@article{walter_lin_jacobi_käser_esposito_odle_2019, title={Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages}, volume={10}, ISSN={2049-1891}, url={http://dx.doi.org/10.1186/s40104-019-0321-1}, DOI={10.1186/s40104-019-0321-1}, abstractNote={Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2 (supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation. Day-old pigs (n = 60) were allotted to one of three dietary groups for 21 d (n = 20/diet), and received either a control diet (CON, arachidonate = 0.5% of total fatty acids), an arachidonate (ARA)-enriched diet (LC n-6, ARA = 2.2%), or an eicosapentaenoic (EPA)-enriched diet (LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and mRNA was isolated to assess markers associated with inflammation and eicosanoid production. Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1) oxygen consumption and extracellular acidification (via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation. Concentration of ARA (% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3 (P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA (P < 0.0001), and PGE2 secretion (P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was 1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance (P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation (P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation (P < 0.001) and nitric oxide production (P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet. We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.}, number={1}, journal={Journal of Animal Science and Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Walter, Kathleen R. and Lin, Xi and Jacobi, Sheila K. and Käser, Tobias and Esposito, Debora and Odle, Jack}, year={2019}, month={Feb} }
 @article{jacobi_yatsunenko_li_dasgupta_yu_berg_chichlowski_odle_2016, title={Dietary Isomers of Sialyllactose Increase Ganglioside Sialic Acid Concentrations in the Corpus Callosum and Cerebellum and Modulate the Colonic Microbiota of Formula-Fed Piglets}, volume={146}, ISSN={["1541-6100"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84959288993&partnerID=MN8TOARS}, DOI={10.3945/jn.115.220152}, abstractNote={BACKGROUND
Sialyllactose is a key human milk oligosaccharide and consists of sialic acid (SA) bound to a lactose molecule. Breastfed infants have increased accumulation of ganglioside-bound SA compared with formula-fed infants.


OBJECTIVE
This study aimed to determine whether different isomers of sialyllactose enrich brain SA and modulate the microbiome of developing neonatal piglets.


METHODS
Day-old pigs were randomly allocated to 6 diets (control, 2 or 4 g 3'-sialyllactose/L, 2 or 4 g 6'-sialyllactose/L, or 2 g polydextrose/L + 2 g galacto-oligosaccharides/L; n = 9) and fed 3 times/d for 21 d. Pigs were killed, and the left hemisphere of the brain was dissected into cerebrum, cerebellum, corpus callosum, and hippocampus regions. SA was determined by using a modified periodic acid-resorcinol reaction. Microbial composition of the intestinal digesta was analyzed with the use of 16S ribosomal DNA Illumina sequencing.


RESULTS
Dietary sialyllactose did not affect feed intake, growth, or fecal consistency. Ganglioside-bound SA in the corpus callosum of pigs fed 2 g 3'-sialyllactose or 6'-sialyllactose/L increased by 15% in comparison with control pigs. Similarly, ganglioside-bound SA in the cerebellum of pigs fed 4 g 3'-sialyllactose/L increased by 10% in comparison with control pigs. Significant (P < 0.05, Adonis Test) microbiome differences were observed in the proximal and distal colons of piglets fed control compared with 4-g 6'-sialyllactose/L formulas. Differences were attributed to an increase in bacterial taxa belonging to species Collinsella aerofaciens (phylum Actinobacteria), genera Ruminococcus and Faecalibacterium (phylum Firmicutes), and genus Prevotella (phylum Bacteroidetes) (Wald test, P < 0.05, DeSeq2) compared with piglets fed the control diet. Taxa belonging to families Enterobacteriaceae and Enterococcaceae (phylum Proteobacteria), as well as taxa belonging to family Lachnospiraceae and order Lactobacillales (phylum Firmicutes), were 2.3- and 4-fold lower, respectively, in 6'-sialyllactose-fed piglets than in controls.


