Dietary Spray-Dried Porcine Plasma Prevents Cognitive Decline in Senescent Mice and Reduces Neuroinflammation and Oxidative Stress.

BACKGROUND: Aging is characterized by chronic, low-grade inflammation that correlates with cognitive decline. Dietary supplementation with spray-dried porcine plasma (SDP) reduces immune activation in rodent models of inflammation and aging. OBJECTIVE: We investigated whether the anti-inflammatory properties of SDP could ameliorate age-related cognitive deterioration and preserve brain homeostasis in an aging mouse model of senescence. METHODS: Male senescence-accelerated prone 8 (SAMP8) mice were used. In Experiment 1, cognitive performance (n  = 10-14 mice/group) was analyzed by the novel object recognition test in 2-mo-old mice (2M group) and in mice fed a control diet or a diet supplemented with 8% SDP for 2 (4M-CTL and 4M-SDP groups) and 4 mo (6M-CTL and 6M-SDP groups). In Experiment 2, the permeability of the blood-brain barrier and junctional proteins in brain tissue was assessed, as well as synaptic density, oxidative stress markers, and inflammatory genes and proteins in mice from the 2M, 6M-CTL, and 6M-SDP groups ( n = 5-11). Statistical analyses included one-factor ANOVA followed by Fisher's posthoc test. RESULTS: 6M-SDP mice had better cognitive performance than 6M-CTL mice in both short-term (P = 0.024) and long-term (P = 0.017) memory tests. In brain tissue, 6M-SDP mice showed reduced brain capillary permeability (P = 0.034) and increased ZO1 and E-cadherin expression (both P <0.04) compared with 6M-CTL mice. SDP also prevented the NFκB activation observed in 6M-CTL mice (P = 0.002) and reduced Il6 expression and hydrogen peroxide concentration (both P <0.03) observed in 6M-CTL mice. SDP also increased the concentration of IL10 (P = 0.027), an anti-inflammatory cytokine correlated with memory preservation. CONCLUSIONS: In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.

Dietary Supplementation with Spray-Dried Porcine Plasma Attenuates Colon Inflammation in a Genetic Mouse Model of Inflammatory Bowel Disease.

Dietary supplementation with spray-dried porcine plasma (SDP) can modulate the immune response of gut-associated lymphoid tissue. SDP supplementation reduces acute mucosal inflammation, as well as chronic inflammation associated with aging. The aim of this study was to analyze if SDP supplementation could ameliorate colitis in a genetic mouse model of inflammatory bowel disease (IBD). Wild-type mice and Mdr1a knockout (KO) mice were administered a control diet or an SDP-supplemented diet from day 21 (weaning) until day 56. The histopathological index, epithelial barrier, and intestinal immune system were analyzed in the colonic mucosa. KO mice had higher epithelial permeability, increased Muc1 and Muc4 expression, and lower abundance of E-cadherin and Muc2 (all p < 0.001). SDP prevented these effects (all p < 0.05) and decreased the colonic inflammation observed in KO mice, reducing neutrophil and monocyte infiltration and activation and the percentage of activated T helper lymphocytes in the colonic mucosa (all p < 0.05). SDP also diminished proinflammatory cytokine expression and increased the anti-inflammatory IL-10 concentration in the colonic mucosa (all p < 0.05). In conclusion, dietary supplementation with SDP enhances colon barrier function and reduces mucosal inflammation in a mouse model of IBD.

Pemafibrate abrogates SLD in a rat experimental dietary model, inducing a shift in fecal bile acids and microbiota composition.

BACKGROUND AND AIMS: Drugs resolving steatotic liver disease (SLD) could prevent the evolution of metabolic dysfunction associated SLD (MASLD) to more aggressive forms but must show not only efficacy, but also a high safety profile. Repurposing of drugs in clinical use, such as pemafibrate and mirabegron, could facilitate the finding of an effective and safe drug-treatment for SLD. APPROACH AND RESULTS: The SLD High Fat High Fructose (HFHFr) rat model develops steatosis without the influence of other metabolic disturbances, such as obesity, inflammation, or type 2 diabetes. Further, liver fatty acids are provided, as in human pathology, both from dietary origin and de novo lipid synthesis. We used the HFHFr model to evaluate the efficacy of pemafibrate and mirabegron, alone or in combination, in the resolution of SLD, analyzing zoometric, biochemical, histological, transcriptomic, fecal metabolomic and microbiome data. We provide evidence showing that pemafibrate, but not mirabegron, completely reverted liver steatosis, due to a direct effect on liver PPARα-driven fatty acid catabolism, without changes in total energy consumption, subcutaneous, perigonadal and brown fat, blood lipids and body weight. Moreover, pemafibrate treatment showed a neutral effect on whole-body glucose metabolism, but deeply modified fecal bile acid composition and microbiota. CONCLUSIONS: Pemafibrate administration reverts liver steatosis in the HFHFr dietary rat SLD model without altering parameters related to metabolic or organ toxicity. Our results strongly support further clinical research to reposition pemafibrate for the treatment of SLD/MASLD.

Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

In vivo studies show that raised aldosterone (Aldo) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased Aldo using human CCD-18Co myofibroblasts and T84 colonic epithelial cells to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa, and transforming growth factor-ß1 (TGF-ß1) was measured by real-time PCR and the expression of junctional complex proteins by Western blot. Aldo stimulated the proliferation of myofibroblasts by 70% (P < 0.05) and increased EGF mRNA expression by 30% (P < 0.05) without affecting VEGFa and TGF-ß1. EGF concentration in the incubation medium increased by 30% (P < 0.05) 24 h after Aldo addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to Aldo was mediated by EGF receptor (EGFR) and involved both MAPKK and phosphatidylinositol 3-kinase pathways. When T84 cells were incubated with medium from myofibroblasts stimulated with Aldo (conditioned medium), the expression of ß-catenin and claudin IV was increased by 30% (P < 0.05) and proliferation by 40% (P < 0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, was present. Results in vivo indicate that rats fed a low-salt diet showed an increased expression of EGF and EGFR in the colonic mucosa. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised Aldo.

Dietary supplementation with spray-dried animal plasma improves vaccine protection in aged mice.

Background: Senescence is characterized by an aggravated inflammatory state that reduces vaccine responsiveness. Dietary supplementation with spray-dried porcine plasma (SDP) exerts anti-inflammatory effects in different mucosal areas. We aimed to determine if the anti-inflammatory properties of SDP improve the efficiency of immunization in senescent animals. Methods: Experiments were performed in 2-month-old and 6-month-old male SAMP8 mice fed control or SDP (8%) feeds for 4 months. The mice received nasal doses of 2.5 µg of Staphylococcus aureus enterotoxin B (SEB) or vehicle every 15 days (i.e., 3 times). Fifteen days after the last dose, a lethal shock was induced by intraperitoneal administration of SEB and LPS. Results: Immunization increased anti-SEB IgA in intestinal and bronchoalveolar fluid (p < 0.05). After the lethal shock, all immunized aged mice that were supplemented with SDP survived, in contrast to only 66% of those fed the control feed (p < 0.05). Moreover, after the lethal challenge, aged mice showed higher expression levels of pro-inflammatory cytokines (Il-6, Tnf-α, Ifn-γ, and Il-1ß) in jejunal and (Tnf-α, and Il-1ß) in lung tissues (p < 0.05), which were reduced by SDP supplementation (p < 0.05). Furthermore, in senescent mice, SDP supplementation augmented Il-4 and Il-10 expression in both tissues (p < 0.05). Conclusion: SDP reduces the mucosal inflammation associated with aging, improving vaccine protection in senescent mice.

The Neuroprotective Effects of Spray-Dried Porcine Plasma Supplementation Involve the Microbiota-Gut-Brain Axis.

Dietary supplementation with spray-dried porcine plasma (SDP) reduces the Alzheimer's disease (AD) hallmarks in SAMP8 mice. Since gut microbiota can play a critical role in the AD progression, we have studied if the neuroprotective effects of SDP involve the microbiota−gut−brain axis. Experiments were performed on two-month-old SAMP8 mice fed a standard diet and on six-month-old SAMP8 mice fed a control diet or an 8% SDP supplemented diet for four months. Senescence impaired short- and long-term memory, reduced cortical brain-derived neurotrophic factor (BDNF) abundance, increased interleukin (Il)-1ß, Il-6, and Toll-like receptor 2 (Tlr2) expression, and reduced transforming growth factor ß (Tgf-ß) expression and IL-10 concentration (all p < 0.05) and these effects were mitigated by SDP (all p < 0.05). Aging also increased pro-inflammatory cytokines in serum and colon (all p < 0.05). SDP attenuated both colonic and systemic inflammation in aged mice (all p < 0.05). SDP induced the proliferation of health-promoting bacteria, such as Lactobacillus and Pediococcus, while reducing the abundance of inflammation-associated bacteria, such as Johnsonella and Erysipelothrix (both q < 0.1). In conclusion, SDP has mucosal and systemic anti-inflammatory effects as well as neuroprotective properties in senescent mice; these effects are well correlated with SDP promotion of the abundance of probiotic species, which indicates that the gut−brain axis could be involved in the peripheral effects of SDP supplementation.

