Effect of dietary fiber on microbial activity and microbial gas production in various regions of the gastrointestinal tract of pigs.

The microbial activity, composition of the gas phase, and gas production rates in the gastrointestinal tract of pigs fed either a low- or a high-fiber diet were investigated. Dense populations of culturable anaerobic bacteria, high ATP concentrations, and high adenylate energy charges were found for the last third of the small intestine, indicating that substantial microbial activity takes place in that portion of the gut. The highest microbial activity (highest bacterium counts, highest ATP concentration, high adenylate energy charge, and low pH) was found in the cecum and proximal colon. Greater microbial activity was found in the stomach and all segments of the hindgut in the pigs fed the high-fiber diet than in the pigs fed the low-fiber diet. Considerable amounts of O2 were found in the stomach (around 5%), while the content of O2 in gas samples taken from all other parts of the gastrointestinal tract was < 1%. The highest concentrations and highest production rates for H2 were found in the last third of the small intestine. No methane could be detected in the stomach or the small intestine. The rate of production and concentration of methane in the cecum and the proximal colon were low, followed by a steady increase in the successive segments of the hindgut. A very good correlation between in vivo and in vitro measurements of methane production was found. The amount of CH4 produced by pigs fed the low-fiber diet was 1.4 liters/day per animal. Substantially larger amounts of CH4 were produced by pigs fed the high-fiber diet (12.5 liters/day)(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Microflora on the Free Amino Acid Distribution in Various Regions of the Mouse Gastrointestinal Tract

The distribution of free amino acids in the contents of various regions of the gastrointestinal tract (stomach, upper small intestine, lower small intestine, cecum, upper colon and lower colon) was studied in germfree and conventionalized mice. Particular emphasis was placed on the conversion of tryptophan to indole as a probe for studying intermicrobial interactions and microbe-host interactions in vivo. Great differences were observed in the free amino acid content of the various regions of the digestive tract in each type of mouse and also in any one region between germfree and conventionalized mice. As would be expected, there were fewer differences in amino acid distribution between the types of mice in both regions of the small intestine. This correlates with a much lower population of microorganisms in these regions. The changes in free amino acid content and distribution produced by microflora are great enough to serve as a good probe for studying the interactions of a limited number of species of microbes in gnotobiotic animals and assign possible specific functions to each species.     

Intestinal apical amino acid absorption during development of the pig

Amino acids originating from the diet are the principal metabolic fuels for the small intestine, and although the developing intestine is exposed to dramatic changes in the types and amounts of protein, there is little known about rates of amino acid absorption across the apical membrane during development. Therefore, rates of absorption were measured for five amino acids that are substrates for the acidic (aspartate), basic (lysine), neutral (leucine and methionine), and imino (proline) amino acid carriers using intact tissues from the proximal, mid-, and distal small intestines of pigs ranging in age from 90% of gestation to 42 days after birth (12 days after weaning). Rates of absorption (sum of carrier-mediated and apparent diffusion) were highest at birth (except for proline) and declined by an average of 30% during the first 24 h of suckling. There were continuing declines for leucine, methionine, and proline but not for aspartate and lysine. Due to rapid growth of the intestine, absorption capacities for all amino acids increased faster than predicted from gains in metabolic mass. Regional differences for rates of absorption were not detected until after birth, and only for aspartate and proline. Maximum rates of saturable absorption (nmol. min(-1). mg tissue(-1)) by the midintestine increased during the last 10% of gestation, were highest at birth, and then declined. The contribution of apparent diffusion to amino acid absorption was lowest at birth, then increased after onset of suckling.     

