A series of medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) with enriched 3-hydroxynonanoate (HN) content (up to 95.8 mol% compared to 68.6 mol% without acrylic acid) or 3-hydroxyoctanoate (HO) content (up to 97.5 mol% compared to 88.0 mol% without acrylic acid) was produced in continuous culture by co-feeding fatty acid and glucose plus inhibiting fatty acid β-oxidation using acrylic acid. Using a similar feeding strategy in fed-batch fermentation, similar monomeric compositions but a higher biomass concentration and PHA content could be obtained. However, at a lower growth rate (0.15 h-1 vs. 0.25 h-1), the biomass concentration and PHA content could be greatly enhanced from 17.1 to 71.4 g L-1 and from 64.4 to 75.5%, respectively, while the HN content decreased slightly from 92.2 to 88.9 mol%. PHAs produced under acrylic acid inhibition possessed improved physical properties including a higher melting point, faster crystallization rate, and greater tensile strength at break and Young’s modulus. Two recovery methods were developed for the recovery of MCL-PHA from Pseudomonas putida KT2440. One applied acetone extraction which was capable of recovering all the PHA from the cells with a purity of 91.6% and no detectable polymer molecular weight loss using Soxhlet extraction. Further purification was achieved by redissolving in acetone and reprecipitating in cold methanol. The other method used sodium hydroxide to solubilize the non-PHA cellular material. PHA purity of about 85% was obtained from a biomass containing 65.6% PHA after treatment with 0.2 N NaOH at 22 ± 1oC for 2 h or with 0.1 N at 80 ± 1oC for 15 min. However, a treatment at 22 ± 1oC followed by a second NaOH treatment at 80 ± 1oC resulted in higher PHA purity (94.7%) with a recovery efficiency of 88%. Under these conditions, NaOH digestion had a negligible effect on PHA molecular weight. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2010-08-30 22:44:44.501

In vivo production of medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHA) containing a side chain carboxyl group from azelaic acid (AzA), a nine-carbon α,ω-dicarboxylic acid, was investigated using Pseudomonas citronellolis DSM 50332 in a phosphate (P)-limited chemostat. Co-feeding with nonanoic acid (NA) and inhibition of β-oxidation with acrylic acid (AA) were strategies that were used to stimulate the incorporation of carboxylated monomers, but both were unsuccessful. P. citronellolis DSM50332 was capable of growing on AzA as a sole source of carbon and energy, indicating that enzymes in β-oxidation utilized AzA and its derivatives. However, the MCL-PHA produced from AzA comprised 3-hydroxyoctanoate (C8) and 3-hydroxydecanoate (C10) monomers, which was consistent with precursor supplied via the de novo fatty acid biosynthesis pathway. This evidence suggests that one or more of 3-ketoacyl-CoA reductase (FabG), enoyl-CoA hydratase (PhaJ) and PHA synthase (PhaC) of this organism do not have the low specificity required to utilize a carboxylated substrate. Future work involving mutations may broaden the substrate specificity of these key enzymes to overcome this obstacle. Two-stage high-cell density carbon (C)-limited chemostat cultivation of P. putida KT2440 was examined for MCL-PHA production from nonanoic acid (NA) at high intracellular polymer content and volumetric productivity. Growth conditions stimulating good PHA production were first established in single-stage chemostat, which yielded 63.1 wt% PHA containing 90 mol% C9 units and a productivity of 1.52 g L-1h-1 at a dilution rate of 0.30 h-1. This productivity was higher than any value reported in literature for continuous MCL-PHA production systems and comparable to the upper range of fed-batch results. Two-stage production yielded promising results, notably the increase in polymer content from the first to second stage. However, complications involving foaming and an unexplained decline in PHA content adversely affected system performance. The best PHA content and overall productivity were 58.5 wt% and 0.76 g L-1h-1, respectively. Nonetheless, the results demonstrate the potential to achieve high PHA content without the need for pure oxygen at high dilution rates, warranting further investigation focusing on the optimization of growth conditions. / Thesis (Master, Chemical Engineering) -- Queen's University, 2011-12-19 15:48:21.808