CONCLUSIONS
Supplementation of formula with 3'- or 6'-sialyllactose can enrich ganglioside SA in the brain and modulate gut-associated microbiota in neonatal pigs. We propose 2 potential routes by which sialyllactose may positively affect the neonate: serving as a source of SA for neurologic development and promoting beneficial microbiota.}, number={2}, journal={JOURNAL OF NUTRITION}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Yatsunenko, Tanya and Li, Dongpei and Dasgupta, Somsankar and Yu, Robert K. and Berg, Brian M. and Chichlowski, Maciej and Odle, Jack}, year={2016}, month={Feb}, pages={200–208} }
 @article{lin_jacobi_odle_2015, title={Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate}, volume={6}, ISSN={2049-1891}, url={http://dx.doi.org/10.1186/s40104-015-0010-7}, DOI={10.1186/s40104-015-0010-7}, abstractNote={To induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study. Each group of pigs (n = 10) was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were collected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.HPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow (~4.2 μg/mL) and its offspring (~1.5 μg/mL). Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased (P < 0.01) (14)C-accumulation in CO2 and acid soluble products 2.9-fold from [1-(14)C]-oleic acid and 1.6-fold from [1-(14)C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO) activities by 36% and 42% over controls (P < 0.036). The mRNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate (P < 0.0001) but no differences were detected for ACO and PPARα mRNA between the two groups.These data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.}, number={1}, journal={Journal of Animal Science and Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Lin, Xi and Jacobi, Sheila and Odle, Jack}, year={2015}, month={Mar} }
 @article{odle_lin_jacobi_kim_stahl_2014, title={The Suckling Piglet as an Agrimedical Model for the Study of Pediatric Nutrition and Metabolism}, volume={2}, ISSN={2165-8102 2165-8110}, url={http://dx.doi.org/10.1146/annurev-animal-022513-114158}, DOI={10.1146/annurev-animal-022513-114158}, abstractNote={ The neonatal pig ranks among the most prominent research models for the study of pediatric nutrition and metabolism. Its precocial development at birth affords ready adaptation to artificial rearing systems, and research using this model spans a wide array of nutrients. Sophisticated in vitro and in vivo methodologies supporting both invasive, reduction-science research as well as whole-animal preclinical investigations have been developed. Potential applications may dually benefit both agricultural and medical sciences (e.g., “agrimedical research”). The broad scope of this review is to outline the fundamental elements of the piglet model and to highlight key aspects of relevance to various macronutrients, including lipids, carbohydrates, proteins/amino acids, and calcium/phosphorus. The review examines similarities between piglets and infants and also piglet idiosyncrasies, concluding that, overall, the piglet represents an adaptable and robust model for pediatric nutrition and metabolism research. }, number={1}, journal={Annual Review of Animal Biosciences}, publisher={Annual Reviews}, author={Odle, Jack and Lin, Xi and Jacobi, Sheila K. and Kim, Sung Woo and Stahl, Chad H.}, year={2014}, month={Feb}, pages={419–444} }
 @article{jacobi_moeser_blikslager_rhoads_corl_harrell_odle_2013, title={Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets}, volume={19}, ISSN={1007-9327}, url={http://dx.doi.org/10.3748/wjg.v19.i31.5094}, DOI={10.3748/wjg.v19.i31.5094}, abstractNote={AIM
To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.


METHODS
Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses.


RESULTS
Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol.


CONCLUSION
Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.}, number={31}, journal={World Journal of Gastroenterology}, publisher={Baishideng Publishing Group Inc.}, author={Jacobi, S.K. and Moeser, A.J. and Blikslager, A.T. and Rhoads, J.M. and Corl, B.A. and Harrell, R.J. and Odle, J.}, year={2013}, month={Aug}, pages={5094–5102} }
