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1.
Food Funct ; 15(6): 3141-3157, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38439638

ABSTRACT

Four major types of resistant starch (RS1-4) are present in foods, all of which can alter the microbiome and are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs). Type 4 RSs are chemically modified starches, not normally found in foods, but have become a popular food additive as their addition increases fiber content. Multiple studies, in humans and rodents, have explored how different RS4 affect post-prandial glucose metabolism, but fewer studies have examined the effects of RS4 consumption on the microbiome. In addition, many RS studies conducted in rodents use high-fat diets that do not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data that mimics the macro and micronutrient composition of a typical American diet, for six weeks, and then supplemented with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch, for an additional three weeks. The cecal contents were analyzed for SCFA content and microbiota composition. Butyrate production was increased while branched chain SCFA production decreased. The alpha-diversity of the microbiome decreased in mice fed the TWD with 10% VF 1490 added while the beta-diversity plot showed that the 5% and 10% VF groups were distinct from mice fed the TWD. Similarly, the largest changes in relative abundance of various genera were greatest in mice fed the 10% VF diet. To examine the effect of VF consumption on tissue gene expression, cecal and distal colon tissue mRNA abundance were analyzed by RNASeq. Gene expression changes were more prevalent in the cecum than the colon and in mice fed the 10% VF diet, but the number of changes was substantially lower than we previously observed in mice fed the TWD supplemented with native potato starch (RPS). These results provide additional evidence that the structure of the RS is a major factor determining its effects on the microbiome and gene expression in the cecum and colon.


Subject(s)
Cecum , Resistant Starch , Solanum tuberosum , Animals , Mice , Cecum/metabolism , Cecum/microbiology , Diet, Western , Gene Expression , Microbiota , Nutrition Surveys , Resistant Starch/metabolism , Solanum tuberosum/chemistry
2.
Neuroscience ; 544: 88-101, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38431042

ABSTRACT

Short-chain fatty acids (SCFAs) are bioactive lipids that are released into the colon as a metabolite of bacterial fermentation of dietary fibers. Beyond their function in the gastrointestinal tract, SCFAs can also have effects inthe brain, as a part of the gut-brain axis. Recent investigations into potential therapeutic interventions via the manipulation of the gut microbiome-and thus their SCFA metabolites-has been emerging as a new branch of personalized medicine,especially for mental health conditions. The current study sought to measure and localize SCFA receptors in the mouse brain. Two cell types have been implicated in the gut-brain axis: microglia and serotonergic neurons. We used fluorescentin situhybridization in brain sections from mice fed diets with different compositions of fat and fiber to quantify the mRNA levels of known gene markers of these two cell types and colocalize each with mRNA for free fatty acid receptors that bind SCFAs. We focused onmicroglia in the hippocampus and the serotonergic neurons of the dorsal raphe. We found high colocalization of SCFA receptors in both microglia and serotonergic neurons and discovered that SCFA receptor expression in the dorsal raphe is driven by fiber solubility, while SCFA receptor expression in the hippocampus is driven by fiber amount. Higher dietary fiber was associated with decreased tyrosine hydroxylase expression. Thus, our results indicate that the amount and solubility of dietary fiber can change gene expression in the brain's microglia and serotonin neurons, potentially via sensitivity to circulating levels of SCFAs produced in the gut.


Subject(s)
Microglia , Serotonergic Neurons , Animals , Mice , Microglia/metabolism , Serotonergic Neurons/metabolism , Fatty Acids, Volatile/metabolism , Dietary Fiber/metabolism , Brain/metabolism
3.
J Dairy Sci ; 107(2): 902-916, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37776997