Résumé : Le vieillissement de la population est relié à l’augmentation de la présence de certaines maladies comme les déclins cognitifs ou les démences de type Alzheimer. Chez les personnes à risques de développer ces démences, une diminution précoce du métabolisme cérébral du glucose peut être observée avant même l’apparition des premiers symptômes. Ce déficit énergétique pourrait expliquer la cascade qui mène au développement des déclins cognitifs. Les cétones sont des molécules produites par le corps à partir de la lipolyse des acides gras qui ont déjà démontré leur efficacité comme substrat énergétique de substitution pour le cerveau. L’utilisation de triglycérides de moyennes chaînes (MCT), des acides gras facilement absorbables et oxydables, est un moyen efficace pour augmenter les cétones rapidement mais transitoirement. Notre objectif était de voir s’il était possible d’augmenter les cétones plasmatiques et de maintenir une concentration modérée sur 24 h avec une supplémentation quotidienne en MCT. Dix participants ont d’abord reçu une supplémentation de 2 semaines d’une émulsion de MCT (3 fois par jour). Leur concentration plasmatique de cétones mais aussi de glucose, de cholestérol, de triglycérides et d’acides gras libres était mesurée au début et à la fin de la supplémentation. Huit participants ont par la suite reçu une supplémentation de 4 semaines de l’émulsion de MCT (4 fois par jour). En plus des paramètres mentionnés précédemment, des mesures d’oxydation de MCT, à l’aide d’un traceur 13C-trioctanoate, d’oxydation des cétones, à l’aide d’un traceur de 13C-bêta-hydroxybutyrate ((30Hb), et des mesures de composition corporelle étaient effectuées. Dans les deux études, les analyses plasmatiques ont démontré une augmentation significative des cétones plasmatiques (jusqu’à 0,47 ± 0 ,1 5 mM), qui semblait plus soutenue lors de la deuxième étude. Aucune autre modification n’a été observée dans les analyses plasmatiques. Une diminution de l’oxydation du traceur 13C-trioctanoate dans les heures suivant la prise puis une hausse à 24 h suivant la supplémentation montre un changement dans l’utilisation des MCT, donc une plus grande conversion en cétones. Aucun changement n’a été observé avec le traceur 13C-(30Hb. Aucune variation de la composition corporelle n’a été observée. Ces études montrent la capacité des MCT à augmenter et à maintenir une concentration de cétones durant 24 h à des niveaux légers chez un adulte en santé. // Abstract : Aging leads to the development of many diseases among which is cognitive decline associated with dementia and Alzheimer's disease (AD). In populations who are at risk of developing cognitive decline, it has been noted that a marked brain glucose hypometabolism precedes the onset of other clinical symptoms such as [beta]-amyloid accumulation. This hypometabolism could therefore be responsible for the development of AD. Ketone bodies are energetic molecules that are produced by the liver following the (3-oxidation of fatty acids. They already have been showed to be able to sustain brain metabolism as the principal energy source. Medium chain triglycerides (MCT) are easily absorbed and metabolised fatty acids. They can raise plasma ketones rapidly but transiently. Our objective was to determine whether it was possible to raise and maintain a moderate plasma ketone concentration over 24 h in healthy adults. Ten participants were first given a 2 week supplementation of MCT (3 times a day). Plasma ketone, glucose, cholesterol, triglyceride and free fatty acids were measured. Another 8 participants were given a 4 week supplementation of MCT (4 times a day). In addition to the measures taken in the first project, MCT oxidation; with [indice supérieur 13] C-trioctanoate, ketone oxidation; with [indice supérieur 13] C-beta-hydroxybutyrate and body composition were measured. In both projects, plasma ketone concentration were raised (to a maximum of 0.48 ± 0.15 mM) and appeared to be more stable in the second project. All other plasma measures were unchanged. Significantly lower [indice supérieur 13] C-trioctanoate oxidation was detected during the 2 to 5 hours following the tracer absorption after the supplementation and a marked augmentation was detected 24 h following the supplementation. This indicates a shift in MCT utilization by the body from immediate energy source to ketone precursor. No changes were noted in [beta]OHb oxidation or in body composition. These studies show the ability of MCT to raise and maintain a moderate level of ketones in plasma when taken daily in healthy adults.