 @article{herfel_jacobi_lin_jouni_chichlowski_stahl_odle_2013, title={Dietary supplementation of Bifidobacterium longum strain AH1206 increases its cecal abundance and elevates intestinal interleukin-10 expression in the neonatal piglet}, volume={60}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/j.fct.2013.07.020}, DOI={10.1016/j.fct.2013.07.020}, abstractNote={Intestinal microbiota of infants differ in response to gestational age, delivery mode and feeding regimen. Dietary supplementation of probiotic bacteria is one method of promoting healthy populations. We examined the impact of a novel probiotic strain of Bifidobacterium longum (AH1206) on the health, growth and development of neonatal pigs as a model for infants. Day-old pigs were fed milk-based formula containing AH1206 at 0, 109, or 1011 CFU/d for 18 d (n = 10/treatment). Differences were not detected in growth, organ weights or body temperatures (P > 0.1); however pigs fed the high dose showed a small (2%) reduction in feed intake. Bacterial translocation was not affected as indicated by total anaerobic and aerobic counts (CFU) in samples of spleen, liver and mesenteric lymph nodes (P > 0.1). Feeding AH1206 had no effects on fecal consistency, but increased the density of B. longum in the cecum. Ileal TNF expression tended to increase (P = 0.08) while IL-10 expression increased linearly (P = 0.01) with supplementation. Based upon findings in the suckling piglet model, we suggest that dietary supplementation with B. longum (AH1206) may be safe for human infants based on a lack of growth, development or deleterious immune-related effects observed in piglets.}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Herfel, Tina M. and Jacobi, Sheila K. and Lin, Xi and Jouni, Zeina E. and Chichlowski, Maciej and Stahl, Chad H. and Odle, Jack}, year={2013}, month={Oct}, pages={116–122} }
 @article{herfel_jacobi_lin_van heugten_fellner_odle_2013, title={Stabilized rice bran improves weaning pig performance via a prebiotic mechanism}, volume={91}, ISSN={0021-8812 1525-3163}, url={http://dx.doi.org/10.2527/jas.2012-5287}, DOI={10.2527/jas.2012-5287}, abstractNote={Stabilized rice bran (SRB) is classified as a "functional food" because of its prebiotic characteristics. With increasing grain prices and the pressure to remove antibiotics from swine diets because of concern over antibiotic resistance, SRB was investigated as a nursery diet ingredient with and without the addition of antibiotics (ANT). Two hundred pigs were weaned at 21 d of age, blocked by BW, and allotted to diets containing 0 or 10% SRB ± ANT according to a 2 × 2 factorial arrangement of treatments. Five animals were housed per pen throughout a 28-d growth period. At the end of the trial, 1 pig from each pen was euthanized for measurement of intestinal morphology. Antibiotic supplementation improved ADG by 6.4% during Phase 2 (d 14 to 28; P = 0.02), but other production variables were unaffected by ANT. During Phase 2 and cumulatively (d 0 to 28), the supplementation of SRB improved G:F by 10% in ANT-free pigs but not in pigs fed ANT (ANT × SRB, P < 0.03). Ileal histology revealed an increase in crypt depth of pigs fed the diet containing ANT plus SRB and corresponding decreases in villi:crypt associated with both ANT and SRB supplementation (P < 0.05). Intraepithelial lymphocytes were increased by 15% in pigs fed SRB without ANT, but were unaffected by SRB in pigs fed ANT (ANT x SRB, P = 0.003). Colonic bifidobacteria tended to increase with SRB supplementation (P < 0.10). Differences in ileal and cecal digesta short-chain fatty acid concentrations were not detected. In summary, SRB improved the efficiency of nutrient utilization in nursery diets lacking antibiotics and tended to increase intestinal bifidobacteria concentrations, indicating that SRB may exert beneficial prebiotic effects in weanling pigs.}, number={2}, journal={Journal of Animal Science}, publisher={Oxford University Press (OUP)}, author={Herfel, T. and Jacobi, S. and Lin, X. and Van Heugten, E. and Fellner, V. and Odle, J.}, year={2013}, month={Feb}, pages={907–913} }
 @article{jacobi_moeser_corl_harrell_blikslager_odle_2012, title={Dietary Long-Chain PUFA Enhance Acute Repair of Ischemia-Injured Intestine of Suckling Pigs}, volume={142}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.111.150995}, DOI={10.3945/jn.111.150995}, abstractNote={Abstract Infant formula companies have been fortifying formulas with long-chain PUFA for 10 y. Long-chain PUFA are precursors of prostanoids, which stimulate recovery of intestinal barrier function. Supplementation of milk with PUFA increases the content of arachidonic acid (ARA) in enterocyte membranes; however, the effect of this enrichment on intestinal repair is not known. The objective of these experiments was to investigate