Potential rates of fermentation in digesta from the gastrointestinal tract of pigs: effect of feeding fermented liquid feed

Microbial catabolic capacity in digesta from the gastrointestinal tract of pigs fed either dry feed or fermented liquid feed (FLF) was determined with the PhenePlate multisubstrate system. The in vitro technique was modified to analyze the kinetics of substrate catabolism mediated by the standing stock of enzymes (potential rates of fermentation), allowing a quantitative evaluation of the dietary effect on the catabolic capacity of the microbiota. In total, the potential rates of fermentation were significantly reduced in digesta from the large intestine (cecum, P < 0.1; colon, P < 0.01; and rectum, P < 0.0001) of pigs fed FLF compared to pigs fed dry feed. No effect of diet was observed in the stomach (P = 0.71) or the distal part of the small intestine (P = 0.97). The highest rates of fermentation and the most significant effect of diet were observed for readily fermentable carbohydrates like maltose, sucrose, and lactose. Feeding FLF to pigs also led to a reduction in the large intestine of the total counts of anaerobic bacteria in general and lactic acid bacteria specifically, as well as of microbial activity, as determined by the concentration of ATP and short-chain fatty acids. The low-molecular-weight carbohydrates were fermented mainly to lactic acid in the FLF before being fed to the animals. This may have limited microbial nutrient availability in the digesta reaching the large intestine of pigs fed FLF and may have caused the observed reduction in activity and density of the cecal and colonic microbial population. On the other hand, feeding FLF to pigs reduced the viable counts of coliform bacteria (indicator of Escherichia coli and Salmonella spp.) most profoundly in the stomach and the distal part of the small intestine, probably due to the bactericidal effect of lactic acid and low pH. The results presented clearly demonstrate that feeding FLF to pigs had a great impact on the indigenous microbiota, as reflected in bacterial numbers, short-chain fatty acid concentration, and substrate utilization. However, completely different mechanisms may be involved in the proximal and the distal parts of the gastrointestinal tract. The present study illustrates the utility of the PhenePlate system for quantifying the catabolic capacity of the indigenous gastrointestinal tract microbiota.     

Morphological effects of high dose neomycin sulphate on the small and large intestine

The morphology of the intestinal wall and the activity of certain mucosal enzyme systems in the course of neomycin treatment were evaluated. Conventional and, to study the role of the bacterial flora, germ-free rats received 500 mg neomycin daily by stomach tube. Rats were sacrificed after seven days and small intestine (proximal and distal part) together with segments of the colon were removed and prepared for histochemistry. The colon and proximal small intestine of untreated conventional and germ-free animals did not show appreciable differences in staining activity after treatment with neomycin. Neomycin diminished both in normal and germ-free rats the activity of NAD tetrazolium reductase, succinate dehydrogenase, esterase, alkaline phosphatase and acid phosphatase in the distal small intestine. The findings of this study indicate that explanations for the beneficial effects of neomycin on hyperammonemia in liver disease should not only include the bactericidal action of neomycin but also its influence on absorption and metabolic functions of the mucosal cells.     

Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

Amphotericin B (AmB) is poorly absorbed from the gastrointestinal tract. Recent studies have suggested enhanced drug absorption from solid lipid nanoparticles (SLN). Little is known of the fate of AmB absorption within the gastrointestinal tract, and no gastrointestinal transit study has yet been performed on AmB-containing nano-formulations. We aimed to investigate the effect of food on the gastrointestinal transit properties of an AmB-containing SLN in rats. Three SLNs containing AmB, paracetamol, or sulfasalazine were formulated using cocoa butter and beeswax as lipid matrices and simultaneously administered orally to Sprague-Dawley rats. Paracetamol and sulfapyridine were used as marker drugs for estimating gastric emptying and cecal arrival, respectively. The pharmacokinetic data generated for paracetamol and sulfapyridine were used in estimating the absorption of the AmB SLNs in the small and large intestines, respectively. A delayed rate of AmB absorption was observed in the fed state; however, the extent of absorption was not affected by food. Specifically, the percentages of AmB absorption during the fasted state in the stomach, small intestine, and colon were not significantly different from absorption within the respective regions in the fed state. In both states, however, absorption was highest in the colon and appeared to be a combination of absorption from the small intestine plus absorption proper within the colon. The study suggests that AmB SLN, irrespective of food status, is slowly but predominantly taken up by the lymph, making the small intestine the most favorable site for the delivery of the AmB SLNs.     

