Nutrient-gene interactions and their role in complex diseases in dogs.
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Animal Nutritional Physiological Phenomena↗
Biomedical subjects
Kelly S Swanson
Publications and source records attributed to Kelly S Swanson.
Twists and turns in the development and maintenance of the mammalian small intestine epithelium.
Experimental studies during the last decade have revealed a number of signaling pathways that are critical for the development and maintenance of the intestinal epithelium and that demonstrate the molecular basis for a variety of diseases. The Notch-Delta, Wnt, Hedge Hog, TGF-beta, and other signaling pathways have been shown to form and steadily maintain the crypt-villus system, generating the proper quantities of highly-specialized cells, and ultimately defining the architectural shape of the system. Based on the characterized phenotypes and functional defects of mice resulting from various targeted knockouts, and overexpression and misexpressions of genes, a picture is emerging of the sequence of gene expression events from within the epithelium, and in the underlying mesenchyme that contribute to the regulation of cell differentiation and proliferation. This review focuses on the contributions of multiple signaling pathways to intestinal epithelial proliferation, differentiation, and structural organization, as well as the possible opportunities for cross-talk between pathways. The Notch pathway's potential ability to maintain and regulate the intestinal epithelial stem cell is discussed, in addition to its role as the primary mediator of lineage specification. Recent research that has shed light on the function of Wnt signaling and epithelial-mesenchymal cross-talk during embryonic and postnatal development is examined, along with data on the interplay of heparan sulfate proteoglycans in the signaling process.
Animals↗
Diet and age affect intestinal morphology and large bowel fermentative end-product concentrations in senior and young adult dogs.
The objective of this study was to determine the effects of age and diet on intestinal morphology and large bowel fermentative end-product concentrations in healthy dogs. Small intestinal villus width, height, and area, and small intestinal and colonic crypt depth were measured. Large bowel digesta samples were analyzed for ammonia, SCFAs, and branched-chain fatty acids (BCFAs). SCFAs are considered to be beneficial fermentative end-products in the intestine because they exert trophic effects on intestinal cells. Twelve senior (age = 11.1 y +/- 0.6 at baseline; 6 male, 6 female) and 12 young adult (age = 8 wk old at baseline; 6 male, 6 female) beagles were randomly assigned to 1 of 2 dietary treatments, an animal product-based diet (APB) and a plant product-based diet (PPB). Diets were fed for 12 mo. Jejunal (P = 0.03) and ileal (P = 0.02) villus height, and duodenal (P = 0.04) villus width were greater for dogs consuming the PPB diet. Young dogs had greater (P = 0.04) jejunal villus height, whereas senior dogs had greater (P < 0.001) colonic crypt depth. Ammonia concentrations decreased (P = 0.03) from proximal to distal colon and were higher in dogs consuming APB (P = 0.03). Age and treatment affected butyrate concentrations, with senior dogs (P = 0.04) and dogs consuming APB (P = 0.04) having higher concentrations. Both diet and age affected small and large intestinal morphology, and colonic fermentative end-product concentrations in dogs.
Animal Feed↗
Genomics and clinical medicine: rationale for creating and effectively evaluating animal models.
Because resolving human complex diseases is difficult, appropriate biomedical models must be developed and validated. In the past, researchers have studied diseases either by characterizing a human clinical disease and choosing the most appropriate animal model, or by characterizing a naturally occurring or induced mutant animal and identifying which human disease it best resembled. Although there has been a great deal of progress through the use of these methods, such models have intrinsic faults that limit their relevance to clinical medicine. The recent advent of techniques in molecular biology, genomics, transgenesis, and cloning furnishes investigators with the ability to study vertebrates (e.g., pigs, cows, chickens, dogs) with greater precision and utilize them as model organisms. Comparative and functional genomics and proteomics provide effective approaches for identifying the genetic and environmental factors responsible for complex diseases and in the development of prevention and treatment strategies and therapeutics. By identifying and studying homologous genes across species, researchers are able to accurately translate and apply experimental data from animal experiments to humans. This review supports the hypothesis that associated enabling technologies can be used to create, de novo, appropriate animal models that recapitulate the human clinical manifestation. Comparative and functional genomic and proteomic techniques can then be used to identify gene and protein functions and the interactions responsible for disease phenotypes, which aids in the development of prevention and treatment strategies.