the effect of supplemental ARA on intestinal barrier repair in ischemia-injured porcine ileum. One-day-old pigs (n = 24) were fed a milk-based formula for 10 d. Diets contained no PUFA (0% ARA), 0.5% ARA, 5% ARA, or 5% EPA of total fatty acids. Following dietary enrichment, ilea were subjected to in vivo ischemic injury by clamping the local mesenteric blood supply for 45 min. Following the ischemic period, control (nonischemic) and ischemic loops were mounted on Ussing chambers. Transepithelial electrical resistance (TER) was measured over a 240-min recovery period. Ischemia-injured ileum from piglets fed 5% ARA (61.0 ± 14%) exhibited enhanced recovery compared with 0% ARA (16 ± 14) and 0.5% ARA (22.1 ± 14)-fed pigs. Additionally, ischemia-injured ileum from 5% EPA (51.3 ± 14)-fed pigs had enhanced recovery compared with 0% ARA-fed pigs (P < 0.05). The enhanced TER recovery response observed with ischemia-injured 5% ARA supplementation was supported by a significant reduction in mucosal-to-serosal flux of3H-mannitol and14C-inulin compared with all other ischemia-injured dietary groups (P < 0.05). A histological evaluation of ischemic ilea from piglets fed the 5% ARA showed reduced histological lesions after ischemia compared with the other dietary groups (P < 0.05). These data demonstrate that feeding elevated levels of long-chain PUFA enhances acute recovery of ischemia-injured porcine ileum.}, number={7}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Moeser, Adam J. and Corl, Benjamin A. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2012}, month={May}, pages={1266–1271} }
 @article{campbell_jacobi_liu_robertson_drayton_medina_polo_crenshaw_odle_2012, title={Evaluation of immunoglobulin G absorption from colostrum supplements gavaged to newborn piglets}, volume={90}, ISSN={["1525-3163"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882686007&partnerID=MN8TOARS}, DOI={10.2527/jas.51544}, abstractNote={Absorption of energy and IgG at birth from colostrum may improve survival and immune competency of newborn piglets. Adequate intake of colostrum may be difficult for piglets due to low birth weight, birth order, or viability. This study was designed to evaluate orally fed colostrum supplements with different energy sources and IgG from porcine plasma on piglet serum IgG content and absorption of IgG compared to pooled sow colostrum. Ninety-six newborn piglets from 12 sows with an average birth weight of 1,288 g were used. Eight piglets were removed from each sow immediately at birth, prior to suckling, and randomly allotted to receive either pooled sow colostrum or 1 of 3 colostrum supplements (A, B, and C) fed at 2 dosing schemes. Piglets received their allotted treatment as either one 30-mL dose at 0 h or three 10-mL doses at 0, 2, and 4 h. Piglets received ad libitum access to water at 2-h intervals after receiving their last treatment dose. Twelve hours after the first dose, piglets were weighed and 4 mL of blood was collected. Plasma IgG content, apparent efficiency of absorption, hematocrit, protein, and glucose were determined. Birth weight and final BW did not differ between treatments; however, pigs fed sow colostrum lost more weight (-72 g) than pigs fed colostrum supplements (-40 g; P < 0.001). Differences in hematocrit or serum glucose were not detected. Serum protein was higher (P < 0.05) in piglets fed colostrum supplements than in pigs fed sow colostrum. Serum IgG content did not differ among treatments. Apparent efficiency of IgG absorption was greatest for sow colostrum followed by colostrum supplements B, A, and C (28.5, 27.6, 25.5, and 24.7%, respectively). The single and multiple dose regimes delivered comparable serum IgG whereas the single dose yielded better piglet hydration as noted by less weight loss. In conclusion, all colostrum supplements were comparable in delivering absorbable IgG to the neonatal piglet.}, number={SUPPL4}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Campbell, J. and Jacobi, S. and Liu, Y. and Robertson, K. Hard and Drayton, J. and Medina, I. and Polo, J. and Crenshaw, J. and Odle, J.}, year={2012}, month={Dec}, pages={299–301} }