Le cerveau humain est un organe très métaboliquement actif. Cet énorme besoin énergétique l’expose à un risque accru de détérioration causée par un dérèglement de ce métabolisme. Dans la phase précoce de la maladie d’Alzheimer, un hypométabolisme cérébral du glucose est observé. Cette carence énergétique serait à l’origine des détériorations observée lors du développement de cette maladie. Le cerveau a accès à une autre source endogène d’énergie : les cétones. Les cétones sont particulièrement importantes pour le cerveau puisqu’il ne possède pas la capacité d’utiliser les acides gras comme source énergétique à l’instar des autres organes. Les cétones sont issues de la β-oxydation hépatique des acides gras. Ils sont produits en situation de jeûne lorsque les niveaux circulants de glucose et d’insuline sont bas. Les cétones se sont déjà montré efficaces dans le traitement de divers troubles neurologiques comme l’épilepsie. Par contre, outre les diètes cétogènes et le jeûne prolongé, il n’existe pas de traitement efficace pour maintenir une cétonémie modérée chez l’adulte. Le métabolisme énergétique cérébral en situation de cétose modérée reste encore mal compris dans cette population. Les travaux de cette thèse se sont donc concentrés à étudier la possibilité d’une combinaison d’approche nutritionnelle et pharmacologique afin de stimuler la cétogenèse chez l’adulte. Ils ont aussi exploré les changements de métabolisme cérébral chez l’adulte durant une cétose modérée. L’objectif de la première étude était d’étudier le potentiel du bezafibrate à stimuler la cétogenèse induite par une supplémentation en triglycérides de moyennes chaînes (MCT). Cette première étude a démontré que le bezafibrate avait peu d’effet sur la stimulation de la cétogenèse induite par les MCT et que le facteur limitant dans cette stimulation était donc la disponibilité des substrats et non la capacité cétogène des cellules hépatiques. L’objectif de la seconde étude était d’étudier les changements de capture des cétones et du glucose au cerveau durant un état de cétose modérée chez l’adulte. Les résultats de cette deuxième étude ont montré que la capture des cétones au cerveau est directement proportionnelle à leur concentration plasmatique. Cette étude a aussi démontré que la capture cérébrale des cétones était directement reliée à leur concentration plasmatique alors que la capture cérébrale du glucose est modulée par les besoins énergétiques du cerveau. Une stimulation cétogénique chez des personnes atteintes de déclin cognitif pourrait donc aider à rétablir la balance énergétique et ralentir l’apparition des symptômes chez ces personnes mais cet effet devra être étudié dans une étude ultérieure. / Abstract : The human brain is the most metabolically active organ of the body. This high need for energy exposes it to an increase risk in case of hypometabolism. Such a glucose hypometabolism is seen during the early stages of Alzheimer’s disease. This factor is believed to be one of the cause of the disease. Ketones are the main alternate substrate for the human brain. Ketones are particularly important since, unlike other organs, the brain can not use fatty acids as alternative fuel. Ketones are mainly produce through β-oxidation of fatty acid by the liver. This happens mainly during fasting when circulating levels of glucose and insulin are low. Studies have shown that ketones can have a therapeutic effect in a variety of neurological diseases, mainly epilepsy and Alzheimer’s disease. Nevertheless, apart from ketogenic diet and prolonged fasting, there is currently no effective ways to induce and maintain moderate ketosis in adults. Brain energy metabolism under moderate ketosis remains also misunderstood in this population. This thesis aimed look at the effect of a combination of a pharmacological treatment and a nutritional supplementation to induce moderate sustain ketosis in adults. It also studied the effect of a moderate ketosis on brain energy metabolism in adults. The aim of the first study was to study the effect of a pharmacological treatment, bezafibrate, on the potentiation of the ketogenic effect induced by a medium-chain triglycerides (MCT) supplementation. The results of this study that bezafibrate had little effect on the ketosis induced by a MCT supplementation and, therefore, that the limiting factor in human ketosis was not the liver cells capacity to produce ketones but the availability of substrates for ketogenesis. The aim of the second study was to study the impact of a nutritional moderate ketosis on brain glucose and ketone uptake. The results of this study showed a direct correlation between brain ketone uptake and plasma ketone concentrations. This study also showed that brain ketone uptake is regulated by blood ketone concentration whereas brain glucose uptake is regulated by the brain energy needs. Further studies should then look if such a moderate ketosis induced in cognitively impaired patients could re-equilibrate the energy balance in the brain and then slow the apparition of clinical symptoms in this population.

