The olfactory system of migratory adult sea lamprey (Petromyzon marinus) is specifically and acutely sensitive to unique bile acids released by conspecific larvae.

Larval sea lamprey inhabit freshwater streams and migrate to oceans or lakes to feed after a radical metamorphosis; subsequently, mature adults return to streams to spawn. Previous observations suggested that lamprey utilize the odor of conspecific larvae to select streams for spawning. Here we report biochemical and electrophysiological evidence that this odor is comprised of two unique bile acids released by larvae. High performance liquid chromatography and mass spectrometry demonstrated that larval sea lamprey produce and release two unique bile acids, allocholic acid (ACA) and petromyzonol sulfate (PS). Electro-olfactogram (EOG) recording also demonstrated that the olfactory system of migratory adult sea lamprey is acutely and specifically sensitive to ACA and PS; detection thresholds for these compounds were approximately 10(-12) M. ACA and PS were the most potent of 38 bile acids tested and cross-adaptation experiments suggested that adult sea lamprey have specific olfactory receptor sites associated with independent signal transduction pathways for these bile acids. These receptor sites specifically recognize the key substituents of ACA and PS such as a 5 alpha-hydrogen, three axial hydroxyls, and a C-24 sulfate ester or carboxyl. In conclusion, the unique lamprey bile acids, ACA and PS, are potent and specific stimulants of the adult olfactory system, strongly supporting the hypothesis that these unique bile acids function as migratory pheromones in lamprey.

Consumption of prunes as a source of dietary fiber in men with mild hypercholesterolemia.

Forty-one free-living adult men with mild hypercholesterolemia (5.2-7.5 mmol/L) voluntarily participated in an 8-wk crossover study designed to determine the effect of prunes as a source of fiber on plasma cholesterol and on fecal output and bile acid concentration. During the prune period, subjects supplemented their usual diets with 12 prunes (100 g; 6 g dietary fiber) daily. Plasma low-density-lipoprotein cholesterol was significantly lower after the prune period (3.9 mmol/L) than after the grape-juice-control period (4.1 mmol/L). Fecal bile acid concentration of lithocholic acid was significantly lower after the prune period (0.95 mg bile acid/g dry wt stool) than after the grape-juice-control period (1.20 mg bile acid/g dry wt stool). Both fecal wet and dry weights were approximately 20% higher after the prune period than after the grape-juice-control period. Total bile acids (mg/72 h) did not significantly differ between experimental periods.

Bioavailability in humans of zinc from beef: intrinsic vs extrinsic labels.

Beef is a concentrated source of zinc. However, the bioavailability of Zn from beef has not been clearly established. It is also unclear whether there is a difference in absorption between intrinsic and extrinsic Zn. To address these questions, a calf was labeled with 65ZnCl2 and the meat was used as a source of intrinsically labeled beef. Twelve subjects were given a meal containing 100 g beef labeled either intrinsically or extrinsically with 65ZnCl2. Gamma-ray emissions, as determined by whole-body counting, were used to calculate Zn absorption. Absorption values were 20.9 +/- 5.5% from the extrinsic meal and 26.4 +/- 10.6% from the intrinsic meal, a difference that was not statistically significant (p greater than 0.05). Zn absorption was thus much less than the 40% assumed in establishing the 1980 Recommended Dietary Allowance for Zn. These results also indicate that extrinsic labels of Zn are valid markers of zinc absorption in beef.

An improved procedure for bile acid extraction and purification and tissue distribution in the rat.

Two bile acid extraction procedures were compared using endogenously radiolabeled tissues and feces. The method of Setchell et al. (J. Lipid Res. 24, 1085-1100, 1983) resulted in essential complete extraction, whereas that of Manes and Schneider (J. Lipid Res. 6, 376-377, 1971) gave recoveries between 56-82%. The time requirement for the method of Setchell et al. could be drastically reduced with no loss in extraction efficiency. Using extracts from endogenously labeled material, a purification procedure using C18 solid-phase extraction cartridges was developed that recovers greater than 90% of bile acids. The distribution of bile acids within the intestinal tract and liver of the rat was determined.

