Prior work by our research group showed that the total Western diet (TWD), a rodent diet which models the typical American diet, promoted the development of colon tumors when fed to mice. Other researchers previously showed that vancomycin, an antibiotic that changes the gut microbiome composition, causes differential changes in the severity of colon inflammation and CRC. Our goal was to determine the combined effects of feeding the TWD and vancomycin treatment on colitis and CRC, and if these factors interact. We hypothesized that vancomycin treatment would mitigate colitis and CRC in mice fed the TWD. To this end, mice were fed either a healthy diet or the TWD. Mice were also given either vancomycin in their drinking water, or plain water. Colon inflammation and tumor development was induced in mice by treating them with a gut irritant and a chemical carcinogen. Contrary to our hypothesis, mice fed the TWD and treated with vancomycin experienced more severe intestinal inflammation and had greater tumor burden compared to mice fed a standard diet. Furthermore, vancomycin treatment decreased the number of bacteria l species present in the fecal microbiome and altered the relative abundance of the taxa that were present. Rather than the diet consumed, vancomycin was the driving force in determining the bacterial community composition. Overall, these results suggest that vancomycin-induced changes to the gut microbiome may be associated with increased development of colon tumors, particularly in the context of a Western dietary pattern.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-28T14:51:26Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO - FICHA CATALOGRÁFICA - Tamires Meira Menezes - IMPRESSAO definitivo 20 de maio def.pdf: 2274072 bytes, checksum: e16a0eba082be492ae84d83288410672 (MD5) / Made available in DSpace on 2016-07-28T14:51:26Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO - FICHA CATALOGRÁFICA - Tamires Meira Menezes - IMPRESSAO definitivo 20 de maio def.pdf: 2274072 bytes, checksum: e16a0eba082be492ae84d83288410672 (MD5) Previous issue date: 2016-02-25 / CAPEs / Estudos epidemiológicos evidenciam que a obesidade durante a gestação prejudica o desenvolvimento fetal e predispõe a prole a maior incidência de doenças crônicas não transmissíveis (DCNT) frequentemente coexistentes com processos inflamatórios. Dessa forma, este estudo tem como objetivo avaliar a fase aguda da resposta inflamatória e a eficácia farmacológica da nimesulida na prole adulta de ratos Wistar alimentados com uma Dieta Ocidentalizada durante a gestação e lactação. A partir do 1º dia de gestação, as matrizes foram divididas aleatoriamente em dois grupos: 1) DPgl – que permaneceram recebendo a DP de biotério (Presence ®) durante a gestação e lactação e 2) DOgl que passaram a receber DO durante a gestação e lactação. Em seguida, segundo a manipulação nutricional, as proles foram divididas em quatro grupos: i) DPgl-DP - prole das matrizes que receberam a DP durante a gestação e lactação e permaneceram com a mesma no pós-desmame até o 60º dia de vida; ii) DOgl-DO - prole de matrizes que receberam a DO durante a gestação e lactação e permaneceram com a mesma no pós-desmame até o 60º dia de vida; DPgl-DO - prole de matrizes que receberam DP durante a gestação e lactação, mas que passaram a consumir DO no pós-desmame até o 60º dia de vida e iv) DOgl-DP - prole das matrizes que receberam DO durante a gestação e lactação, mas que passaram a receber DP no pós-desmame até o 60º dia de vida. Nesse experimento os animais receberam Carragenina (0,1 mL, 1% w/v) na região subplantar da pata esquerda traseira para avaliar a resposta inflamatória aguda da prole e o efeito anti-inflamatório da nimesulida. No modelo de inflamação aguda nos intervalos de 120, 180 e 240 min, respectivamente, o grupo DOgl–DO (1,66 ± 0,61*; 2,06 ± 0,62* e 2,10 ± 0,67*) e o grupo DOgl–DP (1,62 ± 0,16*; 1,92 ± 0,36* e 1,51 ± 0,37*) exibiram aumento