Doctor of Philosophy / Department of Animal Sciences and Industry / Cassandra K. Jones / Porcine epidemic diarrhea virus (PEDV) is a heat-sensitive virus that devastated the United States swine industry. Because of its heat sensitivity, it was hypothesized that a pellet mill mimicking commercial thermal processing may mitigate PEDV infectivity. From the results, it was determined that a conditioning time of 30 sec or greater and temperatures above 54.4°C were effective point-in-time kill steps to inactive PEDV in a research setting. However, this does not prevent subsequent recontamination after pelleting as it is a point-in-time mitigation step. To further explore this, various mitigation additives were evaluated to prevent or mitigate PEDV post-pellet contamination in swine feed and ingredients. Various additives were examined across 3 experiments and included mitigation additives of medium chain fatty acids (MCFA), organic acids (OA), essential oils (OA), formaldehyde based products, and sodium bisulfate. From Exp. 1, formaldehyde, medium chain fatty acids (MCFA), essential oils (EO), and organic acid (OA) each decreased detectable PEDV RNA compared to the control (P<0.05). Additionally, PEDV stability over time was influenced by matrix as the meat and bone meal and spray-dried animal plasma resulted in a greater (P<0.05) quantity of detectable PEDV RNA over 42 days compared to that of the swine diet and blood meal. In Exp. 2, the 1% MCFA inclusion was equally effective at mitigating PEDV as a commercially available formaldehyde product in the complete swine diet. To further explore the effects of MCFA against PEDV, Exp. 3 was conducted to evaluate lower inclusion levels of MCFA and fat sources containing MCFA. It was noted that formaldehyde, 1% MCFA (1:1:1: of caproic, caprylic, and capric acids), 0.66% caproic, 0.66% caprylic, and 0.66% capric acids enhance the RNA degradation of PEDV in swine feed as determined by a bioassay. The MCFA were also evaluated against Salmonella Typhimurium, Generic Escherichia coli, Enterotoxigenic Escherichia coli, and Campylobacter coli. It was noted that the efficacy of the MCFA varied between each bacteria species with caproic and caprylic being the most effective. Commercial developmental products were also tested and determined that Product A and B provided the lowest MIC values across Salmonella Typhimurium, Generic Escherichia coli, and Enterotoxigenic Escherichia coli (P < 0.05). Product A and B were further tested in an animal disease trial utilizing a strain of enterotoxigenic Escherichia. coli O149:K91: K88. From d 7 to 14, chlortetracycline, 1:1:1 blend, and Product B, all improved G:F compared to the control (P<0.05). This also led to chlortetracycline and Product B having an improvement (P<0.05) over the control diet from d 0 to 14. A treatment × day interaction for the enterotoxigenic E. coli plate scores was observed (P < 0.05), which occurred because of the decrease (P<0.05) in plate scores for Product B from d 1 to d 14 and an increase (P<0.05) in chlortetracycline from d 7 to 14. A decrease (P<0.05) in plasma urea nitrogen and haptoglobin was observed as time increased from d -2 to 14. In summary MCFA have shown to be an effect interventional mitigation strategy against PEDV and various bacteria.