Response of urinary lipophilic aldehydes and related carbonyl compounds to factors that stimulate lipid peroxidation in vivo.

Peroxidation of lipids results in the formation of a number of aldehydic and other carbonyl-containing secondary degradation products. The effect of peroxidative stimuli mediated by vitamin E deficiency, a diet high in polyunsaturated fatty acids (containing cod liver oil), and carbon tetrachloride administration on urinary excretion of a number of lipophilic aldehydes and related carbonyl compounds was examined in rats. These secondary lipid peroxidation products were measured as 2,4-dinitrophenylhydrazine derivatives. All three treatments increased urinary excretion of secondary lipid peroxidation products, although the pattern of excretion of these products varied somewhat among the treatments. Significant increases were found in butanal, hexanal, octanal, butan-2-one, pentan-2-one, hex-2-enal, hepta-2,4-dienal, 4-hydroxyhex-2-enal, 4-hydroxyoct-2-enal, 4-hydroxynon-2-enal, and a number of unidentified carbonyl compounds. These results suggest that urinary excretion of these lipophilic secondary lipid peroxidation products is a useful and noninvasive marker of whole-body lipid peroxidation.

Vitamin E and probucol reduce urinary lipophilic aldehydes and renal enlargement in streptozotocin-induced diabetic rats.

Diabetes mellitus is characterized by complications affecting several organs, including the kidney. Lipid peroxidation increases in diabetes and has been implicated in the pathogenesis of diabetic complications. In this study, we examined the ability of two antioxidants, vitamin E and probucol, to reduce lipid peroxidation in vivo and renal hypertrophy, an early stage of diabetic nephropathy, in rats. Animals were divided into four groups: non-diabetic, diabetic, diabetic treated with vitamin E, and diabetic treated with probucol. Animals were given antioxidants by intraperitoneal injection after induction of diabetes by streptozotocin injection. After 7 wk, lipid peroxidation in vivo was measured by analyzing urinary excretion of lipophilic aldehydes and related carbonyl compounds (LACC) as 2,4-dinitrophenylhydrazones by high-performance liquid chromatography. A number of urinary lipophilic nonpolar and polar aldehydes and related carbonyl compounds were identified, almost all of which increased in diabetes. Antioxidant treatment resulted in significantly decreased excretion of urinary LACC excretion. Antioxidant treatment of diabetic rats reduced renal hypertrophy. There was a high correlation between kidney weight and urinary LACC. Since LACC are accepted markers of lipid peroxidation, these results indicate that antioxidants can reduce the elevated lipid peroxidation of diabetes and may slow the onset of diabetic nephropathy.

Lipophilic aldehydes and related carbonyl compounds in rat and human urine.

Rat and human urine samples were analyzed for lipophilic aldehydes and other carbonyl products of lipid peroxidation. The following compounds were identified as their 2,4-dinitrophenyl hydrazones by cochromatography with pure standards using three solvent systems: butanal, butan-2-one, pentan-2-one, hex-2-enal, hexanal, hepta-2,4-dienal, hept-2-enal, octanal, non-2-enal, deca-2,4-dienal, 4-hydroxyhex-2-enal, and 4-hydroxynon-2-enal. In general, fasted rats excreted less of these compounds than fed rats, indicating they were partially of dietary origin or that the endogenous compounds were excreted in a form not susceptible to hydrazone formation. The compounds excreted in human urine were similar to those excreted in rat urine but were present in lower concentrations. Identification of the conjugated forms of the lipophilic aldehydes and related carbonyl compounds excreted in urine may be a source of information about their reactions in vivo.

Diabetes increases excretion of urinary malonaldehyde conjugates in rats.

The effect of streptozotocin-induced diabetes on the urinary excretion of thiobarbituric acid test-positive materials was examined. In diabetic rats, urinary excretion of thiobarbituric acid reactive substances was increased 5-fold over that in nondiabetic animals. High-performance liquid chromatography of urine samples revealed that five of the six fractions previously found to be increased in vitamin E deficiency [Lee, H.-S., Shoeman, D.W., and Csallany, A.S. (1992) Lipids 27, 124-128] were also significantly increased in streptozotocin-induced diabetes. The data suggest that a high level of oxidative stress is induced by uncontrolled diabetes in rats.

