Effects of alanyl-glutamine on intestinal adaptation and bacterial translocation in rats after 60% intestinal resection

The effects of alanyl-glutamine dipeptide (Ala-Gln)-enriched parenteral nutrition on intestinal mucosa and gut barrier function were investigated. Wistar rats were studied. After moderate surgical stress was induced by 60% resection of the small intestine, the rats were randomized to three groups: the chow group was given standard rat chow; the PN group received standard parenteral nutrition (PN); and the Ala-Gln group received glutamine dipeptide-enriched parenteral nutrition (3% Ala-Gln). Rats were maintained on their respective diets for 8 days. The chow and Ala-Gln groups maintained serum glutamine concentrations, intestinal mucosal thickness and villus height. Bacterial translocation rates in the chow and Ala-Gln groups were 20%, which was significantly less than that in the PN group (70%, P < 0.05). The results indicated that Ala-Gln-enriched parenteral nutrition maintains intestinal adaptation and gut barrier function after massive intestinal resection and parenteral nutrition.     

谷氨酰胺对短肠综合征大鼠残留小肠、结肠形态的影响

目的：观察谷氨酰胺（Gln)对短肠综合征大鼠残留小肠、结肠形态的影响。方法：23只雄性SD大鼠切除80%小肠,随机分为三组：饮食组（n=8)大鼠术后自由进食;全胃肠外营养（TPN）组（n=8)输TPN标准液;Gln组（n=7）输TPN Gln液;正常大鼠8只,作为正常对照组。术后第7天,称体重,取残留空肠、回肠、结肠进行组织学检查（包括光镜和电镜）。结果：饮食组和Gln组术前体重无明显差异,但术后体重有明显差异;饮食组空肠粘膜绒毛高度（VH）和粘膜厚度（MT）、回肠粘膜的VH均明显大于正常组;TPN组空肠粘膜VH、MT明显小于正常组;回肠粘膜隐窝浓度（CD）、MT亦明显小于正常组;Gln组空肠和回肠粘膜VH、CD和MT明显大于TPN组;饮食组结肠MT明显大于正常组,Gln组结肠MT明显大于TPN组。结论：80%小肠切除后,残留小肠发生代偿性改变,食物刺激是残留小肠代偿的重要因素;但这种代偿不完全,TPN可维持机体体重,但可引起残留小肠粘膜萎缩;Gln能阻止TPN引起残留小肠粘膜萎缩,促进残留小肠代偿;同时Gln还促结肠粘膜增生。     

Effects of continuous enteral L-arginine in a rat model of the short bowel syndrome

The objective of this study was to evaluate whether continuous enteral supplementation of L-arginine can stimulate intestinal adaptation in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were randomly divided into three groups of 10 each: Sham rats underwent bowel transaction and received continuous enteral nutrition (Control group, Con group), SBS rats underwent 75% small bowel resection and received continuous enteral nutrition (SB group), and SBS rats underwent 75% bowel resection and received continuous enteral nutrition supplemented with L-arginine (300 mg/Kg/d) (SB-Arg group). Fat absorbability, plasma free fatty acids, parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15 after operation. After massive small bowel resection, rats had significant bowel adaptation. Compared with SB untreated rats, SB rats supplemented with L-arginine demonstrated a significant increase in fat absorbability, plasma level of free fatty acids, ileal mucosal weight and DNA content, jejunal and ileal mucosal protein content, jejunal and ileal villus length, crypt depth and mucosal thickness. L-arginine supplementation increased enterocyte proliferation, while decreasing enterocyte apoptosis. We suggest that after massive small bowel resection, continuous enteral supplementation of L-arginine can stimulate intestinal adaptation. L-arginine may be a trophic factor to stimulate intestinal adaptation in rats of SBS.     