Topology of the Na(+)/dicarboxylate cotransporter: the N-terminus and hydrophilic loop 4 are located intracellularly

The current secondary structure model of the Na(+)/dicarboxylate cotransporter, NaDC-1, contains 11 transmembrane domains. The model is based on hydropathy analysis and the extracellular location of the carboxy terminus, which contains an N-glycosylation site. In this study, the model was further tested using indirect immunofluorescence of COS-7 cells. The Flag epitope tag (DYKDDDDK) was fused to the amino terminus of NaDC-1 (Flag-NaDC-1), and a monoclonal antibody against the Flag epitope was used to determine the location of the N-terminus. Hydrophilic loop 4 of NaDC-1 was identified using polyclonal antibodies raised against a fusion protein containing amino acids 164--233 of NaDC-1. The expression of NaDC-1 and Flag-NaDC-1 in COS-7 cells was confirmed by functional assays of succinate transport and by Western blots of cell surface biotinylated proteins. Immunofluorescent labeling of cells expressing both NaDC-1 and Flag-NaDC-1 required permeabilization of the plasma membranes with digitonin whereas no immunofluorescence was visible in intact cells. The results of this study show that both the N-terminus and hydrophilic loop 4 of NaDC-1 are located intracellularly, which supports the current model of NaDC-1 structure.     

Potential Rates of Fermentation in Digesta from the Gastrointestinal Tract of Pigs: Effect of Feeding Fermented Liquid Feed

Microbial catabolic capacity in digesta from the gastrointestinal tract of pigs fed either dry feed or fermented liquid feed (FLF) was determined with the PhenePlate multisubstrate system. The in vitro technique was modified to analyze the kinetics of substrate catabolism mediated by the standing stock of enzymes (potential rates of fermentation), allowing a quantitative evaluation of the dietary effect on the catabolic capacity of the microbiota. In total, the potential rates of fermentation were significantly reduced in digesta from the large intestine (cecum, P < 0.1; colon, P < 0.01; and rectum, P < 0.0001) of pigs fed FLF compared to pigs fed dry feed. No effect of diet was observed in the stomach (P = 0.71) or the distal part of the small intestine (P = 0.97). The highest rates of fermentation and the most significant effect of diet were observed for readily fermentable carbohydrates like maltose, sucrose, and lactose. Feeding FLF to pigs also led to a reduction in the large intestine of the total counts of anaerobic bacteria in general and lactic acid bacteria specifically, as well as of microbial activity, as determined by the concentration of ATP and short-chain fatty acids. The low-molecular-weight carbohydrates were fermented mainly to lactic acid in the FLF before being fed to the animals. This may have limited microbial nutrient availability in the digesta reaching the large intestine of pigs fed FLF and may have caused the observed reduction in activity and density of the cecal and colonic microbial population. On the other hand, feeding FLF to pigs reduced the viable counts of coliform bacteria (indicator of Escherichia coli and Salmonella spp.) most profoundly in the stomach and the distal part of the small intestine, probably due to the bactericidal effect of lactic acid and low pH. The results presented clearly demonstrate that feeding FLF to pigs had a great impact on the indigenous microbiota, as reflected in bacterial numbers, short-chain fatty acid concentration, and substrate utilization. However, completely different mechanisms may be involved in the proximal and the distal parts of the gastrointestinal tract. The present study illustrates the utility of the PhenePlate system for quantifying the catabolic capacity of the indigenous gastrointestinal tract microbiota.     

Protein kinase C-mediated regulation of the renal Na(+)/dicarboxylate cotransporter, NaDC-1.