Animal models in human nutrition research.

Animal models are used extensively in nutritional research. Studies with animal models may not provide a discussion of the applicability of the model to humans, and seldom do such studies discuss the limitations of the model. This article presents information that is targeted toward the nutrition support practitioner about the use of animal models in nutritional research. The rationale for using animal models and the applicability to humans, the limitations of applicability, and the unique opportunities related to animal models is presented.

Dietary effects of distillers dried grains with solubles on performance and milk composition of lactating sows.

A study was conducted to evaluate the dietary effect of adding increasing concentrations of distillers dried grains with solubles (DDGS) to corn- and soybean meal-based sow lactation diets on sow and litter performance, energy and N digestibility, plasma urea N (PUN), and milk fat and protein concentrations. Mixed-parity sows [n = 307; 221 ± 15 kg of BW, 4.54 parities, litter size of 10.6, and litter weight at birth (alive) of 15.14 kg] were assigned randomly to 1 of 5 dietary treatments: control (CON; corn-soybean meal); 10, 20, and 30% DDGS; and 30% DDGS high-protein (HP) diets. Sows were moved to farrowing rooms on d 109 of gestation and were fed the dietary treatments until weaning. Within each treatment group, feces and urine for energy and N digestibility analysis (from d 10 to 12 of lactation) and blood for PUN analysis and milk fat and protein concentrations (on d 0 and 19 of lactation) were collected from 6 randomly chosen parity 3 to 5 sows. There were no dietary effects (P = 0.10) of DDGS on ADFI of sows and sow backfat change. However, sows fed 30% DDGS HP lost more BW compared with sows fed CON (P < 0.05). There were no dietary effects (P = 0.71) of DDGS on preweaning mortality of piglets, litter weight gain, and piglet ADG. Dietary treatments did not affect (P > 0.05) DE, ME, N retention, or N digestibility of the diets. There were no differences in the concentrations of fat and protein in milk at weaning (d 19) among dietary treatments. Sows fed 20 and 30% DDGS had less (P < 0.05) PUN at weaning (d 19) than sows fed CON and 30% DDGS HP. Inclusion of up to 30% DDGS in a lactation diet did not affect (P > 0.05) sow and litter performance, DE and ME contents of the diets, N retention and digestibility, and milk composition compared with sows fed a corn-soybean meal CON diet. It was concluded that addition of up to 30% DDGS in a lactation diet will support satisfactory sow and litter performance.

Effect of soluble and insoluble fiber on energy digestibility, nitrogen retention, and fiber digestibility of diets fed to gestating sows.

