Chemopreventive effects of orange peel extract (OPE). I: OPE inhibits intestinal tumor growth in ApcMin/+ mice

Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds associated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract (OPE) on intestinal tumor growth in Apc(Min/+) mice, a mouse model for human familial adenomatous polyposis (FAP). The OPE contained 30% polymethoxyflavones, a mixture that included tangeretin (19.0%), heptamethoxyflavone (15.24%), tetramethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). Apc(Min/+) mice were fed one of four diets: (1) AIN-76A control diet; (2) a new Western-style diet (NWD), i.e., AIN-76A diet modified with decreased calcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25% OPE; and (4) NWD with 0.5% OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the Apc(Min/+) mice, tumors increased mainly in the colon, with tumor multiplicity increasing 5.3-fold and tumor volume increasing 6.7-fold. After feeding 0.5% OPE in NWD, the development of tumors markedly decreased, with multiplicity decreasing 49% in the small intestine and 38% in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5% OPE in NWD further increased apoptosis in tumors of the small and large intestine. Findings indicated that OPE inhibited tumorigenesis in this preclinical mouse model of FAP, and increased apoptosis may have contributed to this effect.     

APCmin/+小鼠缺失维生素D受体对肠道肿瘤生长的影响

目的 探讨维生素D受体(VDR)失活对APCmin/+小鼠肠道肿瘤生长的影响及机制.方法 通过构建APCmin/+VDR-/-小鼠模型(n=8),与APCmin/+小鼠比较(n=8),4月龄时观察肠道肿瘤大小及数目情况,肿瘤作HE染色以判断病理类型,免疫组化检测肿瘤相关基因BCL-2、vimentin-1、Stat-1和MSH-2蛋白的表达.结果 4月龄时2组鼠比较,APCmin/+VDR-/-小鼠>3 mm肿瘤明显增多(P<0.01).HE染色显示肠道肿瘤为管状腺瘤.APCmin/+肿瘤的Stat-1表达较强,而MSH-2和vi-mentin-1表达在APCmin/+VDR-/-肿瘤中均更强.结论 维生素D受体缺失促使APCmin/+小鼠肠道肿瘤的发展.     

APCmin/+小鼠缺失维生素D受体对肠道肿瘤生长的影响

目的 探讨维生素D受体(VDR)失活对APCmin/+小鼠肠道肿瘤生长的影响及机制.方法 通过构建APCmin/+VDR-/-小鼠模型(n=8),与APCmin/+小鼠比较(n=8),4月龄时观察肠道肿瘤大小及数目情况,肿瘤作HE染色以判断病理类型,免疫组化检测肿瘤相关基因BCL-2、vimentin-1、Stat-1和MSH-2蛋白的表达.结果 4月龄时2组鼠比较,APCmin/+VDR-/-小鼠>3 mm肿瘤明显增多(P<0.01).HE染色显示肠道肿瘤为管状腺瘤.APCmin/+肿瘤的Stat-1表达较强,而MSH-2和vi-mentin-1表达在APCmin/+VDR-/-肿瘤中均更强.结论 维生素D受体缺失促使APCmin/+小鼠肠道肿瘤的发展.     

Age-related changes in sucrase and lactase activity in the small intestine of 3- and 10-week-old obese mice (C57BL/6Jobob)

The relationship between obesity and the digestion of carbohydrates is poorly understood. Data in humans have provided conflicting results. Studies using the obese mouse (C57BL/6Jobob) suggest that obesity is associated with increased activity of intestinal alpha-disaccharidases. To evaluate the developmental pattern of these enzyme activities in obesity, we determined the activity of sucrase and lactase in the small intestine of genetically obese mice (C57BL/6Jobob) and lean littermates at 3 and 10 weeks of age. Sucrase and lactase activities were measured on intestinal homogenates from segments of the small intestine in mice maintained on standard laboratory diets during the postweaning period. Results were expressed as specific activity and total activity per intestinal segment. Obese mice did not differ from lean littermates in body weight at 3 weeks of age, but exhibited increased protein content in the proximal small intestine. Sucrase specific activity was significantly higher in the obese mice at 3 weeks of age in all intestinal segments. Sucrase total activity showed a similar pattern. At 10 weeks of age, body weights of obese mice were substantially greater than the lean littermates. Sucrase specific and total activities were also greater in the obese mice at 10 weeks of age. Lactase specific activity, however, was similar in both obese and lean mice at both ages studied. Lactase total activity was greater in the obese mice, consistent with their greater intestinal mass. These observations demonstrate that changes in the intestinal sucrase activity of the obese mouse precede the development of excessive body weight.     

