis. We have investigated the role of Rac1 in colorectal tumor progression by genetic modification of the human colorectal adenocarcinoma cell line SW620 to either overexpress Rac1 or lack Rac1 expression. Tumor behavior was studied by orthotopic injection of stably modified cell lines into the cecal wall of athymic nude mice, a model that replicates the histopathological appearance and clinical behavior of human colorectal adenocarcinoma in humans. While overexpression of Rac1 resulted in an accelerated tumorigenic process, inducing a faster mortality rate, inhibition of Rac1 completely suppressed tumor formation. These results suggest that Rac1 plays a major role in colorectal adenocarcinoma progression. Finally, interference with Rac1 function may provide an important tool to block the malignant phenotype of colorectal adenocarcinoma cells.

Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury

CD8 knockout mice depleted of natural killer (NK) cells by treatment with anti-asialoGM1 (CD8KO/alphaAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential sources of injury include bacterial dissemination, cecal ischemia, and translocation of bacterial toxins. We treated wild-type and CD8KO/alphaAsGM1 mice with imipenem after CLP to decrease bacterial dissemination. Additional mice were subjected to cecal ligation without puncture of the cecal wall or cecal ligation and removal of cecal contents. Imipenem treatment decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and exhibited significant hypothermia, metabolic acidosis, and high plasma cytokine concentrations. Wild-type mice subjected to cecal ligation without puncture also died, despite very low bacterial counts in blood, but wild-type mice subjected to cecal ligation and washout of cecal contents survived. In CD8KO/alphaAsGM1 mice subjected to CLP, imipenem treatment increased survival from 50% to 100%. After cecal ligation without puncture, long-term survival was 80-90% in CD8KO/alphaAsGM1 mice. Hypothermia, metabolic acidosis, and cytokine production were attenuated in CD8KO/alphaAsGM1 mice compared with wild-type controls. These results indicate that bacterial dissemination is not a major source of injury in wild-type mice after CLP, but the presence of gut flora in the cecal lumen is required for induction of systemic inflammation after cecal injury. CD8KO/alphaAsGM1 mice are resistant to the systemic manifestations of cecal injury.

Technical Note: Improved technique for fitting pigs with steered ileocecal valve cannulas1,2

Collection of ileal digesta to evaluate AA digestibilities has become increasingly important in swine nutrition research. Steered ileocecal valve cannulation of pigs permits total collection of ileal digesta, while still allowing normal digesta flow during noncollection periods. This technique was modified and used with 64 crossbred barrows in five trials. Our procedural changes included preoperative i.v. administration of a broad-spectrum antibiotic and nonsteroidal antiinflammatory drug, sharp incision through the muscle layers of the laparotomy wound, use of a heparinized saline lavage solution, replacement of the guide ring with a stylette, and fixing the outer cannula barrel in place with a hose clamp. The current technique involves a right flank laparotomy, parallel and distal to the last rib, with the pig under general anesthesia. A stainless-steel ring (inner ring = 2.0 mm thick, 35.0 mm i.d.) is introduced into the ileal lumen through an enterotomy proximal to the origin of the ileocecal fold. A nylon string attached to this ring is threaded through the ileum and ileocecal valve into the cecum using a silastic stylette, which encases the string. A second stainless-steel ring (outer ring = 2.0 mm thick, 34 mm o.d.) is fixed in place around the ileum, distal to the inner ring and just proximal to the ileocecal valve. A polyurethane cannula barrel (barrel = 100 mm long, 26 mm i.d., 32 mm o.d.; flange = 70 mm o.d.) is introduced into the cecal lumen via an enterotomy through the lateral cecal band and secured in place with two purse-string sutures. The cannula is exteriorized through an incision caudal and proximal to the intial laparotomy site, where it is plugged using a cylindrical stopper (26 mm o.d., 55 mm long) and held in place by a second cannula barrel (barrel = 43 mm length, 33 mm i.d., 41 mm o.d.; flange = 80 mm o.d.). Procedural changes decreased postsurgical complications, as evidenced by decreased seepage around the cannula and fewer and less severe adhesions noted at necropsy. Based on five trials, this technique is a reliable means of collecting ileal digesta for nutrient analyses.