The Na(+)/dicarboxylate cotransporter of the renal proximal tubule, NaDC-1, reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the tubular filtrate. Although long-term regulation of this transporter by chronic metabolic acidosis and K(+) deficiency is well documented, there is no information on acute regulation of NaDC-1. In the present study, the transport of succinate in Xenopus oocytes expressing NaDC-1 was inhibited up to 95% by two activators of protein kinase C, phorbol 12-myristate, 13-acetate (PMA) and sn-1, 2-dioctanoylglycerol (DOG). Activation of protein kinase A had no effect on NaDC-1 activity. The inhibition of NaDC-1 transport by PMA was dose-dependent, and could be prevented by incubation of the oocytes with staurosporine. Mutations of the two consensus protein kinase C phosphorylation sites in NaDC-1 did not affect inhibition by PMA. The inhibitory effects of PMA were partially prevented by cytochalasin D, which disrupts microfilaments and endocytosis. PMA treatment was also associated with a decrease of approximately 30% in the amount of NaDC-1 protein found on the plasma membrane. We conclude that the inhibition of NaDC-1 transport activity by PMA occurs by a combination of endocytosis and inhibition of transport activity.     

Expression of the peptide transporter hPepT1 in human colon: a potential route for colonic protein nitrogen and drug absorption

Substrates of the proton-coupled peptide transporter, hPepT1, include dietary di- and tripeptides plus therapeutically important drugs such as the beta-lactam antibiotics and angiotensin-converting enzyme inhibitors. Expression and function of hPepT1 in the small bowel is well established. We have compared levels of hPepT1 mRNA expression in regions of human gut by RT-PCR methods and examined the expression of hPepT1 in normal human colon using an anti-hPepT1 antipeptide antibody. hPepT1 mRNA was expressed in the large intestine, although at lower levels than in the small intestine. Quantitatively, expression in ileum was 4.6-fold greater than in sigmoid colon. Immunoreactive hPepT1 was detected in human colon at lower levels than in ileum. The pattern of expression differed between the two tissues: whilst expression in the ileum was localised to the apical enterocyte membrane along the length of the crypt-villus axis, expression in the colonocyte was detected at the apical membrane towards the luminal surface but predominantly at the basal membrane towards the base of the crypt. We conclude that distal regions of the bowel express hPepT1, which may provide a mechanism for colonic protein-nitrogen absorption and for absorption of therapeutically important peptidomimetic drugs.     

Succinate accumulation in pig large intestine during antibiotic-associated diarrhea and the constitution of succinate-producing flora

Succinate was the major organic acid detected in the hindgut content of pigs suffering from antibiotic-associated diarrhea. Antibiotic-associated diarrhea was induced by an oral dose of polymyxin B sulfate (3,000,000 units/day) or an intramuscular injection of enrofloxacin (0.6 g enrofloxacin/day). In the large intestine of enrofloxacin-treated pigs, Gram-negative facultative anaerobic rods phylogenetically related to Escherichia coli and Gram-positive facultative anaerobic non-spore-forming rods phylogenetically related to Lactobacilli were isolated as succinate producers. Succinate-producing Lactobacilli were only isolated as the succinate producer in polymyxin B sulfate-treated pigs. In contrast to antibiotic-associated diarrhea pigs, bacteria belonging to Bacteroidaceae, Fusobacteria, and Enterobacteriaceae were detected as succinate producers in a non-treated pig. In antibiotic-associated diarrhea conditions, antibiotic-resistant Enterobacteria, E. coli in particular, and Lactobacilli may contribute to an abnormal succinate accumulation and may affect water absorption in the hindgut that relates to an expression of antibiotic-associated diarrhea.     

Immunohistochemical analysis of ZnT1, 4, 5, 6, and 7 in the mouse gastrointestinal tract.

Expression of five zinc transporters (ZnT1, 4, 5, 6, and 7) of the Slc30 family in the mouse gastrointestinal tract was studied by immunohistochemical analysis. Results demonstrated unique expression patterns, levels, and cellular localization among ZnT proteins in the mouse gastrointestinal tract with some overlapping. ZnT1 was abundantly expressed in the epithelium of the esophagus, duodenum of the small intestine, and cecum of the large intestine. ZnT4 was predominantly detected in the large intestine. ZnT5 was mainly expressed in the parietal cell of the stomach and in the absorptive epithelium of the duodenum and jejunum. ZnT6 was predominantly detected in the chief cell of the stomach, columnar epithelial cells of the jejunum, cecum, colon, and rectum. Lastly, ZnT7 was observed in all epithelia of the mouse gastrointestinal tract with the highest expression in the small intestine. Expression of ZnT proteins in the absorptive epithelial cell of the gastrointestinal tract suggests that ZnT proteins may play important roles in zinc absorption and endogenous zinc secretion.     

Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets.

Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous. A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet. It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow.     

Degradation of phytate in the gut of pigs ‐ pathway of gastrointestinal inositol phosphate hydrolysis and enzymes involved

The present study gives an overview on the whole mechanism of phytate degradation in the gut and the enzymes involved. Based on the similarity of the human and pigs gut, the study was carried out in pigs as model for humans. To differentiate between intrinsic feed phytases and endogenous phytases hydrolysing phytate in the gut, two diets, one high (control diet) and the other one very low in intrinsic feed phytases (phytase inactivated diet) were applied. In the chyme of stomach, small intestine and colon inositol phosphate isomers and activities of phytases and alkaline phosphatases were determined. In parallel total tract phytate degradation and apparent phosphorus digestibility were assessed. In the stomach chyme of pigs fed the control diet, comparable high phytase activity and strong phytate degradation were observed. The predominant phytate hydrolysis products were inositol phosphates, typically formed by plant phytases. For the phytase inactivated diet, comparable very low phytase activity and almost no phytate degradation in the stomach were determined. In the small intestine and colon, high activity of alkaline phosphatases and low activity of phytases were observed, irrespective of the diet fed. In the colon, stronger phytate degradation for the phytase inactivated diet than for the control diet was detected. Phytate degradation throughout the whole gut was nearly complete and very similar for both diets while the apparent availability of total phosphorus was significantly higher for the pigs fed the control diet than the phytase inactivated diet. The pathway of inositol phosphate hydrolysis in the gut has been elucidated.     

Immunocytochemical and enzyme histochemical localization of kallikrein-like enzymes in colon, intestine, and stomach of rat and cat

Kallikrein was localized in goblet (or mucous) cells of rat colon and in rat and cat small intestine and stomach by two immunocytochemical techniques. A kallikrein-like enzyme was also localized by enzyme histochemistry in mast cells of colon, intestine, and stomach of the cat, where they appeared to be associated with blood vessels in the lamina propria. The mast cell enzyme, however, was not detected by immunocytochemistry using antibodies to kallikrein. Modification in the enzyme histochemical procedure (pH, fixation) yielded positive results for a kallikrein-like protease in goblet cells of the intestine and colon. The possible physiological and pathological significance of kallikrein-like enzyme in the gastrointestinal tract and elsewhere is discussed.     

Immunohistochemical localization of Na+-dependent glucose transporter in the rat digestive tract

Summary Glucose is actively absorbed in the intestine by the action of the Na⁺-dependent glucose transporter. Using an antibody against the rabbit intestinal Na⁺-dependent glucose transporter (SGLT1), we examined the localization of SGLT1 immunohistochemically along the rat digestive tract (oesophagus, stomach, duodenum, jejunum, ileum, colon and rectum). SGLT1 was detected in the small intestine (duodenum, jejunum and ileum), but not in the oesophagus, stomach, colon or rectum. SGLT1 was localized at the brush border of the absorptive epithelium cells in the small intestine. Electron microscopical examination showed that SGLT1 was localized at the apical plasma membrane of the absorptive epithelial cells. SGLT1 was not detected at the basolateral plasma membrane. Along the crypt-villus axis, all the absorptive epithelial cells in the villus were positive for SGLT1, whose amount increased from the bottom of the villus to its tip. On the other hand, cells in the crypts exhibited little or no staining for SGLT1. Goblet cells scattered throughout the intestinal epithelium were negative for SGLT1. These observations show that SGLT1 is specific to the apical plasma membrane of differentiated absorptive epithelial cells in the small intestine, and suggest that active uptake of glucose occurs mainly in the absorptive epithelial cells in the small intestine.     