Reply to Nifli, A.-P. Comment on "Rosell-Cardona et al. Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer's Disease Hallmarks in SAMP8 Mice. Nutrients 2021, 13, 2369".

Thank you for your comments on our recent work of the effects of supplementation with spray-dried porcine plasma (SDP) on neuropathological markers of Alzheimer's disease (AD) [...].

Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer's Disease Hallmarks in SAMP8 Mice.

Alzheimer's disease (AD) is characterized by the aberrant processing of amyloid precursor protein (APP) and the accumulation of hyperphosphorylated tau, both of which are accompanied by neuroinflammation. Dietary supplementation with spray-dried porcine plasma (SDP) has anti-inflammatory effects in inflammation models. We investigated whether dietary supplementation with SDP prevents the neuropathological features of AD. The experiments were performed in 2- and 6-month-old SAMP8 mice fed a control diet, or a diet supplemented with 8% SDP, for 4 months. AD brain molecular markers were determined by Western blot and real-time PCR. Senescent mice showed reduced levels of p-GSK3ß (Ser9) and an increase in p-CDK5, p-tau (Ser396), sAPPß, and the concentration of Aß40, (all p < 0.05). SDP prevented these effects of aging and reduced Bace1 levels (all p < 0.05). Senescence increased the expression of Mme1 and Ide1 and pro-inflammatory cytokines (Il-17 and Il-18; all p < 0.05); these changes were prevented by SDP supplementation. Moreover, SDP increased Tgf-ß expression (p < 0.05). Furthermore, in aged mice, the gene expression levels of the microglial activation markers Trem2, Ym1, and Arg1 were increased, and SDP prevented these increases (all p < 0.05). Thus, dietary SDP might delay AD onset by reducing its hallmarks in senescent mice.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

The Anti-Inflammatory Effect of Spray-Dried Plasma Is Mediated by a Reduction in Mucosal Lymphocyte Activation and Infiltration in a Mouse Model of Intestinal Inflammation.

Spray-dried preparations from porcine and bovine plasma can alleviate mucosal inflammation in experimental models and improve symptoms in patients with enteropathy. In rodents, dietary supplementation with porcine spray-dried plasma (SDP) attenuates intestinal inflammation and improves the epithelial barrier function during intestinal inflammation induced by Staphylococcus aureus enterotoxin B (SEB). The aim of this study was to discern the molecular mechanisms involved in the anti-inflammatory effects of SDP. Male C57BL/6 mice were fed with 8% SDP or control diet (based on milk proteins) for two weeks, from weaning until day 33. On day 32, the mice were given a SEB dose (i.p., 25 µg/mouse) or vehicle. SEB administration increased cell recruitment to mesenteric lymph nodes and the percentage of activated Th lymphocytes and SDP prevented these effects). SDP supplementation increased the expression of interleukin 10 (IL-10) or transforming growth factor- ß (TGF-ß) compared to the SEB group. The SEB challenge increased six-fold the expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and intercellular adhesion molecule 1 (ICAM-1); and these effects were attenuated by SDP supplementation. SEB also augmented NF-κB phosphorylation, an effect that was prevented by dietary SDP. Our results indicate that the anti-inflammatory effects of SDP involve the regulation of transcription factors and adhesion molecules that reduce intestinal cell infiltration and the degree of the inflammatory response.

Induction of Colitis in Young Rats by Dextran Sulfate Sodium.

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Dietary glutamine affects mucosal functions in rats with mild DSS-induced colitis.