 @article{liu_chen_odle_lin_jacobi_zhu_wu_hou_2012, title={Fish Oil Enhances Intestinal Integrity and Inhibits TLR4 and NOD2 Signaling Pathways in Weaned Pigs after LPS Challenge}, volume={142}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.112.164947}, DOI={10.3945/jn.112.164947}, abstractNote={Long-chain (n-3) PUFA exert beneficial effects on inflammatory bowel diseases in animal models and clinical trials. In addition, pattern recognition receptors such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain proteins (NOD) play a critical role in intestinal inflammation. We hypothesized that fish oil could alleviate Escherichia coli LPS-induced intestinal injury via modulation of TLR4 and NOD signaling pathways. Twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors included a dietary treatment (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). After feeding fish oil or corn oil diets for 21 d, pigs were injected with LPS or saline. At 4 h postinjection, blood samples were collected and pigs were killed. EPA, DHA, and total (n-3) PUFA were enriched in intestinal mucosa through fish supplementation. Fish oil improved intestinal morphology, indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by decreased plasma diamine oxidase (DAO) activity and increased mucosal DAO activity as well as enhanced protein expression of intestinal tight junction proteins including occludin and claudin-1. Moreover, fish oil decreased intestinal TNFα and PGE(2) concentrations and caspase-3 and heat shock protein 70 protein expression. Finally, fish oil downregulated the mRNA expression of intestinal TLR4 and its downstream signals myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNFα receptor-associated factor 6, and NOD2, and its adaptor molecule, receptor-interacting serine/threonine-protein kinase 2. Fish oil decreased the protein expression of intestinal NFκB p65. These results indicate that fish oil supplementation is associated with inhibition of TLR4 and NOD2 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.}, number={11}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Liu, Yulan and Chen, Feng and Odle, Jack and Lin, Xi and Jacobi, Sheila K. and Zhu, Huiling and Wu, Zhifeng and Hou, Yongqing}, year={2012}, month={Sep}, pages={2017–2024} }
 @misc{jacobi_odle_2012, title={Nutritional Factors Influencing Intestinal Health of the Neonate}, volume={3}, ISSN={["2156-5376"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84872773618&partnerID=MN8TOARS}, DOI={10.3945/an.112.002683}, abstractNote={Dietary nutrients are essential for gastrointestinal (GI) growth and function, and nutritional support of GI growth and development is a significant component of infant care. For healthy full-term neonates, nutritional provisions of the mother's milk and/or formula will support normal maturation of structure and function of the GI tract in most infants. The composition of breast milk affects GI barrier function and development of a competent mucosal immune system. The functional nutrients and other bioactive components of milk support a microenvironment for gut protection and maturation. However, premature infants struggle with feeding tolerance impairing normal GI function, leading to intestinal dysfunction and even death. The high prevalence worldwide of enteric diseases and dysfunction in neonates has led to much interest in understanding the role of nutrients and food components in the establishment and maintenance of a functioning GI tract. Neonates who do not receive enteral feeding as either mother's milk or formula are supported by total parental nutrition (TPN). The lack of enteral nutrition can compound intestinal dysfunction, leading to high morbidity and mortality in intestinally compromised infants. Reciprocally, enteral stimulation of an immature GI tract can also compound intestinal dysfunction. Therefore, further understanding of nutrient interactions with the mucosa is necessary to define nutritional requirements of the developing GI tract to minimize intestinal complications and infant morbidity. Piglet models of intestinal development and function are similar to humans, and this review summarizes recent findings regarding nutrient requirements for growth and maintenance of intestinal health. In particular, this article reviews the role of specific amino acids (arginine, glutamine, glutamate, and threonine), fatty acids (long chain polyunsaturated, medium chain, and short chain), various prebiotic carbohydrates (short-chain fructo-oligosaccharide, fructo--oligosaccharide, lacto-N-neotetraose, human milk oligosaccharide, polydextrose, and galacto-oligosaccharide), and probiotics that have been examined in the suckling piglet model of intestinal health.}, number={5}, journal={ADVANCES IN NUTRITION}, author={Jacobi, Sheila K. and Odle, Jack}, year={2012}, month={Sep}, pages={687–696} }