Biochemical and morphological changes in the digestive tract of rats after prenatal and postnatal malnutrition

Six-week-old rats subjected to prenatal and postnatal dietary restriction (maternal and weanling intake = 50% that of controls) were studied. Compared with controls, malnourished rats not only had reduced body (78 +/- 12 vs 187 +/- 21 g) and organ weights (small intestine: 4.51 +/- 0.46 vs 9.89 +/- 0.61 g; colon: 0.75 +/- 0.08 vs 1.77 +/- 0.18 g; liver: 2.75 +/- 0.34 vs 9.13 +/- 1.33 g; pancreas: 0.78 +/- 0.14 vs 1.67 +/- 0.49 g) but also decreased body weight-length ratios (6.5 +/- 0.3 vs 10.8 +/- 1.4 g/cm) and serum albumin levels. The small intestinal mucosa was hypotrophic (protein-DNA ratio: 5.02 +/- 1.43 vs 8.82 +/- 0.68, malnourished vs controls, respectively) with reduced mucosal thickness, villus height, and crypt depth. Specific activities of lactase, maltase, and sucrase were diminished (53%, 66%, 54% of control values, respectively). Colonic mucosa was hypoplastic with decreased mucosal thickness and crypt depth. Liver and pancreas were both hypotrophic and hypoplastic. The findings suggest that, in contrast to colonic mucosa, pancreas, and liver, the small intestinal mucosa maintained cell number during prolonged prenatal and postnatal malnutrition.     

添加rhGH与Gln的肠外营养对短肠大鼠小肠代偿作用的研究

目的研究添加生长激素(rhGH)及谷氨酰胺(Gln)的肠外营养(PN),对短肠大鼠残存小肠代偿的作用及作用机制。     

大鼠短肠综合征全肠外营养模型的建立

目的通过切除大鼠中段小肠,建立大鼠短肠综合征(SBS)全肠外营养模型(PN)。方法选择清洁级Wistar雄性大鼠30只,随机分为20种氨基酸组(Gln-PN组)、17种氨基酸组(Std-PN组)、无氮组。三组动物均切除75%的小肠,空肠近端及回肠末端各保留10cm,空回肠以5-0丝线对端吻合。从其右侧颈外静脉插管并持续输注含有不同结晶氨基酸的肠外营养液,同时观察术后动物表现及各组动物间体重、氮平衡、肠粘膜的形态结构和免疫学指标的变化。结果该动物模型基本符合短肠综合征的临床表现,不同组动物间体重、氮平衡、肠粘膜的形态结构及外周血CD4 /CD8 差别显著(P<0.05)。结论本模型在研究不同营养成分对SBS大鼠营养支持效果、SBS大鼠肠粘膜病理形态改变及临床愈后等方面可供临床选用,且其重复性好、稳定、动物活动不受限、存活率高,具有一定的应用价值。     

Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome

BACKGROUND: Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation. OBJECTIVE: Our objective was to determine whether supplemental enteral nutrients (SEN) modulate the intestinotrophic response to a low dose of GLP-2 coinfused with PN in a rat model of SBS (60% jejunoileal resection plus cecectomy). DESIGN: Rats were randomly assigned to 8 treatments by using a 2 x 2 x 2 factorial design and maintained with either TPN or PN for 7 d. The 3 main treatment effects were the following: transection or resection (TPN alone), +/- SEN (days 4-6), and +/- GLP-2 (100 mug . kg body wt(-1) . d(-1)). RESULTS: The treatments induced differential growth of duodenal and jejunal mucosa. Significant differences in villus height, crypt depth, dry mass, and concentrations of protein and DNA were observed between the treatments and TPN alone (SEN: 15-59% increase; GLP-2: 14-84% increase; and SEN + GLP-2: 63-160% increase). Plasma concentrations of bioactive GLP-2 were significantly greater with GLP-2 infusion (TPN alone: 25 +/- 9 pmol/L; SEN: 29 +/- 10 pmol/L; GLP-2: 59 +/- 31 pmol/L; SEN + GLP-2: 246 +/- 40 pmol/L) and correlated with mucosal growth. Jejunal sucrase activity (in U/cm) was significantly greater with SEN than without SEN. SEN + GLP-2 induced dramatic mucosal growth and greater plasma concentration of GLP-2 (SEN x GLP-2 interaction, P < 0.0001). Resection significantly increased expression of proglucagon mRNA in colon. CONCLUSIONS: Combination treatment with SEN and GLP-2 induced a synergistic response resulting in greater mucosal cellularity and digestive capacity in parenterally fed rats with SBS. This shows that SEN improve the intestinotrophic response to exogenous GLP-2, possibly by stimulating enterocyte proliferation and differentiation.     