Adiposity-related protection of intestinal tumorigenesis: interaction with dietary calcium

Although high-calcium diets have been reported to reduce the risk of colorectal cancer, our preliminary data with the adenomatous polyposis coli (Apc) Min mutation (Min/+;Apc(Min/+)) mouse shows a paradoxical increase in intestinal tumor loads (> 65%) with high calcium diets. Since we previously demonstrated that increasing dietary calcium reduces adiposity, and Apc(Min/+) mice on high calcium diets exhibited profound loss of adipose tissue, we hypothesized that loss of an adipose tissue-derived tumor suppressor factor(s) resulted in increased tumor susceptibility in animals on the high calcium diet. Accordingly, tumor prone Apc(Min/+) mice were crossed with obesity prone lethal yellow agouti (A(y)/a) mice to generate obese A(y)/Apc(Min/+) mice. Low (0.2%), normal (0.5%), and high (1.2%) calcium diets were fed to both A(y)/Apc(Min/+) mice and Apc(Min/+) mice from 35-40 days until 90 days of age (n=21/strain, n=7/diet group). The high calcium diet reduced weight gain in both strains (P < 0.01) and reduced fat pad mass by 46-57% in A(y)/Apc(Min/+)(P < 0.004) and by 65-82% in Apc(Min/+)(P < 0.03).Apc(Min/+) mice on the high calcium diet exhibited an increase in tumor number (76 vs. 29, P=0.009), but this effect was not seen in the A(y)/Apc(Min/+) mice. beta-Catenin and cyclin D1 gene expression were significantly induced with high calcium diet in intestinal tumor tissue of Apc(Min/+) mice but not in A(y)/Apc(Min/+) mice. We conclude that the differential effect of dietary calcium on intestinal tumorigenesis in lean vs. obese Apc(Min/+) may result from the loss of adipose-derived protective factor(s) due to the substantial loss of body fat in Apc(Min/+) mice fed a high calcium dairy diet, increasing beta-catenin and cyclin D1 in tumors.     

Selenium-enriched broccoli decreases intestinal tumorigenesis in multiple intestinal neoplasia mice

Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer susceptibility. This study investigated whether selenium-enriched broccoli would be protective against intestinal cancer susceptibility in Min mice. Five-week-old heterozygotic male Min mice were fed an AIN-93-based diet containing either low-selenium broccoli or an equivalent amount of high-selenium broccoli for 10 wk. Mice fed the selenium-enriched broccoli had fewer (P < 0.02) small intestinal (46.4 +/- 3.7 vs. 65.6 +/- 6.1) and large intestinal (0.43 +/- 0.17 vs. 1.93 +/- 0.27) tumors than those fed an equivalent amount of unenriched broccoli. Min mice fed the selenium-enriched broccoli had small but significant (P < 0.0001) increases in plasma and liver selenium concentrations and red blood cell glutathione peroxidase activity. These results extend previous observations that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats.     

Improvement of intestinal stem cells and barrier function via energy restriction in middle-aged C57BL/6 mice

This study aimed to reveal the impact of energy restriction on the intestine via structural and molecular changes in terms of intestinal stem cell (ISC) function, ISC niche, intestinal epithelial barrier function, and intestinal immune function. Female C57BL/6J mice, aged 12 months, fed a commercial chow were used in this study. The ISC function, ISC niche, intestinal epithelial barrier function, and intestinal immune function were assessed. Energy restriction reversed aging-induced intestinal shortening and made the crypts shallower. The intestinal epithelial cells isolated from the intestine showed a significant increase in the expression levels of stem cell–associated genes in small intestinal epithelial cells as detected by flow cytometry. Despite the increase in the number of stem cells and the expression levels of markers, no increase or decrease was found in the enteroid complexity of the small intestine and colonic enteroid formation in vitro. The colonic mucous layer was measured in mice of the energy restricted (ER)–treated group to investigate the epithelial barrier function in the colon. The results revealed that the barrier was more complete. The fluorescence intensity of tight junction markers claudin-2 and zonula occludens-1 increased and the mRNA expression profiles of monocyte chemotactic protein 1 and interleukin-6 decreased in the colon of mice in the ER-treated group. The beneficial effects of ER on the colon in terms of the integrity of the mucosal barrier and alleviation of inflammation were confirmed, thus highlighting the importance of modulating the intestinal function in developing effective antiaging dietary interventions.     