significativo (p<0,05) em relação ao DPgl–DP (0,93 ± 0,20; 1,11 ± 0,26 e 1,07±0,14). Enquanto o DPgl–DO (1,35 ± 0,16* e 1,55 ± 0,23*) só apresentou diferença (p<0,05) comparada ao DPgl–DP nos intervalos de 120 e 180 min, respectivamente. A atividade anti-edematogênica da nimesulida no grupo DPgl-DPn, foi observada nos intervalos de 120, 180 e 240 min; enquanto no grupo DOgl-DOn esse efeito foi observado apenas no intervalo de 120 min após a injeção subplantar da carragenina. Quando comparados a seus respectivos grupos controle tratados com carboximetilcelulose (DOgl-DOc versus DOgl-DOn ou DPgl-DPc versus DPgl-DPn), o efeito anti-edematogênico da nimesulida, expresso em percentual de inibição do edema, medido nos intervalos de 180 (33,98%) e 240 minutos (33,80%), após a injeção do agente edematogênico, foi significativamente (p<0,05) menor em relação ao grupo DPgl-DPn (38,73% e 38,31%, respectivamente). A partir dos dados concluímos que, a dieta ocidentalizada acentuou a intensidade da resposta inflamatória aguda e reduziu o efeito da nimesulida sobre o edema de pata induzido por carragenina em ratos Wistar. / Epidemiological studies show that obesity during pregnancy affect fetal development and predispose the offspring to higher incidence of chronic noncommunicable diseases (NCDs) often coexisting with inflammatory processes. Thus, this study aims to evaluate the acute phase of the inflammatory response and the pharmacological efficacy of nimesulide in the adult offspring of Wistar rats fed a Westernized diet during pregnancy and lactation. From the 1st day of pregnancy, the mothers were randomly divided into two groups: 1) SDgl - that were fed the SD vivarium (Presence ®) during pregnancy and lactation and 2) WDgl that have received WD during pregnancy and lactation. Then, according to nutritional manipulation, the proles were divided into four groups: i) SDgl-SD - offspring of mothers who received SD during pregnancy and lactation and kept the same post-weaning until 60 days of life; ii) WDgl-WD - offspring of mothers who received the WD during pregnancy and lactation and kept the same post-weaning until 60 days of life; SDgl-WD - offspring of mothers who received SD during pregnancy and lactation, but that began to consume WD post-weaning until the 60th day of life and iv) WDgl-SD - offspring of mothers who received WD during pregnancy and lactation but have received SD post-weaning until the 60th day of life. In this experiment the animals received carrageenan (0.1ml of 1% w / v) in the subplantar region of the left hind paw to assess acute inflammatory response of offspring and anti-inflammatory effect of nimesulide. In the model of acute inflammation in the intervals 120, 180 and 240 min, respectively, WDgl-WD group (1.66 ± 0.61 *; 2.06 * ± 0.62 and 2.10 ± 0.67 *) and WDgl-SD group (1.62 ± 0.16 *; 1.92 * ± 0.36 and 1.51 ± 0.37 *) showed a significant increase (p <0.05) compared to SDgl-SD (0.93 ± 0.20, 1.11 ± 0.26 and 1.07 ± 0.14). While SDgl-WD (1.35 ± 0.16 and 1.55 ± 0.23 * *), the only difference (p <0.05) compared to SDgl-SD in the intervals 120 and 180 min, respectively. The anti-edema activity of nimesulide in SDgl-SDn group was observed at intervals of 120, 180 and 240 min; while in WDgl-WDn group this effect was only observed in the range of 120 min after subplantar injection of carrageenan. When compared to their respective control groups treated with carboxymethylcellulose (WDgl-WD vs. WDgl-WDn or SDgl-SD versus SDgl-SDn), anti-oedematogenic effect of nimesulide expressed as percentage inhibition of edema measured at the intervals of 180 ( 33.98%) and 240 minutes (33.80%), after injection of oedematogenic agent, was significantly (p <0.05) lower in relation to SDgl-SDn group (38.73% and 38.31%, respectively). From the data we conclude that the westernized diet accentuated the intensity of the acute inflammatory response and reduce the effect of nimesulide on the paw edema induced by carrageenan in rats.