ABSTRACT

The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent interest in the dietary fatty acid profile to dairy cows enlightened the possible beneficial effect of specific fatty acids (e.g., palmitic, stearic, and oleic acids) on total-tract fiber digestibility. Because palmitic, stearic, and oleic acids are the main fatty acids present in ruminal bacterial cells, we hypothesize that the dietary supply of these fatty acids will favor their incorporation into the bacterial cell membranes, which will support the growth and enrichment of fiber-digesting bacteria in the rumen. Our objective in this experiment was to investigate how dietary supply of palmitic, stearic, and oleic acid affect fiber digestion, bacterial membrane fatty acid profile, microbial growth, and composition of the rumen bacterial community. Diets were randomly assigned to 8 single-flow continuous culture fermenters arranged in a replicated 4 × 4 Latin square with four 11-d experimental periods. Treatments were (1) a control basal diet without supplemental fatty acids (CON); (2) the control diet plus palmitic acid (PA); (3) the control diet plus stearic acid (SA); and (4) the control diet plus oleic acid (OA). All fatty acid treatments were included in the diet at 1.5% of the diet (dry matter [DM] basis). The basal diet contained 50% orchardgrass hay and 50% concentrate (DM basis) and was supplied at a rate of 60 g of DM/d in 2 equal daily offers (0800 and 1600 h). Data were analyzed using a mixed model considering treatments as fixed effect and period and fermenter as random effects. Our results indicate that PA increased in vitro fiber digestibility by 6 percentage units compared with the CON, while SA had no effect and OA decreased fiber digestibility by 8 percentage units. Oleic acid decreased protein expression of the enzymes acetyl-CoA carboxylase compared with CON and PA, while fatty acid synthase was reduced by PA, SA, and OA. We observed that PA, but not SA or OA, altered the bacterial community composition by enhancing bacterial groups responsible for fiber digestion. Although the dietary fatty acids did not affect the total lipid content and the phospholipid fraction in the bacterial cell, PA increased the flow of anteiso C13:0 and anteiso C15:0 in the phospholipidic membrane compared to the other treatments. In addition, OA increased the flow of C18:1 cis-9 and decreased C18:2 cis-9,cis-12 in the bacterial phospholipidic membranes compared to the other treatments. Palmitic acid tended to increase bacterial growth compared to other treatments, whereas SA and OA did not affect bacterial growth compared with CON. To our knowledge, this is the first research providing evidence that palmitic acid supports ruminal fiber digestion through shifts in bacterial fatty acid metabolism that result in changes in growth and abundance of fiber-degrading bacteria in the microbial community.


Subject(s)
Dietary Supplements , Oleic Acid , Cattle , Female , Animals , Oleic Acid/metabolism , Milk/metabolism , Lactation , Rumen/metabolism , Digestion , Fatty Acids/metabolism , Diet/veterinary , Palmitic Acid/metabolism
4.
J Anim Sci Biotechnol ; 14(1): 49, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37004100

ABSTRACT

BACKGROUND: With rising concerns regarding the effects of red meat on human and environmental health, a growing number of livestock producers are exploring ways to improve production systems. A promising avenue includes agro-ecological practices such as rotational grazing of locally adapted ruminants. Additionally, growing consumer interest in pasture-finished meat (i.e., grass-fed) has raised questions about its nutritional composition. Thus, the goal of this study was to determine the impact of two common finishing systems in North American bison-pasture-finished or pen-finished on concentrates for 146 d-on metabolomic, lipidomic, and fatty acid profiles of striploins (M. longissimus lumborum). RESULTS: Six hundred and seventy-one (671) out of 1570 profiled compounds (43%) differed between pasture- and pen-finished conditions (n = 20 animals per group) (all, P < 0.05). Relative to pasture-finished animals, the muscle of pen-finished animals displayed elevated glucose metabolites (~ 1.6-fold), triglycerides (~ 2-fold), markers of oxidative stress (~ 1.5-fold), and proteolysis (~ 1.2-fold). In contrast, pasture-finished animals displayed improved mitochondrial (~ 1.3-fold higher levels of various Krebs cycle metabolites) and carnitine metabolism (~ 3-fold higher levels of long-chain acyl carnitines) (all P < 0.05). Pasture-finishing also concentrated higher levels of phenolics (~ 2.3-fold), alpha-tocopherol (~ 5.8-fold), carotene (~ 2.0-fold), and very long-chain fatty acids (~ 1.3-fold) in their meat, while having lower levels of a common advanced lipoxidation (4-hydroxy-nonenal-glutathione; ~ 2-fold) and glycation end-product (N6-carboxymethyllysine; ~ 1.7-fold) (all P < 0.05). In contrast, vitamins B5, B6, and C, gamma/beta-tocopherol, and three phenolics commonly found in alfalfa were ~ 2.5-fold higher in pen-finished animals (all P < 0.05); suggesting some concentrate feeding, or grazing plants rich in those compounds, may be beneficial. CONCLUSIONS: Pasture-finishing (i.e., grass-fed) broadly improves bison metabolic health and accumulates additional potential health-promoting compounds in their meat compared to concentrate finishing in confinement (i.e., pen-finished). Our data, however, does not indicate that meat from pen-finished bison is therefore unhealthy. The studied bison meat-irrespective of finishing practice-contained favorable omega 6:3 ratios (< 3.2), and amino acid and vitamin profiles. Our study represents one of the deepest meat profiling studies to date (> 1500 unique compounds), having revealed previously unrecognized differences in animal metabolic health and nutritional composition because of finishing mode. Whether observed nutritional differences have an appreciable effect on human health remains to be determined.