High dietary niacin may increase prostaglandin formation but does not increase tumor formation in ApcMin/+ mice

High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D(2) (PGD(2)). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD(2), niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E(2) (PGE(2)) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8-3.9). PGE(2) promotes tumors in the intestines, whereas PGD(2) may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc(Min/+) mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc(Min/+) mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc(Min/+) mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.     

Quercetin's effects on intestinal polyp multiplicity and macrophage number in the Apc(Min/+) mouse

Numerous in vitro studies argue for quercetin's chemopreventive potential in colon cancer; however, experimental studies in rodents are limited. Macrophages play a role in tumorigenesis, but the effects of quercetin on macrophage infiltration in colon cancer is unknown. We examined the effects of quercetin on intestinal polyp multiplicity and macrophage number in Apc(Min/+) mice. Apc(Min/+) mice were assigned to placebo or quercetin (n = 8/group) groups. Mice were given a placebo or quercetin (0.02%) diet from 4-20 wk of age, after which intestines were analyzed for polyp number and size in the small intestine (Sections 1-4) and colon (Section 5) and for macrophage number in the small intestine (Sections 1 and 3). Spleen weight was determined as a marker of systemic inflammation. Quercetin decreased total intestinal polyps by 67% (P < 0.05). Specifically, quercetin reduced intestinal polyps in categories >2 mm (69%) and 1-2 mm (79%; P < 0.05), and in Sections 2 (75%), 3 (80%), and 4 (79%; P < 0.05). Quercetin also decreased macrophage number in Sections 1 (57%) and 3 (81%), and spleen weight (P < 0.05). These data suggest that quercetin can reduce polyp number and size distribution in the Apc(Min/+) mouse and that these effects may be related to a reduction in macrophage infiltration.     

Consumption of raw potato starch alters intestinal function and colonic cell proliferation in the rat

Raw potato starch (RPS) may escape complete digestion to enter the colon and produce alterations in colonic function, while cooked potato starch (CPS) is nearly completely digested in the rat small intestine. Effects of RPS and CPS on colonic function [fecal weight, transmit time and thymidine kinase (TK) activity (a marker for cell proliferation)] were contrasted in a 6-wk feeding study. Male F344 rats consumed either dextrose/sucrose (DS; control), 30% CPS or 30% RPS diet. RPS feeding resulted in a 3-fold increase in fecal weight and a 30% prolongation in transit time, as well as elevated levels of colonic mucosal total protein (50%) and TK activity (4- to 7-fold) compared to DS-fed rats. A second study revealed normal large intestinal histology in rats fed CPS or RPS, with elongated colonic crypts (33% increased over CPS) in group RPS. Large intestinal contents were heavier in group RPS than in group CPS. These studies demonstrate that RPS feeding significantly enhances fecal weight yet prolongs total gastrointestinal transit time. Enhanced colonic TK and elongated colonic crypts suggest that RPS stimulates colonic mucosal growth.     

Resistant carbohydrates stimulate cell proliferation and crypt fission in wild-type mice and in the Apc(Min/+) mouse model of intestinal cancer, association with enhanced polyp development