Conformationally sensitive residues in extracellular loop 5 of the Na+/dicarboxylate co-transporter

The Na+/dicarboxylate co-transporter, NaDC-1, from the kidney and small intestine, transports three sodium ions together with one divalent anion substrate, such as succinate2-. A previous study (Pajor, A. M. (2001) J. Biol. Chem. 276, 29961-29968), identified four amino acids, Ser-478, Ala-480, Ala-481, and Thr-482, near the extracellular end of transmembrane helix (TM) 9 that are likely to form part of the permeation pathway of the transporter. All four cysteine-substituted mutants were sensitive to inhibition by the membrane-impermeant reagent [2-(trimethylammonium)ethyl]-methanethiosulfonate (MTSET) and protected by substrate. In the present study, we continued the cysteine scan through extracellular loop 5 and TM10, from Thr-483 to Val-528. Most cysteine substitutions were well tolerated, although cysteine mutations of some residues, particularly within the TM, produced proteins that were not expressed on the plasma membrane. Six residues in the extracellular loop (Thr-483, Thr-484, Leu-485, Leu-487, Ile-489, and Met-493) were sensitive to chemical labeling by MTSET, depending on the conformational state of the protein. Transport inhibition by MTSET could be prevented by substrate regardless of temperature, suggesting that the likely mechanism of substrate protection is steric hindrance rather than large-scale conformational changes associated with translocation. We conclude that extracellular loop 5 in NaDC-1 appears to have a functional role, and it is likely to be located in or near the substrate translocation pore in the protein. Conformational changes in the protein affect the accessibility of the residues in extracellular loop 5 and provide further evidence of large-scale changes in the structure of NaDC-1 during the transport cycle.     

Glucagon-like peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs

Exogenous glucagon-like peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87-91% of gestation) with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and brush border membrane vesicles, except for lysine. Administration of exogenous GLP-2 to preterm TPN-fed pigs similarly did not increase rates of nutrient absorption, yet nutrient absorption capacities of the entire small intestine tended to increase (+10-20%, P < 0.10) compared with TPN alone due to increased intestinal mass (+30%, P < 0.05). GLP-2 infusion did not increase sodium-glucose cotransporter-1 mRNA abundance in fetuses or postnatal preterm pigs. Hence, the efficacy of exogenous GLP-2 to improve nutrient absorption by the intestine of fetal and preterm pigs is limited compared with term pigs and more mature animals and humans.     

Dietary α-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets

Neonates are at increased risk for inflammatory bowel disease, but effective prevention and treatments are currently limited. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of dietary supplementation with α-ketoglutarate (AKG) on the intestinal morphology and function. Eighteen 24-day-old pigs (weaned at 21 days of age) were assigned randomly to control, LPS, and LPS + AKG groups. The piglets in the control and LPS groups were fed a corn- and soybean meal-based diet, whereas the LPS + AKG group was fed the basal diet supplemented with 1% AKG. On days 10, 12, 14, and 16, piglets in the LPS and LPS + AKG groups received intraperitoneal administration of LPS (80 μg/kg BW), whereas piglets in the control group received the same volume of saline. On day 16, d-xylose was orally administrated to all pigs at the dose of 0.1 g/kg BW, 2 h after LPS or saline injection, and blood samples were collected 3 h thereafter. Twenty-four hours post-administration of LPS or saline, pigs were killed to obtain intestinal mucosae for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) protein levels, the ratio of villus height to crypt depth, and the ratio of phosphorylated mTOR to total mTOR in duodenal, jejunal, and ileal mucosa. These adverse effects of LPS were attenuated (P < 0.05) by AKG supplementation. Moreover, AKG prevented the LPS-induced increase in intestinal HSP70 expression. Collectively, these novel results indicate that dietary supplementation with 1% AKG activates the mTOR signaling, alleviates the mucosal damage, and improves the absorptive function of the small intestine in LPS-challenged piglets. The findings not only help understand the mode of AKGs actions in the neonatal gut but also have important implications for infant nutrition under inflammatory conditions.