Validity of current experimental evidence on laparoscopic surgery for colorectal cancer

Experimental animal studies can provide crucial evidence for the evaluation and refinement of the controversial area of many areas of surgery. Recently, during the surge in interest in laparoscopic surgery, in particular for colorectal cancer, 72 animal studies have been published between 1995 and 2001. However, the question remains as to which of theses data can be suitably extrapolated to the human population. Forty-five of 47 studies, which use cell suspensions, relied on percutaneous intraperitoneal injection of cancer cells to induce peritoneal carcinomatosis. One study described a laparotomy-based model with injection of tumor cells into the cecal lumen while a different study presented the cancer cells via enema. In this study, sigmoid resection was performed before colorectal solid tumor growth.

Candidate genes for resistance to Salmonella enteritidis colonization in chickens as detected in a novel genetic cross

Salmonellosis is a zoonotic disease that is problematic for both animal production and food safety. A novel genetic cross, named the Iowa Salmonella response resource population (ISRRP), was established to elucidate the genetic control of resistance to Salmonella enteritidis (SE) colonization in young chicks, to characterize unique resistance alleles, and to estimate gene interaction effects. Outbred broiler sires were mated with dams of diverse, highly inbred, light-bodied lines to produce an F 1 generation that was informative for all heterozygous alleles of the sires. Mating F 1 sires back to dams of the corresponding inbred line produced a backcross generation. To mimic the natural route of exposure and thus afford the opportunity to investigate mucosal immunity, pathogenic SE were inoculated into the esophagus of day-old chicks. After 1 week, the SE colonizing the cecal lumen and the spleen were enumerated. Candidate genes were selected for analysis based upon one of the two criteria. Functional candidates were genes with reported activity related to the tested traits. Positional candidates were genes mapped near microsatellites that were linked, in other phases of this project, with antibody levels to SE vaccine. Broiler sire alleles of the MHC class I, NRAMP1, PSAP, and IAP1 genes showed association with SE colonization in the F 1 generation of this novel disease resistance resource population.

Diversity and phylogenetic analysis of bacteria in the mucosa of chicken ceca and comparison with bacteria in the cecal lumen

We reported the first attempt to describe mucosa-associated bacterial populations in the chicken ceca by molecular analysis of 16S rRNA genes. Bacteria in the mucosa were highly diverse but mainly Gram-positive with low G+C. Fusobacterium prausnitzii and butyrate-producing bacteria comprised the largest groups among 116 cloned sequences. Twenty five percent of the clones had less than 95% homology to database sequences. Many sequences were related to those of uncultured bacteria identified in human feces or the bovine rumen. Terminal restriction fragment length polymorphism (T-RFLP) analysis revealed some differences between bacterial populations present in the mucosa and lumen of ceca. Greater resolution of bacterial population was obtained using a culture-independent approach rather than a culture-based approach.

Genetic Line Differences in Survival and Pathogen Load in Young Layer Chicks after Salmonella enterica Serovar Enteritidis Exposure

Early infection may result in long-term colonization of layers with Salmonella enterica sv. enteritidis (S. enteritidis, SE), resulting in shedding into table or hatching eggs. To evaluate genetic factors underlying early response to SE, genetic line differences in mortality and pathogen load at two sites (cecal lumen and spleen) were investigated. At day of hatch, chicks of four genetic lines were intra-esophageally inoculated with one of three doses of SE phage type 13a. There was a significant effect (P < 0.001) of genetic line on chick 6-d survival. The effect of genetic line was significant (P < 0.05) on survivors’ SE burden in cecal content but not on SE burden per gram of spleen. The SE pathogen load of the spleen and the cecal content were not significantly correlated, indicating that independent host mechanisms are partly responsible for these two traits. Genetic line differences in chick survival and SE colonization of cecal content were demonstrated in young layer chicks.

Molecular Analysis of the Microbial Diversity Present in the Colonic Wall, Colonic Lumen, and Cecal Lumen of a Pig

Molecular Analysis of the Microbial Diversity Present in the Colonic Wall, Colonic Lumen, and Cecal Lumen of a Pig

Sonographic diagnosis of intussusception of the appendix vermiformis

We present 2 cases of intussusception of the appendix vermiformis (IAV) in children. Sonographic examination demonstrated a lead point within a characteristic multiconcentric ring sign, and longitudinal sonograms showed the inverted appendix protruding into the cecal lumen. A contrast-enema study, using a water-soluble contrast medium, was performed in each case, and a “coiled-spring” sign or “spiral shell” appearance confirmed the diagnosis. A surgical reduction of the appendix and an appendectomy were performed in each case. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:492–496, 2000.