Dietary lipids determine the incorporation and fatty acid composition of the organism, especially in organs most susceptible to its modulating action on membrane phospholipids esterified fatty acids, such as the liver. Ketogenic diets, widely used to treat various disorders, often use long-chain triacylglycerols, however, medium chain triglycerides are considered an alternative source, since they are digested, absorbed, oxidized and removed from circulation more rapidly than long chain triacylglycerols. In addition, it lead to the formation of ketone bodies quickly, without the influence of hormonal or nutritional factors. To contribute to the discussion, this paper presents a review chapter, entitled Mitochondrial dysfunction in nonalcoholic fatty liver disease, which gathers information on oxidative stress and consequent mitochondrial dysfunction in the context of liver disease. It also presents an original article, entitled Fatty acid profile in liver tissue of rats subjected to ketogenic diet rich in trienantin, which discusses the effects of a ketogenic diet based on trienantin, a homogeneous triacylglycerol composed of enantic (heptanoic) acid, or based on soybean oil on this profile. The livers of animals fed the ketogenic diet showed a significant reduction in the concentration of monounsaturated fatty acids, 9-hexadecenoic and 9-octadecenoic compared to control group, suggesting a potential reduction in the activity of the enzyme Stearoil-CoA Desaturase 1. Additionally, the group fed trienantin showed increased levels of octadecanoic acid compared to control group, which corroborated the hypothesis of decreased enzyme activity in this group. Thus trienantin in ketogenic proportions exerted modulatory effects similar to soybean oil, widely used conventional oil, despite the differences in fatty acid composition between these two fat sources. The study showed that rats fed a ketogenic diet experienced modulation of fatty acid profile of hepatic lipids and that in the conditions set forth herein, this modulation was due especially to the nature of the ketogenic diet itself and not to the type of oil used in their preparation. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os lipídios dietéticos determinam a incorporação e a composição em ácidos graxos do organismo, especialmente em órgãos mais susceptíveis a sua ação moduladora sobre os ácidos graxos esterificados a fosfolipídios de membrana, como, por exemplo, o fígado. Dietas cetogênicas, amplamente utilizadas para o tratamento de diversas desordens, normalmente utilizam triacilgliceróis de cadeia longa, porém, triacilgliceróis de cadeia média são considerados uma fonte alternativa, visto que são digeridos, absorvidos, oxidados e removidos da circulação mais rapidamente que os de cadeia longa. Além disso, levam à formação de corpos cetônicos de forma acelerada, não sofrendo a influência de fatores hormonais ou nutricionais. Visando contribuir com a discussão, a presente dissertação apresenta um capítulo de revisão, intitulado Disfunção mitocondrial na doença do fígado gorduroso não alcoólica, que reúne informações sobre o estresse oxidativo e a conseqüente disfunção mitocondrial, no contexto desta doença hepática. E, um artigo original, intitulado Perfil em ácidos graxos do tecido hepático de ratos submetidos à dieta cetogênica rica em trienantina, que discute os efeitos de dieta cetogênica à base de trienantina, um triacilglicerol homogêneo do ácido enântico (heptanóico), ou de óleo de soja, sobre tal perfil. Os fígados dos animais alimentados com as dietas cetogênicas apresentaram redução significativa na concentração de ácidos graxos monoinsaturados, 9-hexadecenóico e 9-octadecenóico, quando comparados ao grupo Controle, sugerindo uma possível redução na atividade da enzima Estearoil-CoA Dessaturase 1. Adicionalmente, o grupo alimentado com trienantina apresentou aumento dos níveis de ácido octadecanóico, quando comparado ao grupo Controle. Assim, a trienantina, em proporções cetogênicas, exerceu efeito modulador similar ao do óleo de soja, um óleo convencional largamente utilizado, apesar das diferenças na composição em ácidos graxos entre essas duas fontes lipídicas. Neste estudo constatou-se que os ratos alimentados com dieta cetogênica sofreram modulação do perfil em ácidos graxos dos lipídios hepáticos e que, nas condições aqui estabelecidas, tal modulação se deveu especialmente à natureza cetogênica da dieta per si e não ao tipo de óleo empregado em sua elaboração.

Medium chain fatty acids (MCFAs) are essential molecules for a wide range of pharmaceutical, biotechnological, and industrial applications. These are naturally occurring saturated or unsaturated fatty acids containing 6-12 carbons with complex and pH sensitive aggregation. Medium chain fatty acids such as capric acid (C10) or lauric acid (C12) have additionally been shown to exhibit antibacterial activity. A number of studies have observed the aggregation behavior of long chain fatty acid using the titration curves by molecular dynamic (MD) simulations.  In this study, we performed constant-pH coarse-grained MD simulations to determine pKa values and titration behavior using a two-states model for C10 and C12. In the simulations, pH was varied between 2 to 8 and pKa values were determined using the Hill equation. The pKa for C10 (capric acid) was found to be 4.8 and for C12 (lauric acid) 5.4, in good agreement with the literature values (4.9 and 5.3, respectively).