 @article{jacobi_lin_corl_hess_harrell_odle_2011, title={Dietary Arachidonate Differentially Alters Desaturase-Elongase Pathway Flux and Gene Expression in Liver and Intestine of Suckling Pigs}, volume={141}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.110.127118}, DOI={10.3945/jn.110.127118}, abstractNote={Because dietary arachidonate (ARA) and its eicosanoid derivatives are major regulators of intestinal homeostasis and repair following injury, we evaluated the effects of dietary ARA on desaturation and elongation of (13)C-18:2(n-6) and mRNA abundance of Δ-6-desaturase (FADS2), elongase (ELOVL5), and Δ-5-desaturase (FADS1) in liver and intestine. Day-old pigs (n = 96) were fed milk-based formula containing 0, 0.5, 2.5, or 5% ARA or 5% eicosapentaenoic acid of total fatty acids for 4, 8, and 16 d. In liver, the desaturation rate [nmol/(g tissue⋅h)] of (13)C-18:2(n-6) to (13)C-18:3(n-6) decreased 56% between 4 and 16 d but was not affected by diet. Whereas accumulation in (13)C-20:3(n-6) also decreased with age by 67%, it increased linearly with increasing dietary ARA (P < 0.06). In comparison, intestinal flux was ~50% less than liver flux and was unaffected by age, but desaturation to (13)C-18:3(n-6) increased linearly (by 57%) in pigs fed ARA diets (P < 0.001), equaling the rate observed in sow-fed controls. In both liver and intestine, alternate elongation to (13)C-20:2(n-6) (via Δ-8-desaturase) was markedly elevated in pigs fed the 0% ARA diet compared with all other dietary treatments (P < 0.01). Transcript abundance of FADS2, ELOVL5, and FADS1 was not affected in liver by diet (P > 0.05) but decreased precipitously between birth and d 4 (~70%; P < 0.05). In contrast, intestinal abundance of FADS2 and FADS1 increased 60% from d 4 to 16. In conclusion, dietary ARA regulated the desaturase-elongase pathway in a tissue-specific manner. In liver, ARA had modest effects on (n-6) fatty acid flux, and intestinal FADS2 activity and mRNA increased. Additionally, hepatic flux decreased with postnatal age, whereas intestinal flux did not change.}, number={4}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Lin, Xi and Corl, Benjamin A. and Hess, Holly A. and Harrell, Robert J. and Odle, Jack}, year={2011}, month={Feb}, pages={548–553} }
 @article{lin_bo_oliver_corl_jacobi_oliver_harrell_odle_2011, title={Dietary conjugated linoleic acid alters long chain polyunsaturated fatty acid metabolism in brain and liver of neonatal pigs}, volume={22}, ISSN={0955-2863}, url={http://dx.doi.org/10.1016/j.jnutbio.2010.09.002}, DOI={10.1016/j.jnutbio.2010.09.002}, abstractNote={Effects of dietary conjugated linoleic acid (CLA, 1% mixed isomers) on n-6 long-chain polyunsaturated fatty acid (LCPUFA) oxidation and biosynthesis were investigated in liver and brain tissues of neonatal piglets. Fatty acid β-oxidation was measured in tissue homogenates using [1-14C]linoleic acid (LA) and -arachidonic acid (ARA) substrates, while fatty acid desaturation and elongation were traced using [U-13C]LA and GC-MS. Dietary CLA had no effect on fatty acid β-oxidation, but significantly decreased n-6 LCPUFA biosynthesis by inhibition of LA elongation and desaturation. Differences were noted between our 13C tracer assessment of desaturation/elongation and simple precursor-product indices computed from fatty acid composition data, indicating that caution should be exercised when employing the later. The inhibitory effects of CLA on elongation/desaturation were more pronounced in pigs fed a low fat diet (3% fat) than a high fat diet (25% fat). Direct elongation of linoleic acid to C20:2n-6 via the alternate elongation pathway might play an important role in n-6 LCPUFA synthesis because more than 40% of the synthetic products of [U-13C]LA accumulated in [13C]20:2n-6. Overall, the data show that dietary CLA shifted the distribution of the synthetic products of [U-13C]LA between elongation and desaturation in liver and decreased the total synthetic products of [U-13C]LA in brain by inhibiting LA elongation to C20:2n-6. The impact of CLA on brain LCPUFA metabolism of the developing neonate merits consideration and further investigation.}, number={11}, journal={The Journal of Nutritional Biochemistry}, publisher={Elsevier BV}, author={Lin, Xi and Bo, Jenny and Oliver, Susan A. Mathews and Corl, Benjamin A. and Jacobi, Sheila K. and Oliver, William T. and Harrell, Robert J. and Odle, Jack}, year={2011}, month={Nov}, pages={1047–1054} }