Twenty-four sows (12 nulliparous, 12 multiparous) were used to determine soluble fiber (SF) and insoluble fiber (ISF) effects on energy digestibility, N balance, and SF and ISF digestibility. Experimental diets included a corn-soybean meal control (C; 1.20% SF, 9.78% ISF), a 34% oat bran diet high in SF (HS; 3.02% SF, 10.11% ISF), a 12% wheat straw diet high in ISF (HIS; 1.11% SF, 17.86% ISF), and a 16% sugar beet pulp diet (HS + HIS; 2.32% SF, 16.08% ISF). Sows were assigned randomly to diets within parity group and individually fed to meet their energy requirements according to the NRC model assuming 10 pigs per litter and 40 kg of gestation gain. Total feces and urine were collected in 5-d periods at wk 5, 10, and 14 of gestation. There were no interactions between dietary treatments and parity group for any of the response criteria evaluated. Dietary energy digestibility was greatest (P < 0.01) for females fed C (87.9%) and HS (89.3%) diets compared with females fed diets high in ISF (HIS, 82.9; HS + HIS, 86.8%). Energy digestibility was not affected by stage of gestation. Dietary N digestibility was similar between C and HS (86.1 and 86.2%) but greater (P < 0.01) than HIS and HS + HIS (82.8 and 82.8%, respectively). Nitrogen digestibility declined (P < 0.05) as gestation progressed for sows fed HS only. Nitrogen retention as a percentage of N intake was not affected by diet (C, 51.8; HS, 44.0; HIS, 42.0; HS + HIS, 48.6). Soluble fiber digestibility was different (P < 0.01) among experimental diets (C, 85.8; HS, 89.5; HIS, 77.7; HS + HIS, 80.3%). Sows fed HS + HIS (61.8%) and HS (58.4%) had greater (P < 0.05) ISF digestibility than sows fed C (53.5%), whereas sows fed HIS (38.3%) had lower (P < 0.01) ISF digestibility than sows fed the other experimental diets. Greater digestibility of dietary energy (87.1 vs. 86.2%; P < 0.05), N (85.7 vs. 83.2%; P < 0.01), and ISF (54.5 vs. 51.2%; P < 0.06) was observed in multiparous vs. nulliparous sows. In conclusion, increased intake of ISF decreased energy digestibility, whereas increasing SF intake improved energy digestibility. Diet had no effect on N retention. Insoluble fiber digestibility improved when SF intake increased, suggesting that knowledge of specific dietary fiber components is necessary to accurately predict effects of dietary fiber on digestibility. Multiparous sows demonstrated a greater ability to digest fibrous diets than nulliparous sows.

Beef tallow, but not corn bran or soybean polysaccharide, reduces large intestinal and fecal bile acid concentrations in rats.

Diets high in fat and low in dietary fiber have been associated with a higher incidence of colon cancer, possibly by increasing bile acid concentration in the colon. Therefore changes in bile acid metabolism due to beef tallow, corn bran (CB), and soy polysaccharide (SP) feeding were studied. Rats were fed one of four diets for six weeks: 5% beef tallow fiber-free (LF), 20% beef tallow fiber-free (HF), 20% beef tallow with CB (HFCB), and 20% beef tallow with SP (HFSP). HF increased fecal output compared with LF, and HFCB and HFSP increased fecal output compared with HF. HF reduced fecal bile acid concentration by two-thirds compared with LF, although daily bile acid excretion was similar. There was a tendency toward a smaller bile acid quantity in the small intestine with HF than with LF. Neither fiber altered total fecal bile acid concentration or small intestinal bile acid quantity compared with HF. However, 7 alpha-dehydroxylase activity in the colon was lower with HFSP than with HFCB. Increasing dietary beef tallow from 5% to 20% in animals fed a fiber-free diet greatly reduced the concentration of bile acids in the large intestine and feces, an effect associated with a reduced risk of colon cancer.

The effect of synbiotics on colon carcinogenesis in rats.

Evidence indicates that consumption of probiotic microorganisms such as bifidobacteria reduces the risk of colon cancer in animal models. Feeding certain fructans such as oligofructose and inulin, which are thought to selectively increase the growth of intestinal bifidobacteria (i.e., a prebiotic effect), also has been shown to reduce colon cancer risk. The objective of our study was twofold, i. e., to determine whether the combination of bifidobacteria and oligofructose would have an additive effect (i.e., synbiotic) in reducing colon cancer risk in rats, and to determine whether other oligosaccharides would also be effective as part of a synbiotic combination. The development of colonic preneoplastic lesions (aberrant crypts) was used as an index of colon cancer risk. In one series of experiments, rats were given the carcinogen 1, 2-dimethylhydrazine (DMH) and administered one of the following treatments: skim milk (control), bifidobacteria (bifido), oligofructose (OF) or bifido + OF. Neither bifido nor OF alone significantly reduced aberrant crypt number. Bifido + OF reduced aberrant crypt number in five of six experiments, although the reduction was significant in only one. However, a paired comparison of the six experiments indicated a significant overall reduction in aberrant crypts by bifido + OF (P = 0.039). Soybean oligosaccharide (SBO) and wheat bran oligosaccharide (WBO) were also fed in combination with bifidobacteria. In two other experiments, SBO did not alter the number of aberrant crypts compared with the control, whereas WBO reduced aberrant crypt number in one experiment but not in another. Of OF, SBO and WBO, only SBO reduced the colonic mucosa proliferation compared with the control. These results suggest that the combination of bifidobacteria and oligofructose reduces colon cancer risk in carcinogen-treated rats, but the effect of other oligosaccharides is uncertain.