5.
Nutrients ; 14(24)2022 Dec 10.
Article in English | MEDLINE | ID: mdl-36558431

ABSTRACT

Black raspberries (BRB) are rich in anthocyanins with purported anti-inflammatory properties. However, it is not known whether dietary supplementation would ameliorate Western-diet enhanced gut inflammation and colon tumorigenesis. We employed a mouse model of colitis-associated colorectal cancer (CAC) to determine the effects of dietary supplementation with 5 to 10% (w/w) whole, freeze-dried BRB in male C57BL/6J mice fed either a standard healthy diet (AIN93G) or the total Western diet (TWD). In a pilot study, BRB suppressed colitis and colon tumorigenesis while also shifting the composition of the fecal microbiome in favor of taxa with purported health benefits, including Bifidobacterium pseudolongum. In a follow-up experiment using a 2 × 2 factorial design with AIN and TWD basal diets with and without 10% (w/w) BRB, supplementation with BRB reduced tumor multiplicity and increased colon length, irrespective of the basal diet, but it did not apparently affect colitis symptoms, colon inflammation or mucosal injury based on histopathological findings. However, BRB intake increased alpha diversity, altered beta diversity and changed the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others, of the fecal microbiome. Notably, changes in microbiome profiles were inconsistent with respect to the basal diet consumed. Overall, these studies provide equivocal evidence for in vivo anti-inflammatory effects of BRB on colitis and colon tumorigenesis; yet, BRB supplementation led to dynamic changes in the fecal microbiome composition over the course of disease development.


Subject(s)
Colitis-Associated Neoplasms , Colitis , Gastrointestinal Microbiome , Rubus , Male , Mice , Animals , Diet, Western , Anthocyanins/pharmacology , Pilot Projects , Mice, Inbred C57BL , Colitis/complications , Colon , Inflammation , Carcinogenesis , Cell Transformation, Neoplastic , Anti-Inflammatory Agents/pharmacology , Dietary Supplements , Disease Models, Animal
6.
Front Cell Dev Biol ; 10: 947444, 2022.
Article in English | MEDLINE | ID: mdl-36238688

ABSTRACT

Septate junctions (SJs) serve as occluding barriers in invertebrate epithelia. In Drosophila, at least 30 genes are required for the formation or maintenance of SJs. Interestingly, loss-of-function mutations in core SJ components are embryonic lethal, with defects in developmental events such as head involution and dorsal closure (DC) that occur prior to the formation of a mature SJ, indicating a role for these proteins in mid-embryogenesis independent of their occluding function. To understand this novel function in development, we examined loss-of-function mutations in three core SJ proteins during the process of DC. DC occurs during mid-embryogenesis to seal a dorsal gap in the epidermis following germ band retraction. Closure is driven by contraction of the extraembryonic amnioserosa cells that temporarily cover the dorsal surface and by cell shape changes (elongation) of lateral epidermal cells that bring the contralateral sheets together at the dorsal midline. Using live imaging and examination of fixed tissues, we show that early events in DC occur normally in SJ mutant embryos, but during later closure, coracle, Macroglobulin complement-related and Neurexin-IV mutant embryos exhibit slower rates of closure and display aberrant cells shapes in the dorsolateral epidermis, including dorsoventral length and apical surface area. SJ mutant embryos also show mild defects in actomyosin structures along the leading edge, but laser cutting experiments suggest similar tension and viscoelastic properties in SJ mutant versus wild type epidermis. In a high percentage of SJ mutant embryos, the epidermis tears free from the amnioserosa near the end of DC and live imaging and immunostaining reveal reduced levels of E-cadherin, suggesting that defective adhesion may be responsible for these tears. Supporting this notion, reducing E-cadherin by half significantly enhances the penetrance of DC defects in coracle mutant embryos.