Fermentation of carbohydrates in the colon can stimulate cell proliferation and could thus be a cancer risk. The effects of resistant carbohydrates, i.e. those not digested and absorbed in the small intestine, on cell proliferation, crypt fission and polyp development were investigated in wild-type and adenomatous polyposis coli multiple intestinal neoplasia (Apc(Min/+)) mice. Fifteen 4-week-old female wild-type and fifteen Apc(Min/+) mice were used for each group and fed a chow diet, a semi-synthetic diet or the semi-synthetic supplemented with wheat bran or an apple pomace preparation, both high in resistant carbohydrates, for 8 weeks. Tissue from all mice was used to measure cell proliferation and crypt fission and tissue from the Apc(Min/+) mice was scored for polyp number and tumour burden. There were slight reductions in intestinal mass in the mice fed the semi-synthetic diets and this was increased by the inclusion of resistant carbohydrates. The Apc(Min/+) mice had elevated cell proliferation and crypt fission in the distal small intestine and colon and these were increased by the resistant carbohydrates. Bran or apple pomace significantly increased polyp number in the proximal third of the small intestine. Apple pulp more than doubled polyp number throughout the small bowel (99.2 (SEM 11.1) v. 40.0 (SEM 8.2), P<0.004). Bran and apple pomace increased polyp diameter and hence burden in the colon by 243 and 150 %, respectively (P<0.05). In conclusion, both types of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission.     

No effect on adenoma formation in Min mice after moderate amount of flaxseed

Summary Background & aim The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis. Design Male and female Min mice were fed either with a non–fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild–type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild–type mice. Results The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 ± 124.5 nmol/g vs. females 22.8 ± 16.0 nmol/g, P = 0.048) and caecum (47.6 ± 31.6 nmol/g vs. females 14.5 ± 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild–type mice (P < 0.05). Mean plasma ENL increased 7–fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon. Conclusion The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.     

Split-dose effect of X-irradiation on the induction of cell death in the fetal mouse brain

Pregnant mice were exposed to whole-body X-irradiation at a total dose of 0.25 Gy split into two 0.125 Gy exposures at 0.5-, 2- or 6-hour interval on day 13 of pregnancy. Fetuses were obtained from dams at various post-exposure periods and their brains were processed for microscopy. Undifferentiated neural cells in the ventricular zone of telencephalon (ventricular cells) were examined, and incidence of cells involved in pyknosis was evaluated. The curves of incidence of pyknotic cells plotted against time after the exposures to two split-doses at 0.5-hour and 2-hour intervals overlapped that of a single 0.25 Gy exposure; they had a common peak at 8-10 hours after the first exposure. Following two 0.125 Gy exposures at 6-hour interval, two peaks with similar elevations from background levels appeared at 6 and 12 hours after the first exposure. These results indicated that low-dose X-irradiation shows simply additive effects of split doses on cell death, without induction of adaptive response of ventricular cells of the telencephalon at day 13 of pregnancy in mice.     

Diet and age affect intestinal morphology and large bowel fermentative end-product concentrations in senior and young adult dogs

The objective of this study was to determine the effects of age and diet on intestinal morphology and large bowel fermentative end-product concentrations in healthy dogs. Small intestinal villus width, height, and area, and small intestinal and colonic crypt depth were measured. Large bowel digesta samples were analyzed for ammonia, SCFAs, and branched-chain fatty acids (BCFAs). SCFAs are considered to be beneficial fermentative end-products in the intestine because they exert trophic effects on intestinal cells. Twelve senior (age = 11.1 y +/- 0.6 at baseline; 6 male, 6 female) and 12 young adult (age = 8 wk old at baseline; 6 male, 6 female) beagles were randomly assigned to 1 of 2 dietary treatments, an animal product-based diet (APB) and a plant product-based diet (PPB). Diets were fed for 12 mo. Jejunal (P = 0.03) and ileal (P = 0.02) villus height, and duodenal (P = 0.04) villus width were greater for dogs consuming the PPB diet. Young dogs had greater (P = 0.04) jejunal villus height, whereas senior dogs had greater (P < 0.001) colonic crypt depth. Ammonia concentrations decreased (P = 0.03) from proximal to distal colon and were higher in dogs consuming APB (P = 0.03). Age and treatment affected butyrate concentrations, with senior dogs (P = 0.04) and dogs consuming APB (P = 0.04) having higher concentrations. Both diet and age affected small and large intestinal morphology, and colonic fermentative end-product concentrations in dogs.     