Effects of corn oil and wheat brans on bile acid metabolism in rats.

High concentrations of colonic bile acids may promote tumor formation. Some studies have found that high levels of dietary fat increase fecal bile acid excretion, whereas others report no effect. Wheat bran appears to reduce fecal bile acid concentration. This study was conducted to determine the effect of different dietary fat levels and types of wheat bran on bile acid metabolism. Rats were fed diets containing either no fiber, 2% cholestyramine (CHO) or brans of hard red spring, soft white winter or durum wheat--at both a 5 or 20% fat level. Animals were fed for 7 wk, and feces were collected in the last week. Wheat bran (all types) significantly increased fecal mass approximately fourfold, and CHO significantly increased fecal mass twofold compared to the fiber-free diet. Increasing the fat level did not increase fecal bile acid excretion, nor did the addition of wheat bran. Addition of CHO, however, more than doubled it. CHO increased fecal bile acid concentration, all wheat brans decreased it and fat level had no effect. Bile acid pool size was increased slightly by fat level and cholestyramine feeding but not by wheat brans. These results indicate that fat level slightly alters bile acid metabolism but that wheat brans do not.

Relationships between viscosity of hydroxypropyl methylcellulose and plasma cholesterol in hamsters.

Dietary high viscosity hydroxypropyl methylcellulose (HPMC) lowered plasma and liver cholesterol concentrations in cholesterol-fed hamsters. To determine the level of viscosity needed to effect a significant reduction in total plasma cholesterol, hamsters were fed for 3 wk diets containing 0.12% cholesterol and either 4% cellulose or one of four preparations of HPMC that varied in viscosity between 14 and 1698 centipoise (cP), as estimated in vitro. Blood was collected for plasma cholesterol determination, and intestinal contents were obtained by finger-stripping of the excised small intestine. Contents were centrifuged and the supernatant (ex vivo) viscosity determined. In vitro and ex vivo viscosities were correlated (R2 = 0.96). Plasma cholesterol concentrations declined as in vitro or ex vivo viscosity increased. Maximal plasma cholesterol reduction occurred at an ex vivo viscosity of approximately 150 cP. There was a linear relationship between plasma cholesterol and the logarithm of ex vivo viscosity (R2 = 0.98). Our results suggest that materials that increase the viscosity of intestinal contents can be effective in reducing plasma cholesterol and that only moderate increases in viscosity are necessary to achieve this effect.

Bile acid metabolism in rats fed two levels of corn oil and brans of oat, rye and barley and sugar beet fiber.

High concentrations of fecal bile acids are associated with a higher incidence of colon cancer. Dietary changes that alter bile acid metabolism are therefore of interest. Here, we report the effect of feeding diets containing four fiber sources and two fat levels for 7 wk on bile acid excretion and small intestinal bile acids (an index of pool size) in rats. The fiber sources were oat bran, rye bran, barley bran and sugar beet fiber. Fiber-containing diets were 8% dietary fiber and contained either 5 or 20% corn oil. All fiber sources caused significantly greater fecal output compared with the fiber-free basal diet. All fiber sources also resulted in significantly (P less than 0.05) lower fecal bile acid concentration compared with the fiber-free basal diet. Only rye bran resulted in significantly (P less than 0.05) higher total fecal bile acid excretion. Oat bran resulted in a slightly but significantly (P less than 0.05) higher quantity of small intestine bile acids compared with the other diets. Dietary fat level had no significant effect on fecal bile acid concentration or excretion or quantity of small intestinal bile acids. We conclude that all four fiber sources tested resulted in lower fecal bile acid concentration, by effectively causing greater fecal mass. Changes in dietary fat level as corn oil had no effect on fecal bile acids.