8.
Animals (Basel) ; 12(8)2022 Apr 14.
Article in English | MEDLINE | ID: mdl-35454263

ABSTRACT

Fall- or spring-born steers grazed monoculture irrigated birdsfoot trefoil (BFT; Lotus corniculatus L.) or cicer milkvetch (CMV; Astragalus cicer L.) pastures for approximately 12 weeks for 3 years and were compared with steers on concentrate diets. In the 3rd year, an irrigated meadow bromegrass (MBG; Bromus biebersteinii Roem. and Schult.) pasture treatment was added for further comparison. Steer average daily gain (ADG) was 1.31, 0.94, 0.83 and 0.69 kg d−1 on concentrate, 'Norcen' BFT, 'Oberhaunstadter' BFT, and 'Monarch' CMV diets, respectively; ADG on grass pastures was 0.43 kg d−1. The ADG on the concentrate diet was greater than ADG on legume or grass pastures, ADG was greater on BFT than CMV in every year (p < 0.03), and ADG on BFT was greater than ADG on grass (p < 0.03). The rate constant of gas production of an in vitro rumen fermentation demonstrated a slower rate of microbial digestion for CMV than for BFT. The elevated ADG on BFT pastures may be due to greater non-fiber carbohydrate (NFC) concentration and reduced neutral detergent fiber (NDF) concentration combined with condensed tannins that protect proteins in the rumen but do not impede protein digestion in the abomasum and intestines.

9.
Bioprocess Biosyst Eng ; 45(1): 217-226, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34657162

ABSTRACT

Polypropylene was modified to contain chitosan and evaluate its ability to generate Lactobacillus casei biofilms and their lactic acid production. Biofilm formation was carried out in either rich or minimal media. The chitosan-modified polypropylene harbored ~ 37% more cells than the control polypropylene. The biofilms from the chitosan-modified polypropylene grown in rich medium produced ~ 2 times more lactic acid after 72 h of incubation than the control suspended cells. There was no significant difference in the production of lactic acid after 72 h by L. casei biofilms on the chitosan-modified polypropylene grown in minimal media as compared with cells in suspension after 48 h and 72 h of incubation. Infrared spectroscopy confirmed higher deposition of nutrients and biomass on the chitosan-modified polypropylene as compared to the chitosan-free polypropylene. Electron and atomic force microscopy confirmed thicker biofilms when rich media were used to grow them as compared to minimal medium.


Subject(s)
Lactic Acid/metabolism , Lactobacillus/metabolism , Biofilms
10.
Integr Comp Biol ; 61(6): 2233-2243, 2022 02 05.
Article in English | MEDLINE | ID: mdl-33970251

ABSTRACT

The rapid expansion of genome sequence data is increasing the discovery of protein-coding genes across all domains of life. Annotating these genes with reliable functional information is necessary to understand evolution, to define the full biochemical space accessed by nature, and to identify target genes for biotechnology improvements. The majority of proteins are annotated based on sequence conservation with no specific biological, biochemical, genetic, or cellular function identified. Recent technical advances throughout the biological sciences enable experimental research on these understudied protein-coding genes in a broader collection of species. However, scientists have incentives and biases to continue focusing on well documented genes within their preferred model organism. This perspective suggests a research model that seeks to break historic silos of research bias by enabling interdisciplinary teams to accelerate biological functional annotation. We propose an initiative to develop coordinated projects of collaborating evolutionary biologists, cell biologists, geneticists, and biochemists that will focus on subsets of target genes in multiple model organisms. Concurrent analysis in multiple organisms takes advantage of evolutionary divergence and selection, which causes individual species to be better suited as experimental models for specific genes. Most importantly, multisystem approaches would encourage transdisciplinary critical thinking and hypothesis testing that is inherently slow in current biological research.