The “human”-like morphology of the swine papilla ilealis

The morphology of the ileocecocolic transition, between the small and large intestine was studied in 33 male, adult pigs of unknown breed. The results were analyzed by the Wilcoxon Test (alpha < or = 0.05). The ileum opened into the large intestine, in all of the cases, at the level of the cecocolic junction in the form of a conical papilla (ileal papilla) turned towards the large intestine, with an oblique caudal and lateral direction, pointing to the cecal lumen. The cranial contour is higher than the caudal one, with average values of 3.0 cm, and 1.5 cm in the fresh specimens and 2.8 cm and 1.4 cm after fixation of the specimens. The average diameter of the papilla apex was 1.5 cm, both in the fresh specimens and in the fixed ones. In 100% of the cases the ileal papilla appeared with a star-shaped orifice in its apex in both the fresh and in the fixed specimens. Our studies showed that the transition between the small and large intestine of the swine is ileocecocolic, thus similar to humans and different from the ileocecal (Perissodactyla, Rodentia, Lagomorpha) and, according to most descriptions, ileocolic (dog) transitions found in other animals.

Molecular analysis of the microbial diversity present in the colonic wall, colonic lumen, and cecal lumen of a pig.

Random clones of 16S ribosomal DNA gene sequences were isolated after PCR amplification with eubacterial primers from total genomic DNA recovered from samples of the colonic lumen, colonic wall, and cecal lumen from a pig. Sequences were also obtained for cultures isolated anaerobically from the same colonic-wall sample. Phylogenetic analysis showed that many sequences were related to those of Lactobacillus or Streptococcus spp. or fell into clusters IX, XIVa, and XI of gram-positive bacteria. In addition, 59% of randomly cloned sequences showed less than 95% similarity to database entries or sequences from cultivated organisms. Cultivation bias is also suggested by the fact that the majority of isolates (54%) recovered from the colon wall by culturing were related to Lactobacillus and Streptococcus, whereas this group accounted for only one-third of the sequence variation for the same sample from random cloning. The remaining cultured isolates were mainly Selenomonas related. A higher proportion of Lactobacillus reuteri-related sequences than of Lactobacillus acidophilus- and Lactobacillus amylovorus-related sequences were present in the colonic-wall sample. Since the majority of bacterial ribosomal sequences recovered from the colon wall are less than 95% related to known organisms, the roles of many of the predominant wall-associated bacteria remain to be defined.

Gas supersaturation in the cecal wall of mice due to bacterial CO2production

PCO2 in the lumen and serosa of cecum and jejunum was measured in mice. The anesthetic used was a fentanyl-fluanisone-midazolam mixture. PCO2 was recorded in vivo and postmortem. PCO2 was 409 +/- 32 Torr (55 +/- 4 kPa) in the cecal lumen and 199 +/- 22 Torr (27 +/- 3 kPa) on the serosa in normal mice. Irrigation of the cecum resulted in serosal and luminal PCO2 levels of 65-75 Torr. Cecal PCO2 was significantly lower in germ-free mice (65 +/- 5 Torr). Cecal PCO2 increased significantly after introduction of normal bacterial flora into germ-free mice. Introduction of bacterial monocultures into germ-free mice had no effect. After the deaths of the mice, cecal PCO2 increased rapidly in normal mice. The intestinal bacteria produced the majority of the cecal PCO2, and the use of tonometry in intestinal segments with a high bacterial activity should be interpreted with caution. We propose that serosal PCO2 levels >150-190 Torr (20-25 kPa) in the cecum of mice with a normal circulation may represent a state of gas supersaturation in the cecal wall.

Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: experimental bases.

During the past few years, considerable attention has been given to the impact of nutrition on kidney disease. The question arises of whether the effect of a moderate dietary protein restriction could be reinforced by enrichment of the diet with fermentable carbohydrates. Feeding fermentable carbohydrates may stimulate the extrarenal route of nitrogen (N) excretion through the fecal route. Such an effect has been reported in several species, including healthy humans and patients with chronic renal failure (CRF). Furthermore, studies of these subjects show that the greater fecal N excretion during the fermentable carbohydrate supplementation period was accompanied by a significant decrease in plasma urea concentration. In animal models of experimental renal failure, the consumption of diets containing fermentable carbohydrates results in a greater rate of urea N transfer from blood to the cecal lumen, where it is hydrolyzed by bacterial urease before subsequent microflora metabolism and proliferation. Therefore, this results in a greater fecal N excretion, coupled with a reduction in urinary N excretion and plasma urea concentration. Because elevated concentrations of serum urea N have been associated with adverse clinical symptoms of CRF, these results suggest a possible usefulness of combining fermentable carbohydrates with a low-protein diet to increase N excretion through the fecal route. Further investigations in this population of patients of whether fermentable carbohydrates in the diet may be beneficial in delaying or treating the symptoms and chronic complications of CRF will certainly emerge in the future. This should be realized without adversely affecting nutritional status and, as far as possible, by optimizing protein intake for the patients without being detrimental to renal function.