Parenteral but Not Enteral Omega‐3 Fatty Acids (Omegaven) Modulate Intestinal Regrowth After Massive Small Bowel Resection in Rats

Background: The purpose of the present study was to evaluate the effects of ω‐3 fatty acids (Omegaven) on early intestinal adaptation in rats with short bowel syndrome (SBS). Methods: Male Sprague‐Dawley rats were randomly assigned to 1 of 4 groups: sham rats underwent bowel transection; SBS rats underwent 75% bowel resection; SBS‐O ω‐3 rats underwent bowel resection and were treated with oral Omegaven given by gavage; and SBS‐I ω‐3 rats underwent bowel resection and were treated with Omegaven given intraperitoneally. Rats were killed on day 14. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depths, cell proliferation and apoptosis) were determined at time of death. Real‐time polymerase chain reaction was used to determine the level of Bax and Bcl‐2 messenger RNA (mRNA). Statistical analysis was performed using Kruskal‐Wallis test followed by post hoc test, with P < .05 considered statistically significant. Results: Oral ω‐3 supplementation did not significantly change intestinal regrowth. In contrast, parenteral ω‐3 in rats that underwent resection resulted in higher bowel and mucosal weights, mucosal DNA and protein in ileum, villus height in ileum, crypt depth in jejunum and ileum, and greater rates of cell proliferation in jejunum and ileum compared with SBS animals. The initial decreased levels of apoptosis corresponded with the early decrease in Bax and increase in Bcl‐2 mRNA levels. Conclusions: Parenteral but not enteral Omegaven augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased apoptosis reflect increased cell turnover in Omegaven‐treated animals.     

Enteral feeding preserves gut Th-2 cytokines despite mucosal cellular adhesion molecule-1 blockade

BACKGROUND: Parenteral nutrition (PN) decreases gut-associated lymphoid tissue (GALT), the intestinal IgA stimulating cytokines IL-4 and IL-10 in gut homogenates, intestinal IgA levels and the expression of Peyer patch (PP) mucosal cellular adhesion molecule-1 (MAdCAM-1), an adhesion molecule found on the high endothelial venules of PP and other tissues. IL-4 in PP stimulates MAdCAM expression in vitro. MAdCAM-1 blockade with MECA-367 reduces GALT cell populations to PN levels but maintains intestinal IgA levels if the animals are chow fed. This study compares IL-4 levels in PP of chow and PN fed mice and measures the effects of MAdCAM blockade on IL-4 and IL-10 levels in gut homogenates of chow fed mice. We hypothesized that in vivo IL-4 levels drop in PP of PN fed mice and IL-4 and IL-10 levels are maintained after MAdCAM-1 blockade in chow fed mice. METHODS: Exp 1: 18 mice received chow or PN for 5 days to determine PP IL-4 levels. Exp 2: 44 mice were randomized to chow + control monoclonal antibody (mAb), chow + MECA-367 (anti-MAdCAM-1 mAb) or PN for 4 days before measurement of IL-4 and IL-10 levels in gut homogenates. RESULTS: Exp 1: IL-4 levels in vivo were lower in PP of PN-fed mice than chow fed mice (92.0 +/- 15.1 pg/mL vs 251.1 +/- 14.8, p = .0003). Exp 2: IL-4 levels were significantly higher in chow + control mAb (187.1 +/- 44.1 pg/mL) and chow + MECA-367 (110.9 +/- 19.1 pg/mL) groups than PN mice (21.8 +/- 30.6 pg/mL, p < .02 vs chow + control or chow + MECA-367). IL-10 levels were significantly lower with PN (23.1 +/- 40.9 pg/mL) with chow+control (174.0 +/- 22.2 pg/mL p < .01), or chow + MECA-367 (181.7 +/- 23.1 pg/mL, p < .02 vs PN). CONCLUSIONS: PN-feeding reduces in vivo IL-4 levels in PP (consistent with lowered MAdCAM-1 expression) and IL-4 and IL-10 levels in gut homogenates compared with chow. Despite MAdCAM-1 blockade, enteral feeding preserved gut IL-4 levels and increased IL-10 levels consistent with preserved IgA levels.     