 @article{herfel_jacobi_lin_fellner_walker_jouni_odle_2011, title={Polydextrose Enrichment of Infant Formula Demonstrates Prebiotic Characteristics by Altering Intestinal Microbiota, Organic Acid Concentrations, and Cytokine Expression in Suckling Piglets}, volume={141}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.111.143727}, DOI={10.3945/jn.111.143727}, abstractNote={Oligosaccharides, the 3rd-most abundant component in human milk, are virtually absent from infant formulas and from the cow milk on which most are based. In breast-fed infants, human milk oligosaccharides (HMO) act as both receptor analogs, interfering with pathogen adhesion, and as prebiotics, stimulating the growth of certain commensal bacteria (e.g. bifidobacteria) and supporting the innate immunity. To further align the functional properties of infant formula with those of human milk, polydextrose (PDX) is proposed as a substitute for HMO. To determine the prebiotic functionality of PDX, 1-d-old pigs were fed a cow milk-based formula supplemented with increasing concentrations of PDX (0, 1.7, 4.3, 8.5, or 17 g/L) for 18 d (n = 13). Additional reference groups included pigs sampled at d 0 and sow-reared pigs sampled at d 18 (n = 12). Ileal Lactobacilli CFU, but not Bifidobacteria, increased linearly with increasing PDX (P = 0.02). The propionic acid concentration in digesta linearly increased with the PDX level (P = 0.045) and lactic acid increased linearly by 5-fold with increasing PDX (P = 0.001). Accordingly, digesta pH decreased linearly (P < 0.05) as PDX increased, with a maximal reduction approaching 0.5 pH units in pigs fed 17 g/L. Expression of TNFα, IL-1β, and IL-8 showed a negative quadratic pattern in response to PDX supplementation, declining at intermediate concentrations and rebounding at higher concentrations of PDX. In summary, PDX enrichment of infant formula resulted in a prebiotic effect by increasing ileal lactobacilli and propionic and lactic acid concentrations and decreasing pH with associated alterations in ileal cytokine expression.}, number={12}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Herfel, Tina M. and Jacobi, Sheila K. and Lin, Xi and Fellner, Vivek and Walker, D. Carey and Jouni, Zeina E. and Odle, Jack}, year={2011}, month={Oct}, pages={2139–2145} }
 @article{fry_lloyd_jacobi_siciliano_robarge_spears_2010, title={Effect of dietary boron on immune function in growing beef steers*}, volume={94}, ISSN={["0931-2439"]}, DOI={10.1111/j.1439-0396.2008.00906.x}, abstractNote={Summary}, number={3}, journal={JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION}, author={Fry, R. S. and Lloyd, K. E. and Jacobi, S. K. and Siciliano, P. D. and Robarge, W. P. and Spears, J. W.}, year={2010}, month={Jun}, pages={273–279} }
 @article{herfel_jacobi_lin_walker_jouni_odle_2009, title={Safety evaluation of polydextrose in infant formula using a suckling piglet model}, volume={47}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/j.fct.2009.03.039}, DOI={10.1016/j.fct.2009.03.039}, abstractNote={Oligosaccharides, the third largest component in human milk, are virtually absent from cow's milk and most infant formula. Prebiotic carbohydrates like polydextrose (PDX) have been proposed as surrogates for human milk oligosaccharides. Safety assessments of novel infant formula ingredients include dose-response experiments in appropriate neonatal animal models such as the suckling pig. To further substantiate the safety of the ingredient, one-day old pigs were fed a cow's milk-based formula supplemented with PDX (1.7, 4.3, 8.5 or 17 g/L) for 18 days (n = 13/dose) and compared to appropriate control (unsupplemented formula; n = 13) and reference groups (day 0 pigs, and sow-reared pigs; n = 13). Growth rate, formula intake, stool consistency, behavior score, blood chemistry and hematology, relative organ weights (% of body weight), tissue morphology (i.e. liver, kidney and pancreas) and pancreas biochemistry did not differ among formula-fed pigs (P > 0.1). Polydextrose mimicked other prebiotic carbohydrates and had no adverse effect at the highest tested level 17.0 g PDX/L, equivalent to a dose of 8.35 g/kg of body weight per day.}, number={7}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Herfel, T.M. and Jacobi, S.K. and Lin, X. and Walker, D.C. and Jouni, Z.E. and Odle, J.}, year={2009}, month={Jul}, pages={1530–1537} }