Thesis (Master of Environmental Health)--Cape Peninsula University of Technology, 2020 / Background: The development of metabolic disease is accompanied by changes in gut microbiota phenotype, including a decrease of beneficial bacteria and increase of pernicious bacteria of the gastrointestinal tract. A Western (high-fat and high-sugar) diet, sedentary lifestyle and altered gut microbiota diversity have been associated with an increased risk of developing metabolic diseases such as type 2 diabetes and its associated risk factor, obesity. Many researchers have studied the link between the gut microbiota and diet. Hence our in vitro study is aimed at investigating the potential prebiotic effect of an aspalathin-rich unfermented rooibos extract, Afriplex GRT™ and aspalathin on the faecal bacterial diversity of vervet monkeys fed Western diet. Methodology: A total of six vervet monkeys (Chlorocebus pygerythrus) were selected from monkeys fed either a maize based normal diet (standard diet group; n=3) or a high fat diet (Western diet group; n=3) for more than 5-years. Faecal samples were collected from the animals in both groups at the Primate Unit and Delft Animal Centre (PUDAC) between 7 – 9 AM. Faecal samples from the two groups were divided into culture-independent baseline samples (before culture) and culture-dependent samples (after anaerobic culture). The culture-dependent samples were cultured under anaerobic conditions at 37°C for 10 hours, with or without Afriplex GRT™ extract or aspalathin. Bacterial genomic DNA (gDNA) was extracted from all samples using the NucleoSpin® DNA Stool extraction kit. Purified gDNA was sent for metagenomic sequencing for 16S rRNA gene analysis of microbial diversity using an Ion Torrent Next-generation Sequencing platform. Results: Results indicated that the Western diet affects the abundance of several bacterial species. Afriplex GRT™ and aspalathin significantly enhanced the relative abundance of health promoting butyrate-producing bacteria such as Faecalibacterium prausnitzii in both standard and Western diet groups (p= 0.02 and p=0.04, respectively). A similar trend was observed in other beneficial bacteria such as Eubacterium spp., Sutterella spp., and Dorea longicatena. Conclusion: Based on the data observed, it can be suggested that Afriplex GRT™ has a beneficial prebiotic effect on gut microbiota diversity and gut health.

La stéatose hépatique non alcoolique (NAFLD) est une manifestation du syndrome métabolique dont la prévalence est en constante évolution. Les stratégies thérapeutiques sont soit difficiles à mettre en œuvre soit d’une efficacité limitée. Nous avons étudié une approche nutritionnelle avec 3 acides aminés particuliers : la glutamine, l’arginine et la citrulline (Cit) pour leurs propriétés de pharmaconutriments azotés. Dans un modèle de NAFLD modérée induite par le fructose, seule la citrulline (1 g/kg/j) permettait une amélioration du métabolisme lipidique. Toutefois, l’étude de la cinétique de NAFLD suggérait un effet protecteur du simple apport azoté. L’effet spécifique de la Cit par rapport au simple apport azoté (AANE) a donc été déterminé dans un modèle de NAFLD induite par 8 semaines de régime enrichi en fructose. Ceci a permis de confirmer l’effet protecteur de la Cit et des AANE. Toutefois, la Cit exerce un effet plus spécifique sur l’expression de Srebp1c et de Fas et améliore la disponibilité périphérique en Arg, un élément important de l’insulino-sensibilité. La stéatose est associée à une perte de masse maigre, suggérant une oxydation des AA aux dépens de l’anabolisme musculaire, et une accumulation de lipides à l’origine de la stéatose et du gain de masse grasse viscérale ; la Cit et les AANE en agissant sur la NAFLD préviendraient cet effet du fructose. Nous avons ensuite évalué les effets de la Cit dans un modèle de stéatose plus sévère induite par le western diet. La Cit améliore la fonction hépatique (diminution des lipides et de l’inflammation hépatique) et préserve l’axe intestin-foie (restauration du groupe Bacteroides/Prevotella dans la muqueuse colique, diminution de l’inflammation intestinale et augmentation de l’expression de la Claudine 1) mais ne permet pas de prévenir l’ensemble des altérations liées au western diet. Il serait intéressant d’évaluer la relation effet/dose et l’efficacité de la Cit en association avec d’autres traitements. Par ailleurs, les mécanismes cellulaires restent à élucider. / Nonalcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome whose prevalence is constantly growing. Therapeutic strategies are either difficult to implement or of limited effectiveness. We