Subject(s)
Genome , Animals
11.
Nutrients ; 13(12)2021 Dec 16.
Article in English | MEDLINE | ID: mdl-34960062

ABSTRACT

Excess vitamin intake during pregnancy leads to obesogenic phenotypes, and folic acid accounts for many of these effects in male, but not in female, offspring. These outcomes may be modulated by another methyl nutrient choline and attributed to the gut microbiota. Pregnant Wistar rats were fed an AIN-93G diet with recommended vitamin (RV), high 10-fold multivitamin (HV), high 10-fold folic acid with recommended choline (HFol) or high 10-fold folic acid without choline (HFol-C) content. Male and female offspring were weaned to a high-fat RV diet for 12 weeks post-weaning. Removing choline from the HFol gestational diet resulted in obesogenic phenotypes that resembled more closely to HV in male and female offspring with higher body weight, food intake, glucose response to a glucose load and body fat percentage with altered activity, concentrations of short-chain fatty acids and gut microbiota composition. Gestational diet and sex of the offspring predicted the gut microbiota differences. Differentially abundant microbes may be important contributors to obesogenic outcomes across diet and sex. In conclusion, a gestational diet high in vitamins or imbalanced folic acid and choline content contributes to the gut microbiota alterations consistent with the obesogenic phenotypes of in male and female offspring.


Subject(s)
Diet/adverse effects , Gastrointestinal Microbiome , Maternal Nutritional Physiological Phenomena , Obesity/etiology , Prenatal Exposure Delayed Effects/etiology , Animal Nutritional Physiological Phenomena , Animals , Animals, Newborn , Choline/adverse effects , Diet/methods , Female , Folic Acid/adverse effects , Male , Pregnancy , Rats , Rats, Wistar , Vitamins/adverse effects
12.
G3 (Bethesda) ; 11(7)2021 07 14.
Article in English | MEDLINE | ID: mdl-33871584

ABSTRACT

Protein components of the invertebrate occluding junction-known as the septate junction (SJ)-are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell (BC) migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and the most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 11. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 like SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the BC cluster results in BC migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggest that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Tight Junctions/genetics , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Intercellular Junctions/genetics , Intercellular Junctions/metabolism , Oogenesis/genetics , Cell Movement/genetics
13.
J Dev Biol ; 9(1)2021 Mar 21.
Article in English | MEDLINE | ID: mdl-33801162

ABSTRACT

The septate junction (SJ) provides an occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the occluding junction, suggesting that SJ proteins possess non-occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the junction versus resident or accessory proteins, and the steps involved in the biogenesis of the junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the occluding junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts.

14.
Biochimie ; 185: 43-52, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33609630

ABSTRACT

The composition and metabolic activity of the microbiome affect many aspects of health, and there is current interest in dietary constituents that may affect this system. The purpose of this study was to evaluate the effects of a mix of probiotics, a mix of prebiotics and a bioactive protein fraction on the microbiome, when fed to mice alone and in combination at physiologically relevant doses. Mice were fed the total western diet (TWD) supplemented with prebiotics, probiotics, and bioactive proteins individually and in combination for four weeks. Subsequently, effects on the composition of the gut microbiome, gut short-chain fatty acids (SCFAs) concentration, and gut inflammation were measured. Ruminococcus gnavus was increased in mice gut microbiome after feeding prebiotics. Bifidobacterium longum was increased after feeding probiotics. The treatments significantly affected beta-diversity with minor treatment effects on cecal or fecal SCFAs levels, and the treatments did not affect gut inflammation as measured by fecal calprotectin.