The development of inflammatory bowel disease may involve immune dysfunction. Because enteral glutamine is the main source of amino acids for the intestinal mucosa and is metabolized at high rates by both enterocytes and immunocytes, the aim of this study was to ascertain the protective role of glutamine supplementation in a DSS-induced model of mild experimental colitis on metabolic, immune, and intestinal variables. Lewis rats were fed diets supplemented with glutamine (glutamine diet, G group) or an isoenergetic isonitrogenous control diet (C group) from postnatal d 21 (weaning) and continuing to d 35. On d 30, half of the rats from both groups were given 0.5% DSS in drinking water (G-DSS and C-DSS groups). Glutamine supplementation increased the plasma concentrations of Thr, Gln, Cit, His, and Arg and enhanced the ratio of essential to nonessential amino acids irrespective of DSS treatment. DSS administration increased the plasma Gln concentration, indicating a reduced utilization of this amino acid by the intestinal tissue. Regarding the gut-associated lymphoid tissue lymphocyte populations, DSS increased the percentages of CD3(+) T lymphocytes from Peyer's patches, NK and B lymphocytes from mesenteric lymph nodes, and NK CD8(-) cells from intraepithelial lymphocytes. The administration of glutamine did not affect the inductive populations nor did it modify T-cell subtypes or the percentage of intraepithelial lymphocytes of gut-associated lymphoid tissue. However, glutamine supplementation reduced the feces water contents in the DSS-treated but not in the untreated rats. These results indicate that glutamine supplementation can improve barrier function in rats with colitis.

Role of vasopressin in rat distal colon function.

The specific role of vasopressin in colonic crypt function and its possible synergistic action with aldosterone were studied. Sprague-Dawley rats fed a high-Na+ (HS; 150 mM NaCl) or a low-Na+ (LS; 150 microM NaCl) diet were deprived of water or infused with vasopressin, and some animals were treated with specific vasopressin receptor subtype V1 and V2 antagonists. The expression of the epithelial Na+ channel (ENaC), alpha-smooth muscle actin (alpha-SMA) and aquaporin-2 (AQP-2) were determined by immunolocalization in distal colonic mucosa. The pericryptal Na+ concentration was determined by confocal microscopy, using a low-affinity Na+-sensitive fluorescent dye (sodium red) and crypt permeability was measured by the rate of escape of fluorescein isothiocyanate-labelled dextran (10 kDa) from the crypt lumen into the pericryptal space in isolated rat distal colonic mucosa. A high plasma concentration of vasopressin raised alpha-SMA expression in the pericryptal sheath (P < 0.05), increased the pericryptal Na+ accumulation in this space (P < 0.01) and caused a reduction of crypt wall permeability (P < 0.01). All these effects were reversed by selective blockade of V1 and V2 receptors. No synergistic effects with aldosterone were observed. Dehydration and vasopressin infusion increased AQP-2 expression in distal colonic mucosa (P < 0.05). This action of vasopressin was prevented by tolvaptan, a specific V2 receptor antagonist (P < 0.05). It is concluded that vasopressin has trophic effects in the rat distal colon, increasing pericryptal myofibroblast growth which affects crypt absorption, and these effects are independent of the presence of aldosterone.

Spray-dried animal plasma prevents the effects of Staphylococcus aureus enterotoxin B on intestinal barrier function in weaned rats.

In this study, we investigated intestinal barrier function during inflammation as well as the effects of dietary supplementation with porcine spray-dried animal plasma (SDAP) proteins and porcine immunoglobulin concentrate (IC). Wistar Lewis rats were fed from d 21 (weaning) until d 34 or 35 either a control diet or a diet containing SDAP or IC. On d 30 and d 33, rats received an intraperitoneal dose of Staphylococcus aureus enterotoxin B (SEB; 0.5 mg/kg body wt; groups SEB, SEB-SDAP, and SEB-IC). SEB reduced the potential difference across the jejunum by 60%, the short-circuit current by 70%, and Na-K-ATPase activity in intestinal mucosa (all P < 0.05). The fluxes of dextran flux (4 kDa) and horseradish peroxidase (HRP, 40 kDa) across the intestinal wall also increased in SEB-treated rats (P < 0.01, P = 0.068, respectively). SEB also increased HRP flux across the paracellular space (P < 0.05). Moreover, SEB-treated rats had a reduced expression of tight junction proteins, such as ZO-1 (10% reduction; P < 0.05) and beta-catenin (20% reduction; P < 0.05). Dietary supplementation with SDAP or IC prevented dextran (P < 0.05) and HRP (P < 0.05) paracellular flux across the intestinal epithelium. SDAP supplementation also prevented SEB effects on Na-K-ATPase activity (P < 0.05). In our model of SEB-induced intestinal inflammation, the increased permeability across the intestinal mucosa was due to the lower expression of tight junction proteins, an effect that can be prevented by both SDAP and IC supplementation.