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22321号 / 医博第4562号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 浅野 雅秀, 教授 岩田 想 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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<p>Providing wholesome pork products to consumers involves raising healthy pigs to grow well and be feed efficient from birth to market. Raising these pigs starts with ensuring the sow is healthy and provided good nutrition in gestation and lactation. Therefore, this dissertation primarily focuses on research of gut modifying feed additives fed to sows in gestation and lactation (and to their progeny in Chapter 3) to enhance reproductive performance and litter growth to weaning (and in the nursery). In Chapter 2, a total of 606 sows and their progeny were used to determine if feeding gestating and lactating sows a proprietary strain of Pichia guilliermondi as a whole-cell inactivated yeast product (WCY; CitriStim, ADM Animal Nutrition, Quincy, IL) improves sow and litter performance in a commercial production system. Sows were fed a control (CON) diet or control diet fortified with 0.15% of the WCY from d 35 of gestation through lactation. Sows supplemented with WCY in gestation and lactation had a greater number of total born piglets by 0.45 pigs (P < 0.04), piglets born alive (P < 0.04), heavier born alive litter weights (P < 0.001), and greater post cross-foster litter size (P < 0.001) compared to CON fed sows. Litter size at weaning was increased by 0.54 pigs when sows were fed WCY compared to CON (P < 0.001). However, litter weaning weights and 21-day adjusted litter weaning weights were similar (P > 0.158) with the 21-day adjusted litter weaning weights being numerically greater for the WCY sows. The average piglet weaning weights from CON fed sows were heavier by 0.35 kg compared to WCY (P < 0.001). This increase in body weight of piglets from CON fed sows is partially explained by their 0.93 days longer lactation (P < 0.001) and may also be due to the smaller litter size nursed throughout lactation. The percent of litters treated for scours decreased from 38.3% to 14.2% when sows were fed WCY (P < 0.001). The distribution of birth and weaning weights was not different (P > 0.2461) between treatments.</p><p>Chapter 3 encompasses a sow experiment where progeny were followed onto the nursery for a 28-d study. Forty-seven sows and their progeny were used to determine if feeding gestating and lactating sows a Bacillus licheniformis direct-fed microbial (DFM), an organic acid blend of medium and short-chain fatty acids (OA), or in combination improves sow lactation feed and water intake, litter growth, and subsequent reproductive performance. At weaning, offspring were fed a positive control diet (PC), negative control diet (NC), or a diet representative of their dam’s treatment to determine if there is an additive benefit to also feeding DFM and/or OA to nursery pigs in addition to their dams. On approximately d 80 of gestation, sows were fed one of four diets in a 2  2 factorial design: 1) gestation control (CON), 2) CON with DFM (1.6x109 CFU/kg of complete feed), 3) CON with 0.4% OA, 4) CON with both DFM and OA. Dietary treatments were also fed throughout lactation. Sows fed the OA diets had fewer mummies per litter (P < 0.010) compared to diets not containing OA. Sows fed diets with the DFM gave birth to lighter pigs born alive (1.5 vs. 1.7 kg; P < 0.003) compared to non-DFM fed sows, and a tendency for an interaction (P < 0.092) existed where feeding DFM+OA lessened the decrease in born alive BW. There was a tendency (P < 0.093) for pigs from DFM fed sows to also be lighter at weaning (5.8 vs. 6.2 kg) compared to pigs from sows not fed DFM, with no differences in litter sizes at weaning (P < 0.815). There was a tendency (P < 0.079) for the DFM to decrease the amount of sow BW loss in lactation compared to sows not fed the DFM (approximately 6 vs. 8% BW loss, respectively). The maintained BW in lactation was likely related to DFM sows numerically (P < 0.124) consuming 8.4% more feed during d 7-14 of lactation and 6.4% more feed (P < 0.234) from d 1 of lactation to weaning. The interaction was approaching a trend (P < 0.133) where sows fed DFM returned to estrus 1.0 day sooner than CON, but only 0.4 days sooner when sows were fed the DFM+OA diet.