Subject(s)
Dietary Supplements , Feces/microbiology , Gastrointestinal Microbiome/drug effects , Leukocyte L1 Antigen Complex/metabolism , Prebiotics , Probiotics/pharmacology , Animals , Mice
15.
Genetics ; 216(4): 1137-1152, 2020 12.
Article in English | MEDLINE | ID: mdl-33115752

ABSTRACT

Imaginal disc morphogenesis during metamorphosis in Drosophila melanogaster provides an excellent model to uncover molecular mechanisms by which hormonal signals effect physical changes during development. The broad (br) Z2 isoform encodes a transcription factor required for disc morphogenesis in response to 20-hydroxyecdysone, yet how it accomplishes this remains largely unknown. Here, we use functional studies of amorphic br5 mutants and a transcriptional target approach to identify processes driven by br and its regulatory targets in leg imaginal discs. br5 mutants fail to properly remodel their basal extracellular matrix (ECM) between 4 and 7 hr after puparium formation. Additionally, br5 mutant discs do not undergo the cell shape changes necessary for leg elongation and fail to elongate normally when exposed to the protease trypsin. RNA-sequencing of wild-type and br5 mutant leg discs identified 717 genes differentially regulated by br, including a large number of genes involved in glycolysis, and genes that encode proteins that interact with the ECM. RNA interference-based functional studies reveal that several of these genes are required for adult leg formation, particularly those involved in remodeling the ECM. Additionally, brZ2 expression is abruptly shut down at the onset of metamorphosis, and expressing it beyond this time results in failure of leg development during the late prepupal and pupal stages. Taken together, our results suggest that brZ2 is required to drive ECM remodeling, change cell shape, and maintain metabolic activity through the midprepupal stage, but must be switched off to allow expression of pupation genes.


Subject(s)
Drosophila Proteins/metabolism , Gene Expression Regulation, Developmental , Imaginal Discs/growth & development , Insect Hormones/metabolism , Morphogenesis , Transcription Factors/metabolism , Animals , Drosophila Proteins/genetics , Drosophila melanogaster , Extracellular Matrix/metabolism , Glycolysis , Imaginal Discs/metabolism , Signal Transduction , Transcription Factors/genetics
16.
Nutr Res ; 78: 1-10, 2020 06.
Article in English | MEDLINE | ID: mdl-32247914

ABSTRACT

Animal models of chronic disease are continuously being refined and have evolved with the goal of increasing the translation of results to human populations. Examples of this progress include transgenic models and germ-free animals conventionalized with human microbiota. The gut microbiome is involved in the etiology of several chronic diseases. Therefore, consideration of the experimental conditions that may affect the gut microbiome in preclinical disease is very important. Of note, diet plays a large role in shaping the gut microbiome and can be a source of variation between animal models and human populations. Traditionally, nutrition researchers have focused on manipulating the macronutrient profile of experimental diets to model diseases such as metabolic syndrome. However, other dietary components found in human foods, but not in animal diets, can have sizable effects on the composition and metabolic capacity of the gut microbiome and, as a consequence, manifestation of the chronic disease being modeled. The purpose of this review is to describe how food matrix food components, including diverse fiber sources, oxidation products from cooking, and dietary fat emulsifiers, shape the composition of the gut microbiome and influence gut health.


Subject(s)
Chronic Disease , Diet , Disease Models, Animal , Food , Gastrointestinal Microbiome , Animals , Dietary Fiber , Food Handling , Humans , Mice
17.
Nutrients ; 12(2)2020 Feb 20.
Article in English | MEDLINE | ID: mdl-32093192

ABSTRACT

Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis. In multiple experiments using the azoxymethane + dextran sodium sulfate or ApcMin/+ mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa.


Subject(s)
Colitis/complications , Colorectal Neoplasms/etiology , Diet, Western/adverse effects , Adaptive Immunity , Animals , Azoxymethane , Carcinogenesis/immunology , Cell Transformation, Neoplastic/immunology , Colitis/chemically induced , Colitis/immunology , Colon/immunology , Colon/metabolism , Colorectal Neoplasms/immunology , Dextran Sulfate , Disease Models, Animal , Immunity, Innate , Inflammation , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Mice , Mice, Inbred C57BL , RNA, Messenger/immunology , RNA, Messenger/metabolism
18.
Adv Nutr ; 9(3): 263-271, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29635305

ABSTRACT

Rodent models have been invaluable for biomedical research. Preclinical investigations with rodents allow researchers to investigate diseases by using study designs that are not suitable for human subjects. The primary criticism of preclinical animal models is that results are not always translatable to humans. Some of this lack of translation is due to inherent differences between species. However, rodent models have been refined over time, and translatability to humans has improved. Transgenic animals have greatly aided our understanding of interactions between genes and disease and have narrowed the translation gap between humans and model animals. Despite the technological innovations of animal models through advances in genetics, relatively little attention has been given to animal diets. Namely, developing diets that replicate what humans eat will help make animal models more relevant to human populations. This review focuses on commonly used rodent diets that are used to emulate the Western dietary pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver disease, maternal nutrition, and colorectal cancer.