studied a nutritional approach with three specific amino acids: glutamine, arginine and citrulline (Cit) for their pharmaconutrient properties. In a model of moderate fructose-induced NAFLD, citrulline alone (1 g/kg/day) improved lipid metabolism. However, the study of the kinetics of NAFLD suggested a protective effect of nitrogen supply by itself. The specific effect of Cit compared to that of nitrogen (NEAAs) has been determined in a model of 8 week fructose diet-induced NAFLD. This has confirmed the protective effect of Cit and NEAAs. However, Cit exerted a specific effect on the expression of Fas and SREBP1c and improves peripheral Arg availability, an important component of insulin sensitivity. Steatosis was associated with loss of lean mass, suggesting AA oxidation at the expense of muscle anabolism, and lipid accumulation causing steatosis and visceral fat gain; Cit and NEAAs by acting on NAFLD would prevent this effect of fructose. We then evaluated the effects of Cit in a model of more severe steatosis induced by western diet. Cit improved liver function (reduced fat and liver inflammation) and protected the liver-gut axis (restoration of Bacteroides/Prevotella group in the colonic mucosa, decreased intestinal inflammation and increased expression of claudin 1) but did not prevent all western diet-induced alterations. It would be interesting to assess the dose/effect relationship and the effectiveness of Cit in combination with other treatments. Furthermore, the cellular mechanisms remain to be elucidated.

No description available.

The present thesis investigated the effects of a western diet (WD) on cell death and functional outcome following global ischemia in rats. Experiment 1 assessed the effects of a 60-day WD regimen on temperature, activity and glucose levels in normal rats. Experiment 2 evaluated the influence of a 60-day WD regimen on hippocampal CA1 injury and cognition following global ischemia. Results from experiment 1 revealed significant differences in activity levels only; animals fed the WD were less active than control diet animals. Results from experiment 2 suggested that a WD did not aggravate CA1 injury or behavioral deficits. The second portion of my thesis examined the effects of a 120-day WD regimen on stroke severity and cognition following global ischemia. Briefly, the surgical protocol used to induce a global ischemic insult did not produce consistent damage across all animals. Plausible reasons for this surgical variability and future directions are discussed.

Insulin resistance and obesity are major public health concerns. The impact of diet and genetics on insulin resistance and obesity is well accepted. Additionally, the gut microbiota has been shown to influence obesity and metabolic disorders. However, much remains to be understood about the role of gut microbiota in the development of insulin resistance and obesity. We utilized a mouse model lacking PAS kinase, a protein involved in cellular metabolism, in order to better understand the relationship between diet, genetics and the gut microbiota. Previous research has shown that mice lacking PAS kinase were protected from the effects of a high fat diet, gaining less weight and showing a better response to insulin. Surprisingly, when PAS-kinase deficient mice were placed on a western-style, high fat, high sugar (HFHS) diet, they became obese and had an impaired response to insulin, much like wild type mice on the same diet. Mutant mice did, however, show more resistance to the effects of the unhealthy diet in one aspect-they maintained normal levels of claudin-1 in the colon, suggesting that they were less likely to develop excessive gut permeability (leaky gut). While significant differences in gut microbial composition were seen in response to the HFHS diet, with shifts in the ratio of Firmicutes/Bacteroidetes and increases in the levels of Actinobacteria, none of the differences correlated with genotype. Unexpectedly, however, within the mice on the HFHS diet and regardless of genotype, the composition of the gut microbiota diverged into two clusters. The mice in one cluster showed more resistance to obesity and their glucose response was like that of wild type mice on a healthy normal chow diet (NCD), while mice in the other cluster showed more weight gain and impaired glucose response. No similar gut microbiota divergence occurred in mice on the NCD, suggesting that the HFHS diet made mice vulnerable to (but did not cause) the development of a harmful gut microbiota, whereas the healthy NCD protected against spontaneous harmful shifts in the composition of the gut microbiota.