Animals↗
Nutritional genomics: implications for companion animals.
This is an exciting time for biological scientists as the "omics" era continues to evolve and shape the way science is understood and conducted. As genome sequencing of the human comes to a close, other mammals are in line to be sequenced. Along with pigs and cows, dogs are now on the high priority list for sequencing, and cats may soon follow suit. Until sequence data are available, genetic maps may be used to reveal important physical characteristics of a genome. Genome mapping is important in identifying gene placement, but gives little information regarding function. Therefore, functional genomics, including the global analysis of RNA and protein expression, protein localization and protein-protein interactions will emerge as important areas of study. The major use of the dog and cat genome maps hitherto has been for the study of human and veterinary medicine. These powerful resources also can be applied to the field of nutritional genomics and proteomics, enhancing our understanding of metabolism and optimizing companion animal nutritional and health status. Genomics has begun to be applied to nutritional research, but issues specifically relevant to companion animals have not been elucidated thus far. The study of genomics and proteomics will be crucial in areas such as nutrient requirement determination, disease prevention and treatment, functional ingredient testing and others. Nutritional genomics and proteomics will definitely play a vital role in the future of pet foods.
Animal Nutritional Physiological Phenomena↗
Effects of supplemental fructooligosaccharides plus mannanoligosaccharides on immune function and ileal and fecal microbial populations in adult dogs.
The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) plus mannanoligosaccharides (MOS) influenced immune function and ileal and fecal microbial populations of adult dogs. Eight adult dogs surgically fitted with ileal cannulas were used in a crossover design. Dogs were fed 200 g of a dry, extruded, kibble diet twice daily. At each feeding, dogs were dosed with either 1 g sucrose (placebo) or 2 g FOS plus 1 g MOS orally via gelatin capsule. Fecal, ileal, and blood samples were collected at the end of each 14-d period to measure microbial populations and immune characteristics. Treatment least squares means were compared using the GLM procedure of SAS. Supplementation of FOS plus MOS increased fecal bifidobacteria and fecal and ileal lactobacilli concentrations. Dogs fed FOS plus MOS also tended to have lower blood neutrophils and greater blood lymphocytes vs placebo. Serum, fecal, and ileal immunoglobulin concentrations were unchanged by treatment. Supplementation of FOS plus MOS beneficially altered indices of gut health by improving ileal and fecal microbial ecology. Supplementation of FOS plus MOS also altered immune function by causing a shift in blood immune cells.
Animals↗
Fructooligosaccharides and Lactobacillus acidophilus modify bowel function and protein catabolites excreted by healthy humans.
The objective of this experiment was to determine whether supplementation with fructooligosaccharides (FOS) and (or) Lactobacillus acidophilus (LAC) affected bowel function and fermentative end-product concentrations in feces of healthy humans. Subjects (n = 68) were enrolled in a randomized, double-blind, placebo-controlled, parallel study design. After a 4-wk baseline period, subjects consumed one of the following treatments twice daily for 4 wk: 1) 3 g sucrose + 80 mg cornstarch; 2) 3 g FOS + 80 mg cornstarch; 3) 3 g sucrose + 1 x 10(9) colony-forming units (cfu) LAC; or 4) 3 g FOS + 1 x 10(9) cfu LAC. Subjects completed 7-d bowel function forms and 3-d dietary records before collection of fresh stool samples at wk 4, 6 and 8. Statistical analyses were performed on differences from baseline using the General Linear Models procedure of SAS. Fructooligosaccharides decreased fecal ammonia (P = 0.07) and isovalerate (P = 0.12) concentrations at wk 6. At wk 8, FOS tended (P = 0.11) to increase fecal putrescine concentrations. Lactobacillus decreased fecal organic matter percentage at wk 6 (P < 0.05) and 8 (P = 0.07). At wk 6 and 8, LAC increased (P < 0.05) fecal 2-methylindole, total indole, and total indole and phenol concentrations. At wk 8, LAC decreased fecal agmatine (P = 0.08) and phenylethylamine (P < 0.05) concentrations. In conclusion, FOS and LAC modified several metabolites associated with gut health, with FOS tending to be beneficial (decreased fecal protein catabolites) and LAC being negative (increased fecal protein catabolites).