Subject(s)
Animal Feed , Diet, Western , Disease Models, Animal , Rodentia , Animals , Animals, Genetically Modified , Colorectal Neoplasms , Diabetes Mellitus, Type 2 , Female , Humans , Non-alcoholic Fatty Liver Disease , Obesity , Pregnancy
19.
Adv Physiol Educ ; 42(1): 104-110, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29357270

ABSTRACT

The Kansas-IDeA Network of Biomedical Research Excellence (K-INBRE) is an infrastructure-building program funded by the National Institute of General Medical Sciences. Undergraduate education, through undergraduate research, is a key component of the program. The K-INBRE network includes 10 higher education institutions in Kansas and northern Oklahoma, with over 1,000 student participants in 16 yr. Since 2003, the K-INBRE has held an annual state-wide research symposium that includes national and regional speakers and provides a forum for undergraduates to give platform and poster presentations. The symposium is well attended by K-INBRE participants and has grown to a size of over 300 participants per year from all 10 K-INBRE schools. Two surveys were distributed to students and mentors to assess the impact of the symposium on student learning. Surveys (153) were distributed to students who participated in K-INBRE from 2013 through 2015 with a 51% response rate. Mentors were surveyed with a response of 111 surveys out of 161. Survey results indicate that students and mentors alike find the symposium to be beneficial and enriching of the student experience. Almost 80% of student respondents indicated that their participation in the symposium fostered appreciation of research. In short, the K-INBRE symposium provides a unique opportunity for students to gain experience in collecting, preparing, and communicating research in a professional environment. The collaborative experience of the annual K-INBRE symposium, the impact it has on student learning, and how it has influenced the research culture at our 10 institutions will be described.


Subject(s)
Biomedical Research/education , Congresses as Topic , Education, Medical, Undergraduate/methods , Interdisciplinary Placement/methods , Universities , Adult , Aged , Biomedical Research/trends , Congresses as Topic/trends , Education, Medical, Undergraduate/trends , Female , Humans , Interdisciplinary Placement/trends , Kansas , Male , Middle Aged , Surveys and Questionnaires , Universities/trends , Young Adult
20.
Mol Nutr Food Res ; 61(4)2017 04.
Article in English | MEDLINE | ID: mdl-27921383

ABSTRACT

SCOPE: In pre-clinical studies investigating bioactive components, the efficacy of the bioactive is likely influenced by the basal diet provided to rodents. In this study, we hypothesized that a model bioactive, green tea extract (GTE), would have different effects on colon carcinogenesis, body composition, and lipid metabolism in mice fed a basal diet formulated to promote animal health and growth (AIN93G) as compared to a Western diet that emulates typical American intakes of micro- and macronutrients, the total Western diet (TWD). METHODS AND RESULTS: Mice were fed either AIN93G or TWD, with or without GTE added to drinking water for 18 weeks. Aberrant crypt foci (ACF) in azoxymethane-initiated mice was nearly three times greater in mice fed TWD compared to AIN93G. Consumption of GTE suppressed ACF development only in mice fed the TWD. Similarly, supplementation with GTE suppressed weight gain and fasted glucose only in mice fed TWD, while GTE suppressed fat mass in mice fed either diet. Irrespective of diet, GTE supplementation increased cecum weight and decreased cecal SCFA concentration. CONCLUSION: Collectively, these observations indicate that the TWD influences the bioactivity of GTE in rodent models of obesity, metabolism, and carcinogenesis.


Subject(s)
Diet, Western , Tea/chemistry , Animals , Azoxymethane , Blood Glucose/analysis , Body Weight , Dietary Fats/metabolism , Glucose , Lipid Metabolism , Liver/metabolism , Male , Mice , Models, Animal , Obesity/metabolism
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