Model of implantation of tumor cells simulating recurrence in colonic anastomosis in mice.

Local recurrence after colorectal cancer surgery is usually perianastomotic. An experiment was designed to investigate whether free intraluminal cells can penetrate through a colonic anastomosis and thereby cause local recurrence. BALB/c and C57/BL mice underwent ascending colotomy followed by watertight anastomosis. Thereafter, CT-26 murine colon carcinoma cells were injected into the cecal lumen 2 cm proximal to the anastomosis of syngeneic BALB/c mice, whereas B-16 murine melanoma cells were injected in the same fashion into C57/BL mice. Control animals without anastomosis received similar injections. Animals were killed 24 hours, 72 hours, and 30 days after surgery and were checked for tumorigenesis. Results of peritoneal fluid cytology were negative after 24 hours, whereas after 72 hours cancer cells were identified in the peritoneal fluid of 80 percent of mice with colotomy and anastomosis compared with 20 percent of control mice. Thirty days after surgery, 11.1 percent of the control BALB/c mice developed pericecal tumor growth, similar to the overall rate of murine melanoma in C57/BL. In mice with anastomoses, perianastomotic tumor growth was observed in 47.5 percent of BALB/c mice (P < 0.001) and was correlated with the number of injected cells. Tumor growth reached approximately 75 percent tumor take with high cell densities, whereas in C57/BL mice no difference was found between the experimental and control groups. The findings suggest that free intraluminal cancer cells of colonic origin may penetrate through watertight anastomoses and implant on the anastomotic or peritoneal surface and initiate tumor growth. This anastomotic penetration is cell-mass dependent. The reported experimental model is simple, reproducible, and advantageous for studies of colonic anastomosis.

Dietary fiber stimulates the extra-renal route of nitrogen excretion in partially nephrectomized rats

The purpose of this study was to determine the effect of an indigestible carbohydrate/dietary fiber (the oligosaccharide/fiber blend, or O/F blend) on extra-renal nitrogen excretion in nephrectomized rats. The O/F blend provided a diversified source of soluble and insoluble fibers: 41.2% fructooligosaccharides, 26.4% insoluble oat fiber, 17.7% soy polysaccharides, 10.3% gum arabic, and 4.4% carboxymethylcellulose. Forty partially nephrectomized rats were randomized to one of four dietary treatments that varied in protein and O/F blend content. Dietary treatments were administered for 17 days (an adaptation phase of 10 days, followed by an experimental phase of 7 days) and included the following treatment groups: (1) 8% casein, 0% O/F blend, (2) 8% casein, 8% O/F blend, (3) 14% casein, 0% O/F blend, and (4) 14% casein, 8% O/F blend. Compared with nonnephrectomized normal rats ( n = 10), the nephrectomy procedure induced a marked renal insufficiency, with significant increases in plasma urea and creatinine concentrations (90% and 44%, respectively). In this model of renal insufficiency, feeding the fermentable fibers had the same effect as in previous studies in normal rats: The O/F blend increased cecal weight and cecal blood flow, leading to accelerated diffusion of blood urea into the cecal lumen (by threefold), urealysis to ammonia and protein synthesis by the microflora, and increased fecal excretion of nitrogen. The efficiency of O/F blend in stimulating the extra-renal route of nitrogen excretion was greatly enhanced by the simultaneous use of a low protein rate: Fecal nitrogen excretion accounted for 23% of total nitrogen excretion in rats fed a 14% casein diet, compared with 45% in those receiving the 8% casein diet. The increase of fecal nitrogen excretion was accompanied by an equal and significant decrease in urinary nitrogen excretion and a decrease in blood urea nitrogen. In conclusion, addition of an O/F blend to a low protein diet exerts a potent urea lowering effect in renally insufficient rats, suggesting that these dietary conditions could help delay the progression of renal failure or prevent its consequences.