Malnutrition impairs postresection intestinal adaptation

BACKGROUND: Postresection intestinal adaptation is influenced by several factors, including luminal nutrients. Adaptation is impaired in the absence of luminal nutrients, even if the nutrition is maintained via total parenteral nutrition (TPN). Reduced enteral intake also inhibits adaptation if malnutrition is present, but the mechanism has not been completely defined. Our aim was to study the effect of reduced enteral nutrition on adaptation and enterocyte production and death after 50% proximal resection in rats. METHODS: Eighteen Lewis rats underwent either transection (n =6) or 50% proximal resection (n =12). The resected animals either ate ad libitum (n = 6) or were offered 75% of ad libitum intake (n =6). Nutritional status and intestinal adaptation were determined 14 days after surgery. RESULTS: Resected animals receiving 75% normal intake had decreased body weight (89% +/- 4% vs 112% +/- 2% and 112% +/- 1%, p < .05) and serum albumin (2.7 +/- 0.1 vs 3.2 +/- 0.0 g/dL and 3.0 +/- 0.1 g/dL, p < .05) compared with resection with normal intake and transection, respectively. Intestinal weight (0.32 +/- 03 vs 0.22 +/- 0.02 g/cm and 0.19 +/- 0.03 g/cm, p < .05) and diameter (10.5 +/- 0.5 vs 8.5 +/- 1.0 mm and 7.8 +/- 0.8 mm, p < .05) increased after resection alone compared with transection and malnourished resection groups. Gut weight and diameter and villus height were lower in malnourished resected animals than with transection. Crypt cell production rate was significantly lower in the reduced intake animals. Apoptosis was increased in both crypt and villus enterocytes in normally nourished but not malnourished resected animals. Villus apoptosis correlated with villus height. CONCLUSIONS: Intestinal adaptation is impaired by a 25% reduction in enteral nutrients, confirming that both the route and quantity of nutrient intake are important in this process. Both enterocyte production and loss via apoptosis are decreased by reduced enteral intake and malnutrition after resection. The correlation between villus height and apoptosis suggests that the reduced apoptosis reflects the smaller enterocyte number in malnourished animals rather than an adaptive response to maintain intestinal structure.     

Effects of adding butyric acid to PN on gut-associated lymphoid tissue and mucosal immunoglobulin A levels