The Western diet is commonly consumed by industrialized societies and characterized by an increased consumption of vegetable oils rich in omega-6 (n-6) fatty acids. This results in a higher ratio of omega-6 to omega-3 (n-3) fatty acids in the diet. Omega-6 polyunsaturated fatty acids (PUFA) are believed to induce a pro-inflammatory response in the body. Therefore, this change in PUFA concentration and/or ratio of n-6:n-3 in the Western diet may contribute to colorectal cancer (CRC) risk. Five identical diets, varying only in PUFA concentration and n-6:n-3 ratio, were fed to mice dosed with a carcinogen and an inflammatory accent (AOM+DSS). The diets included: 1.) AIN-93G, control diet, containing 7% (kcal) dietary PUFA, 7:1 n-6:n-3 ratio, 2.) 2.5% dietary PUFA 1:1 n-6:n-3 ratio, 3.) 2.5% PUFA 20:1 n-6:n-3, 4.) 10% PUFA 1:1 n-6:n-3, and 5.) 10% PUFA 20:1 n-6:n-3. PUFA ratio had a significant effect on tumor size. Diets having an n-6:n-3 ratio of 1:1 resulted in significantly larger tumors than diets with an n-6:n-3ratio of 20:1. Mice fed either the AIN-93G or 2.5% 1:1 diet had the highest number of tumors compared to the other experimental diets. From these results, it appears that the dietary PUFA profile influences the etiology of CRC. Studies investigating CRC commonly use rodent models to investigate human diseases. Typically rodents are fed diets formulated to promote growth and heath, however these diets are considerably different than the Western diet in terms of macro- and micronutrients. Diet is known to influence CRC incidence, which led to the development of the Total Western Diet (TWD) by Hinze and colleagues. The TWD is a rodent diet that uses purified ingredients to match the macro- and micronutrient composition of the average American diet. However, the complex nature of whole-foods is also known to impact colon health, so the TWD was redesigned. The TWD-2 is the only whole-foods-based rodent diet that emulates the macro- and micronutrient consumption of the average American. Initiating studies using the TWD-2, in place of the AIN diets, will hopefully make the rodent a better model for human disease research.

The composition of the gut microbiome can be affected by environmental factors, such as diet. The Western dietary pattern is associated with microbiome dysbiosis and adverse health outcomes, including obesity and metabolic disorders. The objective of this study was to examine the effect of gut microbiota from lean or obese human donors on metabolism and weight gain in recipient mice fed one of three basal diets: 1) the standard AIN93G diet, which promotes rodent health; 2) the total Western diet (TWD), which mimics the American dietary pattern and promotes inflammation-associated colorectal carcinogenesis; and 3) a 45% high fat diet-induced obesity (DIO) diet, which promotes excessive weight gain and symptoms of metabolic syndrome. We hypothesized that fecal microbiome transfer (FMT)from obese human donors would lead to an obese phenotype with symptoms of metabolic syndrome in recipient mice, and that consumption of TWD or DIO diets would further exacerbate the metabolic syndrome phenotype. The experiment design consisted of two main factors: body type of the human donor (obese or lean) and experimental diet (AIN, DIO or TWD), which was fed to mice for 22 weeks. Prior to FMT, the resident gut microbiome in mice was depleted using an established broad spectrum antibiotic/antifugal oral dosing regimen. Interestingly, human donor body type did not significantly affect final body weight or body composition in recipient

No description available.