</p><p>Progeny weaned from these sows (n = 384, Initial BW = 6.15 kg) were blocked by initial BW and sex and allotted (6 pigs/pen, 8 pens/treatment) to one of 8 nursery treatments. Pigs from CON sows were fed a negative (NC; no antibiotics, no pharmacological Zn or Cu) or positive (PC; neomycin-oxytetracycline in phases 1 and 2 (827 and 551 ppm) and carbadox in phases 3 and 4 (55 ppm)) control diet. Pigs from sows fed DFM, OA, or DFM+OA were fed the NC diet or a diet representative of their dam’s treatment. Diets with DFM contained 1.6x109 CFU/kg of complete feed and diets with OA contained 0.5, 0.4, 0.3, and 0.0% OA in phases 1-4, respectively. Weaning weight was used as a covariate for nursery performance due to the DFM offspring being significantly lighter at weaning. For all phases and overall, PC fed pigs had greater ADG (P < 0.003) and ADFI (P < 0.059) than NC pigs. PC fed pigs had greater G:F (P < 0.010) than NC pigs for all phases and overall except d 21-28 (P < 0.532). Feeding DFM or OA in sow diets improved (interaction; P < 0.049) nursery pig G:F, but DFM+OA offspring had similar G:F compared to NC pigs from CON fed sows for d 7-14, 0-14, 0-21, and 0-28. Feeding DFM or OA to sows and their progeny decreased ADFI (interaction; P < 0.042) but improved G:F (interaction; P < 0.028) for d 7-14 and 0-14 with DFM+OA having similar performance to NC. For d 14-21 and 0-21, feeding DFM or OA to sows and their progeny decreased ADFI whereas DFM+OA increased ADFI above NC (interaction; P < 0.019). Overall, d 0-28, feeding DFM or OA to sows and their progeny improved G:F (interaction; P < 0.001) with DFM+OA having poorer G:F compared to NC. When the DFM was fed to sows and nursery pigs, progeny harvested on d 6 post-weaning had a decreased ratio of villus height to crypt depth (P < 0.035) compared to sows and pigs not consuming the DFM (average 1.34 vs. 1.67). Comparing pigs fed PC vs. NC from CON fed sows, expression of interleukin 10 (IL-10) was greater (0.51-fold increase; P < 0.046) for NC pigs than PC pigs. Expression of occludin (OCLN) was lower (P < 0.010) when OA was fed to the sows and pigs compared to when OA was not fed to the sows and pigs (0.78 vs. 1.00, respectively).</p><p>Chapter 4 is the only chapter that does not include maternal nutrition. In this chapter, maternal line gilts (Topigs Norsvin TN70) were bred with frozen semen from Duroc boars born from 2000 to 2017 divided into two genetic groups: semen from boars born in 2000 to 2005 and 2011 to 2017. These genetic groups had vastly different terminal sire indexes (TSI) of 88.2 and 112.0 for 2000 to 2005 and 2011 to 2017, respectively. A total of 155 pigs were weaned into 44 pens in a wean-to-finish facility to determine if genetics from two decades of sires and sex of the progeny impact progeny growth performance and carcass characteristics. The expected large growth performance differences indicated by the TSI’s of the two genetic groups were not observed. However, barrows had greater feed intake (P < 0.031) and fatter carcasses (P < 0.004) than the more feed efficient (P < 0.006) and leaner (P < 0.015) gilts in this study. Modern swine genetics have been selected to be leaner and results from this study agree, although the differences in live scan and carcass measurements were not as large as expected. The lack of differences between genetic groups could possibly be due to environmental differences including nutrition and rearing conditions from when these sires were alive compared to what was experienced by these progeny.</p><p>In conclusion, feeding gestating and lactating sows a proprietary strain of Pichia guilliermondi as a whole-cell inactivated yeast product increased the number of piglets born and weaned as well as decreased the prevalence of scours during lactation. Feeding a Bacillus licheniformis DFM to sows may decrease pig born alive weight and subsequent weaning weight but reduce sow BW loss through 6.4% more lactation feed intake, quickening the return to estrus. Other than decreasing the number of mummies per litter, feeding the OA alone or in combination did not improve sow reproductive or litter growth performance in this study. Feeding DFM or OA to sows or their offspring may improve nursery feed efficiency but did not result in a difference in ADG or final BW in this study. Feeding the combination diet (DFM+OA) to the sow and nursery pigs tended to increase ADFI. Feeding antibiotics post-weaning continued to improve pig growth performance resulting in 2.7 kg heavier pigs at the end of the 28-d nursery period. Lastly, the expected large growth performance differences indicated by the TSI’s of two genetic groups created by using frozen semen from boars born in 2000 to 2005 and 2011 to 2017 were not observed.</p>