Background: Parenteral nutrition (PN) causes intestinal mucosal atrophy, gut‐associated lymphoid tissue (GALT) atrophy and dysfunction, leading to impaired mucosal immunity and increased susceptibility to infectious complications. Therefore, new PN formulations are needed to maintain mucosal immunity. Short‐chain fatty acids have been demonstrated to exert beneficial effects on the intestinal mucosa. We examined the effects of adding butyric acid to PN on GALT lymphocyte numbers, phenotypes, mucosal immunoglobulin A (IgA) levels, and intestinal morphology in mice. Methods: Male Institute of Cancer Research mice (n = 103) were randomized to receive either standard PN (S‐PN), butyric acid–supplemented PN (Bu‐PN), or ad libitum chow (control) groups. The mice were fed these respective diets for 5 days. In experiment 1, cells were isolated from Peyer's patches (PPs) to determine lymphocyte numbers and phenotypes (αβTCR⁺, γδTCR⁺, CD4⁺, CD8⁺, B220⁺ cells). IgA levels in small intestinal washings were also measured. In experiment 2, IgA levels in respiratory tract (bronchoalveolar and nasal) washings were measured. In experiment 3, small intestinal morphology was evaluated. Results: Lymphocyte yields from PPs and small intestinal, bronchoalveolar, and nasal washing IgA levels were all significantly lower in the S‐PN group than in the control group. Bu‐PN moderately, but significantly, restored PP lymphocyte numbers, as well as intestinal and bronchoalveolar IgA levels, as compared with S‐PN. Villous height and crypt depth in the small intestine were significantly decreased in the S‐PN group vs the control group, however Bu‐PN restored intestinal morphology. Conclusions: A new PN formula containing butyric acid is feasible and would ameliorate PN‐induced impairment of mucosal immunity.     

Effects of oral supplementation of glutamine on small intestinal mucosal mass following resection.

Following massive small bowel resection, the remaining small bowel increases in mucosal weight, protein, deoxyribonucleic acid (DNA) content and absorptive function. Enteral nutrients are known to be important in stimulating this response. Recently, glutamine has been described as an essential fuel for the small intestinal mucosa and is thought to be trophic to the small bowel. We investigated if glutamine, when added to the diet in large quantities, might stimulate mucosal adaptation beyond that which normally occurs following physiologic feedings. Male Sprague-Dawley rats were placed on powdered rat chow supplemented with either 5% glutamine, 5% glycine or 5% glucose. After 4 days rats underwent 70% jejunoileal resection. Fourteen days after resection, protein, DNA and sucrase activity in the duodenum of the glutaminefed animals were all significantly lower than results from both the glycine and glucose groups. Duodenal mucosal weight was lower in the glutamine group than in the glycine group. In the ileum, DNA content was significantly lower for the glutamine group than the glycine group. These results suggest that high concentrations of glutamine in the diet can have negative effects on intestinal adaptation.     

Bolus ornithine and arginine-ketoglutarate supplementation in distal intestine after 65% resection in rats

Introduction: Enteral feeding has been reported to increase intestinal mucosa proliferation after resection. Dietary components influence the intestinal adaptive response. The purpose of this study was to evaluate the effect of ornithine- (OKG) or arginine-ketoglutarate (AKG) bolus supplementation on intestinal postresectional adaptation in the rat. Methods: Male Wistar rats underwent 65% small-bowel resection and received either OKG 3 g/kg/day, isonitrogenous AKG or saline by gavage once daily. The animals had free access to rat chow. Sampling was done 10 days after resection. Fed animals without surgery or specific treatment served as controls. Results: Mucosal wet weight, DNA, RNA, protein content and sucrose activity of the mucosa, as well as villus height were significantly increased in all resected animals compared to controls. No significant differences in body weight or intestinal adaptation could be found between the three dietary groups. Conclusion: Postoperative enteral bolus feeding supplemented with OKG or AKG did not significantly enhance the adaptation of the remnant small bowel 10 days after massive intestinal resection when rats had free access to rat chow.     