Adiposity-Related Protection of Intestinal Tumorigenesis: Interaction With Dietary Calcium

Although high-calcium diets have been reported to reduce the risk of colorectal cancer, our preliminary data with the adenomatous polyposis coli (Apc) Min mutation (Min/+;Apc^Min/+) mouse shows a paradoxical increase in intestinal tumor loads (> 65%) with high calcium diets. Since we previously demonstrated that increasing dietary calcium reduces adiposity, and Apc^Min/+ mice on high calcium diets exhibited profound loss of adipose tissue, we hypothesized that loss of an adipose tissue-derived tumor suppressor factor(s) resulted in increased tumor susceptibility in animals on the high calcium diet. Accordingly, tumor prone Apc^Min/+ mice were crossed with obesity prone lethal yellow agouti (A ^y /a) mice to generate obese A^y/Apc^Min/+ mice. Low (0.2%), normal (0.5%), and high (1.2%) calcium diets were fed to both A^y/Apc ^Min/+ mice and Apc^Min/+ mice from 35–40 days until 90 days of age (n = 21/strain, n = 7/diet group). The high calcium diet reduced weight gain in both strains (P < 0.01) and reduced fat pad mass by 46–57% in A ^y /Apc^Min/+(P < 0.004) and by 65–82% in Apc^Min/+(P < 0.03).Apc^Min/+ mice on the high calcium diet exhibited an increase in tumor number (76 vs. 29, P = 0.009), but this effect was not seen in the A^y/Apc^Min/+ mice.β-Catenin and cyclin D1 gene expression were significantly induced with high calcium diet in intestinal tumor tissue of Apc^Min/+ mice but not in A^y/Apc^Min/+ mice. We conclude that the differential effect of dietary calcium on intestinal tumorigenesis in lean vs. obese Apc^Min/+ may result from the loss of adipose-derived protective factor(s) due to the substantial loss of body fat in Apc^Min/+ mice fed a high calcium dairy diet, increasingβ-catenin and cyclin D1 in tumors.     

High Dietary Niacin May Increase Prostaglandin Formation but Does Not Increase Tumor Formation in Apc Min/+ Mice

High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D₂ (PGD₂). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD₂, niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E₂ (PGE₂) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8–3.9). PGE₂ promotes tumors in the intestines, whereas PGD₂ may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc ^Min/+ mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc ^Min/+ mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc ^Min/+ mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.     

Preterm birth affects the intestinal response to parenteral and enteral nutrition in newborn pigs

Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We investigated whether preterm birth alters the GI responses to parenteral and enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow's milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired intestinal immunoglobulin G uptake from colostrum, and altered relative weights of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For both ages at delivery, increases occurred in pancreatic weight (30-75%) and amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN pigs (P < 0.05). Six days of TPN feeding was associated with reduced intestinal weight for both delivery groups (60% of values in ENT, P < 0.001), but only in term TPN pigs was the weight lower than at birth (-20%, P < 0.05). Likewise, it was only in term TPN pigs that intestinal maltase activity increased, compared with ENT, and the absorption of glucose and proline decreased. Only in preterm pigs did TPN feeding increase lactase activity (+50% compared with ENT, P < 0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and sodium-coupled glucose transporter 1 (SGLT-1) were increased in TPN, compared with ENT. In conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI tract is also present after preterm birth, but the postnatal maturation of many GI functions is modified, compared with term birth. The effects of nutritional regimen on the maturation of the gut epithelium in neonates depend on gestational age at birth.     

Preterm birth affects the intestinal response to parenteral and enteral nutrition in newborn pigs

Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We investigated whether preterm birth alters the GI responses to parenteral and enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow's milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired intestinal immunoglobulin G uptake from colostrum, and altered relative weights of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For both ages at delivery, increases occurred in pancreatic weight (30-75%) and amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN pigs (P < 0.05). Six days of TPN feeding was associated with reduced intestinal weight for both delivery groups (60% of values in ENT, P < 0.001), but only in term TPN pigs was the weight lower than at birth (-20%, P < 0.05). Likewise, it was only in term TPN pigs that intestinal maltase activity increased, compared with ENT, and the absorption of glucose and proline decreased. Only in preterm pigs did TPN feeding increase lactase activity (+50% compared with ENT, P < 0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and sodium-coupled glucose transporter 1 were increased in TPN, compared with ENT. In conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI tract is also present after preterm birth, but the postnatal maturation of many GI functions is modified, compared with term birth. The effects of nutritional regimen on the maturation of the gut epithelium in neonates depend on gestational age at birth.