Heat stress increases apical glucose transport in the chicken jejunum.

In chickens, elevated environmental temperature reduces food intake. We have previously reported that, during heat stress, the intestinal mucosa has an increased capacity to take up sugars. To investigate whether the effects of warm environment on sugar uptake are an intestinal adaptation to lower energy intake or a response attributable to heat stress, we examined the glucose transport kinetics of apical and basolateral membranes of the jejunum and the mucosal morphology of broiler chickens maintained in climatic chambers for 2 wk. Experimental groups were 1) control ad libitum (CAL), fed ad libitum and in thermoneutral conditions (20 degrees C); 2) heat stress ad libitum (HSAL), fed ad libitum and kept in a heated environment (30 degrees C); and 3) control pair-fed (CPF), maintained in thermoneutral conditions and fed the same amount of food as that consumed by the HSAL group. Both the CPF and the HSAL groups showed reduced body weight gain, but only the HSAL chickens had lower plasma thyroid hormones and higher corticosterone than CAL and CPF groups. The fresh weight and length of the jejunum were only reduced in the HSAL group. The activity and expression of apical sodium-dependent glucose transporter 1 (SGLT-1) were increased by approximately 50% in the HSAL chickens, without effects in the CPF group. No changes in K(d) or in SGLT-1 and glucose transporter-2 K(m) were observed in the pair-fed and heated birds. These results support the view that increased intestinal hexose transport capacity is entirely dependent on adaptations of apical SGLT-1 expression to heat stress and is not due to reduced food intake.

Dietary unsaturated long-chain Fatty acids modify D-glucose absorption in weaning rats.

OBJECTIVE: The authors evaluated the effects of dietary long-chain polyunsaturated fatty acids on D-glucose absorption in weaning rats. METHODS: Pups were born from control mothers fed a diet containing (per kg of total fatty acids) 280 g of saturated fatty acids, 496 g of monounsaturated fatty acids and 222 g of polyunsaturated fatty acids or from mothers fed a diet containing a high proportion of saturated fatty acids (920 g/kg) and a low proportion of unsaturated fatty acids (low-unsaturated fatty acid, 80 g/kg), initiated 2 weeks before mating and continued throughout pregnancy. When pups from low-unsaturated fatty acid mothers were 15 days old, they were subdivided into two groups: one control (low-unsaturated fatty acid-C) and one fed a long-chain polyunsaturated fatty acid supplement rich in arachidonic acid and docosahexaenoic acid (low-unsaturated fatty acid-S) until weaning. At day 21, the kinetics of D-glucose absorption was studied in brush-border membrane vesicles from the jejunoileal segment. RESULTS: The maximal transport rate (V(max)) of glucose in the low-unsaturated fatty acid-C and low-unsaturated fatty acid-S groups was higher than in control rats: 160 and 130 versus 98 pmol/(mg protein.s), respectively (P < 0.05). Rats fed the low-unsaturated fatty acid diet had a lower diffusion constant (K(d)) than control rats did: 21.6 and 29.2 nL/(mg protein.s), respectively (P < 0.05). However, rats receiving the long-chain polyunsaturated fatty acid supplement and control rats had similar Kd values. CONCLUSION: These results indicate that dietary long-chain polyunsaturated fatty acid supplementation can restore, in part, the kinetic characteristics of intestinal D-glucose absorption in pups from mothers maintained on a low-unsaturated fatty acid diet.

Induction of colitis in young rats by dextran sulfate sodium.

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Spray-dried porcine plasma reduces the effects of staphylococcal enterotoxin B on glucose transport in rat intestine.