Oral ornithine a-ketoglutarate accelerates healing of the small intestine and reduces bacterial translocation after abdominal radiation

The effect of dietary ornithine a-ketoglutarate (OKG) on intestinal mucosal integrity and bacterial translocation was studied in rats following administration of a single dose of abdominal radiation (1100 cGy). Following the radiation injury the rats were randomized to receive a nutritionally incomplete diet which contained only water and OKG or a control diet with water and the non-essential amino-acid glycine. Four days after radiation, rats were anaesthetized and a laparotomy was performed. Cultures from mesenteric lymph nodes were taken and two tissue samples from the terminal ileum were also taken for light microscopy, protein and DNA determination. We examined the following parameters: number of villi per cm (V/cm), villus height (Vh), number of mitoses per crypt (M/c) and we measured the mucosal protein and DNA content. Nine of 16 rats who received the OKG-free diet had positive cultures but only 3 of 18 rats who received the OKG-enriched diet (P= 0.002). The group on the OKG-enriched diet had a better intestinal mucosal architecture than the group on the OKG-free diet and the studied parameters of the gut mucosa were significantly better: (V/cm: 130 +/- 8.1 vs 99 +/- 7.9, P = 0.001. Vh(mm): 0.40 +/- 0.03 vs 0.24 +/- 0.05, P= 0.002. M/c: 1.71 +/- 0.03 vs 0.34 +/- 0.2, P= 0.001, Protein (mg/cm): 2.300 +/- 0.033 vs 1.207 +/- 0.014, P = 0.002. DNA (microg/cm): 203 +/- 6.41 vs 130 +/- 4.94, P = 0.001. We conclude that OKG-enriched diet prevents the deleterious effects of radiation on intestinal mucosal morphology and integrity, abolishing thus, the increased bacterial translocation observed after abdominal radiation.     

Trophic response of the intestinal mucosa to inflammation in rats injected with turpentine: a study using pair-fed controls

The effects of restricted food intake and acute inflammation on the small bowel were studied, Wistar rats (250 g) were given subcutaneous injections of turpentine (TR) and compared to two control groups, at 18, 42 and 66 h. One was fed ad libitum (C), the other was pair fed (PF) with TR. The TR and PF rats showed hypoplasia of the jejunal mucosa with decreased protein and DNA contents at 42 h and 66 h. The hypoplasia resulted in a reduced villus height that was significantly different from the controls at 66 h (C: 468 +/- 17, TR[66] : 376 +/- 20, PF[66] : 258 +/- 2.9 microm, P<0.001). This decrease in villus height was significantly greater in the PF rats than in the TR rats at 66 h. The crypt height/villus height (C/V) ratio in the PF rats was greater than in the TR group at all times. However, the protein and DNA contents in the TR group were significantly higher than in the PF group at 42 h and 66 h (TR/PF[42] : 29.5 +/- 1.9 vs 20.5 +/- 2.0, P< 0.001, [66]: 25.8 +/- 2.0 vs 16.6 +/- 1.3 mg/10 cm, P,< 0.001). Disaccharidase activities (sucrase and glucoamylase) per 10 cm jejunum at 66 h were significantly lower in the PF group than in the control and TR groups (sucrase mU/10cm[66] C : 3090 +/- 144, TR 2683 +/- 479, PF 1969 +/- 144, P,< 0.001; glucoamylase mU/10 cm[66] 237 +/- 25, TR 169 +/- 40, PF 123 +/- 5, P< 0.01). The N-aminopeptidase patterns in the TR and PF groups were similar. These data suggest that dietary restriction during acute inflammation is the main factor causing hypoplasia of the jejunal mucosa. However, acute inflammation has a trophic effect on the morphological and function of the mucosa. This effect is probably due to inflammatory mediators, whose synthesis is stimulated by turpentine.     

Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats

BACKGROUND: Administration of specific growth factors exert gut-trophic effects in animal models of massive small bowel resection (SBR); however, little comparative data are available. Our aim was to compare effects of a human glucagon-like peptide-2 (GLP-2) analog, recombinant growth hormone (GH) and recombinant keratinocyte growth factor (KGF) on jejunal, ileal, and colonic growth and functional indices after 80% SBR in rats. METHODS: Thirty-seven male rats underwent small bowel transection (sham operation) with s.c. saline administration (control; Tx-S; n = 7) or 80% midjejuno-ileal resection (Rx) and treatment with either s.c. saline (Rx-S, n = 7), GLP-2 at 0.2 mg/kg/d (Rx-GLP-2; n = 8), GH at 3.0 mg/kg/d (Rx-GH; n = 8), or KGF at 3.0 mg/kg/d (Rx-KGF; n = 7) for 7 days. All groups were pair-fed to intake of Rx-S rats. Gut mucosal cell growth indices (wet weight, DNA and protein content, villus height, crypt depth, and total mucosal height) were measured. Expression of the cytoprotective trefoil peptide TFF3 was determined by Western blot. Gut mucosal concentrations of the tripeptide glutathione (L-glutamyl-L-cysteinyl-glycine) and glutathione disulfide (GSSG) were measured by high-performance liquid chromatography and the glutathione/GSSG ratio calculated. RESULTS: SBR increased adaptive growth indices in jejunal, ileal, and colonic mucosa. GLP-2 treatment increased jejunal villus height and jejunal total mucosal height compared with effects of resection alone or resection with GH or KGF treatment. Both GH and KGF modestly increased colonic crypt depth after SBR. SBR did not affect small bowel or colonic goblet cell number or TFF3 expression; however, goblet cell number and TFF3 expression in both small bowel and colon were markedly up-regulated by KGF treatment and unaffected by GLP-2 and GH. SBR oxidized the ileal and colonic mucosal glutathione/GSSG redox pools. GLP-2 treatment after SBR increased the glutathione/GSSG ratio in jejunum, whereas KGF had an intermediate effect. In addition, GLP-2 (but not GH or KGF) prevented the SBR-induced oxidation of the glutathione/GSSG pools in both ileum and colon. Conclusions: GLP-2 exerts superior trophic effects on jejunal growth and also improves mucosal glutathione redox status throughout the bowel after massive SBR in rats. Both GH and KGF increase colonic mucosal growth in this model. KGF alone potently increases gut mucosal goblet cell number and expression of the cytoprotective trefoil peptide TFF3. The differential effects of GLP-2, GH and KGF administration in this model of short bowel syndrome suggest that individual therapy with these growth factors may not be an adequate strategy to maximally improve adaptive gut mucosal growth and cytoprotection after massive small intestinal resection. Future research should address the use of these agents in combination in short bowel syndrome.     

Parenteral nutrition and fasting reduces mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) mRNA in Peyer's patches of mice

BACKGROUND: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) in Peyer's patches (PP) is the gateway molecule for cellular migration into the mucosal immune system. Lack of enteral feeding during parenteral nutrition (PN) rapidly decreases PP MAdCAM-1, leading to drops in mucosal T and B cells and intestinal and respiratory IgA. We determined the molecular events associated with MAdCAM-1 mRNA and protein during PN (short and long term) and fasting (1 and 2 days). METHODS: Experiment 1: Cannulated mice received PN for 8 hours (short-term PN, n = 6) or chow + saline (chow, n = 6). Experiment 2: Cannulated mice received PN (long-term PN, n = 4) or chow (n = 3) for 5 days. Experiment 3: Noncannulated chow mice were fasted for 1 and 2 days (n = 2/time). Total cellular RNA from the PP was quantified for MAdCAM-1 mRNA by real-time polymerase chain reaction (PCR). MAdCAM-1 protein was measured by Western blot. RESULTS: PN rapidly down-regulated MAdCAM-1 gene expression. After 8 hours of PN with lack of enteral feeding, MAdCAM-1 mRNA levels dropped 20% (0.8-fold vs chow, p > .05); 5 days of PN reduced MAd-CAM-1 levels 64% (0.34-fold vs chow, p < .05). PN reduced MAdCAM-1 protein levels by 30% (chow: 329 +/- 14 vs PN: 230 +/- 35, p < .05) after 5 days. Fasting of uncannulated mice decreased MAdCAM-1 mRNA levels by 16% (0.84-fold, p < .05) at day 1 and 30% (0.7-fold, p < .05) by day 2 compared with chow. CONCLUSIONS: Both PN with lack of enteral feeding and fasting down-regulate MAdCAM-1 mRNA and protein levels in PP. The MAdCAM-1 changes are due to lack of enteral stimulation rather than toxic effects of PN.     