Dietary guar gum halts further renal enlargement in rats with established diabetes.

Guar gum, a dietary fiber known to improve glucose tolerance, was fed to rats with established diabetes to determine its effect on renal enlargement and microalbuminuria. Diabetic rats were fed a modified AIN-76A (basal) diet for 4 wk, at which time half the rats continued to receive the same basal diet (DB-BA group) and half were switched to a 5% guar gum diet (DB-GG group). Nondiabetic rats fed the basal diet served as controls (NRL group). After 8 additional weeks the animals were killed. Glycated hemoglobin, a measure of long-term blood glucose control, was 14.4% in the DB-BA group and 12.4% in the DB-GG group, a statistically significant difference (P < 0.05). Kidney weight of the DB-BA group (3.51 g) was significantly greater than that of the DB-GG group (2.76 g) (P < 0.05). Eight weeks after induction of diabetes, 24-h urinary albumin excretion was highest in the DB-BA group and lowest in the NRL group; excretion in the DB-GG group (4 wk of guar feeding) was intermediate. However, by 12 wk no differences in albumin excretion among the groups were apparent. These results suggest that guar gum may be useful for slowing the progression of diabetic nephropathy and that guar gum deserves further study in this regard.

Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters.

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.

Reduced digestibility of beef tallow and cocoa butter affects bile acid excretion and reduces hepatic esterified cholesterol in rats.

We investigated stearic acid (18:0) digestibility and how it affects bile acid excretion in male Sprague-Dawley rats fed diets containing (g 18:0/ 100 g fatty acids): pork lard (13); beef tallow (19); cocoa butter (35); corn oil (2) or corn oil plus cholestyramine for 25 d. Apparent lipid digestibility was reduced with increased dietary intake of 18:0 as follows: lard (90%), beef tallow (82%), cocoa butter (78%), cholestyramine (87%), and corn oil (94%); P < 0.001, pooled SD = 2. Hepatic concentrations of total and esterified cholesterol were significantly less in cocoa butter-, beef tallow- and cholestyramine-fed groups compared with lard- and corn oil-fed groups. Fecal bile acid excretion was significantly greater in rats fed cocoa butter or cholestyramine compared with those fed corn oil. The half-life of intraperitoneally administered 14C-cholic acid was significantly longer in rats fed cocoa butter (1.36 +/- 0.02 d) compared with cholestyramine (0.98 +/- 0.03 d) and intermediate in those fed corn oil, lard or beef tallow (1.11-1.21 +/- 0.05 d). Fecal excretion of muricholic acids (bile acids) correlated strongly with dietary intake of 18:0 (r2 = 0.98, P < 0.01), whereas excretion of bile acids derived from cholic and chenodeoxycholic acids was similar among groups. In summary, the lower digestibility of cocoa butter is associated with increased fecal bile acid excretion, reduced hepatic concentration of esterified cholesterol, decreased fractional turnover of 14C-cholic acid and increased excretion of muricholic acids in rats. The mechanism by which stearate-rich dietary fats alter bile acid and cholesterol metabolism is, however, uncertain.

The role of probiotic cultures in the prevention of colon cancer.

Risk factors for colon cancer include both hereditary and environmental factors. Dietary patterns represent controllable risk factors for the development of colon cancer. Much attention has focused on decreasing colon cancer risk through increasing intake of dietary fiber; recently, this has included interest in the consumption of prebiotics and probiotics. Because factors involved in the initiation and promotion of colon cancer might be separated in time from actual tumor development, it is difficult to choose "outcomes" or "end points" that are definitive indicators of efficacy of probiotics or prebiotics. Studies that have explored the cause-effect relationship directly have used animal models. In this review, we have confined our discussion to animal studies from the last 10 years that have examined most directly the relationship between prebiotic and probiotic consumption and colon cancer development. To present the consensus of these studies first, it appears that probiotics with or without prebiotics have an inhibitory effect on the development of aberrant crypts (precancerous lesions) and tumors in animal models. The effect is not completely consistent and is small in some studies, but this may represent a dose or time effect.