We investigated the intestinal transport of D-glucose (D-Glc) and 3 essential amino acids in a model of intestinal inflammation, and the effects of dietary supplementation with animal plasma proteins on this function. Wistar Lewis rats were fed a diet containing an isonitrogenous amount of milk protein (control group) or a diet supplemented with either spray-dried animal plasma (SDAP) or immunoglobulin concentrate (IC) from porcine plasma, from d 21 of life (weaning) until d 35. On d 30 and 33, rats were challenged intraperitoneally with Staphylococcus aureus enterotoxin B (SEB; groups SEB, SEB-SDAP, and SEB-IC) and on d 35, brush border membrane vesicles (BBMVs) were prepared and used for transport and binding studies. Administration of SEB reduced D-Glc transport across sodium glucose transporter 1 [SGLT1; 20% reduction in maximal transport rate (Vmax); P < 0.05], without affecting the Michaelis constant (Km). The results from specific phlorizin binding, Western blot, and immunohistochemistry supported the view that the effects of SEB are due to reduced expression of D-Glc transporters in the apical membrane. SEB increased the passive diffusion constant (Kd) for D-Glc 3-fold (P < 0.05). SEB did not affect mediated or passive amino acid fluxes of L-leucine, L-methionine, or L-lysine. Dietary SDAP increased the D-Glc Vmax in the SEB group without affecting the passive component. Changes in d-Glc Vmax due to SEB and to the dietary treatments were correlated with changes in the number of SGLT1 transporters present in the BBMVs (r = 0.9468; P < 0.05). Dietary IC had no observed effect. We estimate that, in rats challenged with SEB, SDAP supplementation can increase glucose absorption by 8-9% during the interdigestive periods.

Dietary lipids modify brush border membrane composition and nutrient transport in chicken small intestine.

The influence of dietary fatty acids (FA) on intestinal brush border FA composition and nutrient transport functions was studied in broiler chickens. Ross chicks (2 wk old) were fed for 14 d a standard diet (CTL) or diets enriched with saturated fatty acids (SFA; 60 g/kg lard, LAR diet), (n-3) PUFA (60 g/kg linseed oil, LSO diet) and (n-6) PUFA (60 g/kg sunflower oil, SFO diet). The SFA of the brush border membrane were within 40-44% of total FA in spite of wide variability in dietary SFA concentration (13-32%); membrane (n-6) and (n-3) PUFA strongly reflected their dietary intake and thus the (n-6)/(n-3) ratio. However, the membrane polyunsaturated/saturated ratio (P/S) was close to unity, whereas in the diets, it was between 0.9 and 5. The transport kinetic constants (V(max), K(m), K(d)) of D-glucose (substrate of the sodium glucose cotransporter 1), L-lysine (through systems b(0,+) and y(+)(m)) and L-methionine (through systems B and L) were studied in jejunal brush border membrane vesicles. The changes in dietary FA intake did not affect the K(m) of the substrates for their transporters. Both LAR and SFO diets reduced the D-glucose V(max), which was compensated for by an increase in the K(d). The LAR diet reduced lysine transport across y(+)(m), whereas the LSO diet increased the V(max) for both lysine and methionine.

Dietary plasma protein affects the immune response of weaned rats challenged with S. aureus Superantigen B.

The aim of this study was to determine the potential modulatory effects of diets supplemented with spray-dried animal plasma (SDAP) or immunoglobulin concentrates (IC) on the immune response of rats challenged with Staphylococcus aureus enterotoxin B (SEB). Lewis rats were fed diets containing 80 g of SDAP/kg diet, 22.7 g of IC/kg diet, or milk proteins (Control diet) from postnatal d 21 (weaning) for 14 d. On d 30 and 33, rats were given SEB (0.5 mg/kg body weight; i.p.). Organized gut-associated lymphoid tissue (GALT) populations, intestinal secretion, mucosal and serum immunoglobulin concentrations, and neutrophil infiltration were studied. On d 35, blood was collected under anesthesia and samples of intestinal mucosa, Peyer's patches, mesenteric lymph nodes (MLN), and spleen were taken. SEB increased the water content of feces, which was prevented by diets containing either SDAP (P < 0.002) or IC (P < 0.001), indicating that plasma protein-supplemented diets can reverse the SEB-induced secretory response. In Peyer's patches, the diet containing SDAP partially prevented the SEB-induced increase in T lymphocytes (P < 0.1) and reduced the percentage of activated T helper cells (P < 0.05). In MLN, activated T lymphocytes were increased by SEB but they were not affected by diet. No effects of SEB or dietary supplementation on mucosal IgA and serum IgA and IgG were observed. The effects of SDAP supplementation on the lymphocyte populations of GALT in rats challenged with SEB support the view that SDAP can modulate the immune response and suggest that plasma protein supplementation can prevent GALT from possible activation by luminal bacterial superantigens.