Minimal Enteral Nutrition to Improve Adaptation After Intestinal Resection in Piglets and Infants

Background: Minimal enteral nutrition (MEN) may induce a diet‐dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated in patients with short bowel syndrome. Methods: In experiment 1, 3‐day‐old piglets with 50% distal small intestinal resection were fed parenteral nutrition (PN, n = 10) or PN plus MEN given as either colostrum (PN‐COL, n = 5) or formula (PN‐FORM, n = 9) for 7 days. Intestinal nutrient absorption and histomorphometry were performed. In experiment 2, tolerance and feasibility of colostrum supplementation were tested in a pilot study on 5 infants who had undergone intestinal resection, and they were compared with 5 resected infants who served as controls. Results: In experiment 1, relative wet‐weight absorption and intestinal villus height were higher in PN‐COL vs PN (53% vs 23% and 362 ± 13 vs 329 ± 7 µm, P < .05). Crypt depth and tissue protein synthesis were higher in PN‐COL (233 ± 7 µm, 22%/d) and PN‐FORM (262 ± 13 µm, 22%/d) vs PN (190 ± 4 µm, 9%/d, both P < .05). In experiment 2, enteral colostrum supplementation was well tolerated, and no infants developed clinical signs of cow’s milk allergy. Conclusion: Minimal enteral nutrition feeding with bovine colostrum and formula induced similar intestinal adaptation after resection in piglets. Colostrum was well tolerated by newly resected infants, but the clinical indication for colostrum supplementation to infants subjected to intestinal resection remains to be determined.     

Influence of adding pyrroloquinoline quinone to parenteral nutrition on gut-associated lymphoid tissue

Background: Experimental intravenous (IV) parenteral nutrition (PN) diminishes gut‐associated lymphoid tissue (GALT) cell number and function. PN solution cannot maintain GALT at the same level as a normal diet, even when delivered intragastrically (IG). Previous studies demonstrated pyrroloquinoline quinone (PQQ)–deficient mice to be less immunologically responsive. Because standard (STD) PN solution lacks PQQ, PQQ supplementation may prevent PN‐induced GALT changes. This study was designed to determine the influence of adding PQQ to PN on GALT. Methods: In experiment 1, mice (n = 32) were randomized to chow, IV‐STD‐PN, and IV‐PQQ‐PN groups. The chow group was fed chow with the same caloric content as PN. The IV‐STD‐PN group received STD‐PN solution, whereas the IV‐PQQ‐PN group was given PQQ (3 mcg/d)–enriched PN by the IV route. After 5 days of feeding, lymphocytes were isolated from the Peyer's patch (PPs), intraepithelial space (IE), and lamina propria (LP) of the small intestine. GALT lymphocyte number and phenotype (αβTCR+, γδTCR+, CD4+, CD8+, B220+ cells) and intestinal immunoglobulin A (IgA) level were determined. In experiment 2, mice (n = 28) were randomized to IG‐STD‐PN or IG‐PQQ‐PN group. After IG nutrition supports, GALT mass and function were determined as in experiment 1. Results: The IV‐PQQ‐PN group showed increased PP lymphocyte number and PP CD8+ cell number compared with the IV‐STD PN group. The IG‐PQQ‐PN group had significantly greater PP lymphocyte number and PP CD4+ cell numbers than the IG‐STD‐PN group. Neither IV nor IG PQQ treatment raised IgA level. Conclusions: PQQ added to PN partly restores GALT mass, although its effects on GALT function remain unclear.