Adult↗
Fructooligosaccharides and Lactobacillus acidophilus modify gut microbial populations, total tract nutrient digestibilities and fecal protein catabolite concentrations in healthy adult dogs.
The objective of this research was to determine whether fructooligosaccharides (FOS) and (or) Lactobacillus acidophilus (LAC) affected concentrations of gut microbial populations, fermentative end products and nutrient digestibilities in healthy adult dogs. Two experiments were performed using 40 adult dogs (20 dogs/experiment). Dogs in each experiment were randomly assigned to one of 4 treatments. Twice daily, treatments were given orally via gelatin capsules: 1) 2 g sucrose + 80 mg cellulose; 2) 2 g FOS + 80 mg cellulose; 3) 2 g sucrose + 1 x 10(9) colony forming units (cfu) LAC; or 4) 2 g FOS + 1 x 10(9) cfu LAC. Data were analyzed by the General Linear Models procedure of SAS. In Experiment 1, FOS resulted in lower (P = 0.08) Clostridium perfringens and greater fecal butyrate (P = 0.06) and lactate (P < 0.05) concentrations. In Experiment 2, FOS supplementation increased (P < 0.05) bifidobacteria, increased lactobacilli (P = 0.08), increased fecal lactate (P = 0.06) and butyrate (P < 0.05), and decreased (P < 0.05) fecal ammonia, isobutyrate, isovalerate and total branched-chain fatty acid concentrations. Dogs fed LAC had the highest fecal concentrations of hydrogen sulfide and methanethiol in Experiment 1 and dimethyl sulfide in Experiment 2, whereas dogs fed FOS had the lowest concentrations of these compounds. Overall, FOS appeared to enhance indices of gut health by positively altering gut microbial ecology and fecal protein catabolites, whereas LAC was more effective when fed in combination with FOS rather than fed alone.
Animals↗
Supplemental fructooligosaccharides and mannanoligosaccharides influence immune function, ileal and total tract nutrient digestibilities, microbial populations and concentrations of protein catabolites in the large bowel of dogs.
The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) and (or) mannanoligosaccharides (MOS) influenced indices of gut health of dogs. Adult female dogs (n = 4) surgically fitted with ileal cannulas were fed a dry, extruded, kibble diet twice daily. At each feeding, the following treatments were administered: 1) Control (no FOS or MOS); 2) 1 g FOS; 3) 1 g MOS; or 4) 1 g FOS + 1 g MOS. Fecal, ileal and blood samples were collected during the last 4 d of each 14-d period to measure protein catabolite concentrations, microbial populations, immune characteristics and nutrient digestibilities. Treatment means were compared using preplanned orthogonal contrasts. Dogs supplemented with MOS had lower (P = 0.05) fecal total aerobes and tended to have greater (P = 0.13) Lactobacillus populations. Ileal immunoglobulin (Ig) A concentrations were greater (P = 0.05) in dogs supplemented with FOS + MOS vs. control. Lymphocytes (% of total white blood cells) were greater (P < 0.05) in dogs supplemented with MOS. Serum IgA concentrations also tended (P = 0.13) to be greater in dogs supplemented with MOS. Dogs supplemented with FOS and FOS + MOS had lower (P < 0.05) fecal total indole and phenol concentrations. Dogs supplemented with MOS tended to have lower ileal DM (P = 0.149) and OM (P = 0.146) digestibilities vs. control. Results of this study suggest that dietary supplementation of FOS and MOS may have beneficial effects on colonic health and immune status of dogs.
Animals↗
Effects of supplemental fructooligosaccharides and mannanoligosaccharides on colonic microbial populations, immune function and fecal odor components in the canine.
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Animals↗