 @article{hess_corl_lin_jacobi_harrell_blikslager_odle_2008, title={Enrichment of Intestinal Mucosal Phospholipids with Arachidonic and Eicosapentaenoic Acids Fed to Suckling Piglets Is Dose and Time Dependent}, volume={138}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.108.094136}, DOI={10.3945/jn.108.094136}, abstractNote={Infant formula companies began fortifying formulas with long-chain PUFA in 2002, including arachidonic acid (ARA) at approximately 0.5% of total fatty acids. The primary objective of this study was to determine the time-specific effects of feeding formula enriched with supra-physiologic ARA on fatty acid composition of intestinal mucosal phospholipids. One-day-old pigs (n = 96) were fed a milk-based formula for 4, 8, or 16 d. Diets contained either no PUFA (0% ARA, negative control), 0.5% ARA, 2.5% ARA, 5% ARA, or 5% eicosapentaenoic acid (EPA) of total fatty acids (wt:wt). Growth (299 +/- 21 g/d) and clinical hematology were unaffected by treatment (P > 0.6). Although minimal on d 4, concentrations of ARA in jejunal mucosa were enriched 47, 272 and 428% by d 8 and 144, 356, and 415% by d 16 in pigs fed the 0.5% ARA, 2.5% ARA, and 5% ARA diets, respectively, compared with the 0% ARA control pigs (P < 0.01). On d 16, ARA enrichment increased progressively with increasing dietary ARA supplementation from 0 to 2.5% but plateaued as dietary ARA rose to 5%. A similar pattern of ARA enrichment was observed in ileal mucosal phospholipids, but maximal enrichment in the ileum exceed that in the jejunum by >50%. As ARA increased, linoleic acid content decreased reciprocally. Although maximal enterocyte enrichment with EPA approached 20-fold by d 8, concentrations were only approximately 50% of those attained for ARA. Negligible effects on gross villus/crypt morphology were observed. These data demonstrate a dose-dependent response of intestinal mucosal phospholipid ARA concentration to dietary ARA with nearly full enrichment attained within 8 d of feeding formula containing ARA at 2.5% of total fatty acids and that supra-physiologic supplementation of ARA is not detrimental to growth.}, number={11}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Hess, Holly A. and Corl, Benjamin A. and Lin, Xi and Jacobi, Sheila K. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2008}, month={Nov}, pages={2164–2171} }
 @article{lyvers peffer_lin_jacobi_gatlin_woodworth_odle_2007, title={Ontogeny of Carnitine Palmitoyltransferase I Activity, Carnitine-Km, and mRNA Abundance in Pigs throughout Growth and Development}, volume={137}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.1093/jn/137.4.898}, DOI={10.1093/jn/137.4.898}, abstractNote={Carnitine palmitoyltransferase (CPT) I catalyzes an important regulatory step in lipid metabolism; however, no studies, to our knowledge, have evaluated the molecular and kinetic [maximal velocity and Michaelis constant (K(m)) for carnitine] ontogeny of CPT I and prevailing tissue concentrations of carnitine in pigs. To this end, hepatic and skeletal muscle tissues were examined at various ages: birth; 24 h; 1, 3, 5, and 8 wk of age; and adult. Hepatic and skeletal muscle CPT I specific activities were low at birth and increased 100 and 70%, respectively, during the first week of life (P < 0.05). Skeletal muscle transcript amounts were 2.7-fold greater (P < 0.001) in 24-h-old pigs relative to newborns, whereas hepatic CPT I mRNA remained constant at each age studied. The apparent K(m) for carnitine decreased 48% (P < 0.05) during the initial 3 wk of life in liver and decreased 40% (P < 0.05) during the first week of life in skeletal muscle. Plasma and liver free carnitine concentrations increased 95 and 62%, respectively, within 24 h after birth (P < 0.05) and hepatic carnitine concentrations remained constant through 5 wk of age. Consequently, hepatic carnitine concentrations were 20-80% greater (P < 0.05) than the K(m) for carnitine during the suckling period. Skeletal muscle carnitine met or exceeded the apparent K(m) for carnitine at each stage of development. Collectively, these findings suggest that postnatal increases in CPT I activity during the suckling period are accompanied by increased tissue carnitine; however, the lack of hepatic CPT I mRNA induction and low activity reported in both tissues prior to 1 wk of age may limit postnatal lipid utilization during the piglet's transition to extra-uterine life.}, number={4}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Lyvers Peffer, Pasha and Lin, Xi and Jacobi, Sheila K. and Gatlin, Lori Averette and Woodworth, Jason and Odle, Jack}, year={2007}, month={Apr}, pages={898–903} }