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Principal Investigator: Luisa Cervantes Barragan
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $5,596
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Summary
Crohn’s disease and Ulcerative colitis collectively referred as inflammatory bowel disease (IBD)
are diseases in which an aberrant intestinal immune response leads to chronic inflammation. IBD
affects an estimated 1.5 million Americans, 2.2 million people in Europe and hundreds of
thousands in the rest of the world. The pathogenesis of IBD, while not completely elucidated, is
thought to be multifactorial and caused by the interplay of genetics, the microbiome and the
environment. One of the major environmental factors associated with increasing the risk for IBD
is the diet that an individual consumes. Therefore, the ability to harness nutrition to treat disease
is a unique opportunity for profound intervention in IBD progression. The major challenge for
implementing dietary therapy for IBD is the lack of understanding of detailed mechanistic
pathways to explain the impact of dietary interventions on IBD severity or progression.
Epidemiological studies of IBD have shown dietary fiber as the most consistent macronutrient
associated with changing risk of IBD. Fiber affects several aspects of the digestive process.
Notably, it is also a main energy source for several bacterial species of the microbiome, and
differences in fiber consumption strongly affect the microbiome composition and metabolic
behavior. However, very few studies have systematically addressed the role of fiber consumption
in fluctuations of the microbiome that lead to specific changes in the intestinal immune response.
The overall goal of this project is to discover relevant dietary fiber-microbe-immune cell
interactions that prevent, induce or alter the course of gut inflammation. We will analyze the
changes in microbiota composition and intestinal cell populations caused by the lack of
fermentable fiber intake using a model in which mice are fed a complex diet that contains
fermentable and non-fermentable fiber or semi-purified ingredients diet lacking fermentable fiber.
Moreover, we will select purified fibers representing different fiber types and supplement them in
the non-fermentable diet to identify those whose consumption modulate intestinal responses in a
healthy state and during inflammation. Finally, to assess the impact of consuming a diet lacking
fermentable fiber on the immune system in the context of human microbiota, we will colonize germ
free mice with healthy human donor fecal samples and feed them either a mixed fiber, a non-
fermentable fiber or a non-fermentable fiber diet supplemented with specific fibers to identify
specific fiber supplementations that result in the modulation of immune responses by human
microbiota, as well as the bacterial members mediating this interaction.
Terms: <Address><Affect><American><Bacteria><Behavior><Body Weight decreased><C rodentium><C. rodentium><C57BL/6 Mouse><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CTLA-8><CTLA-8 Gene><CTLA8><CTLA8 Gene><Carbon><Cell Body><Cell Communication><Cell Function><Cell Interaction><Cell Physiology><Cell Process><Cell-to-Cell Interaction><Cells><Cellular Function><Cellular Physiology><Cellular Process><Chronic><Citrobacter freundii Biotype 4280><Citrobacter rodentium><Colitis><Colon><Complex><Consumption><Crohn disease><Crohn's><Crohn's disease><Crohn's disorder><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Antigen 8 Gene><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8 Gene><Development><Diet><Diet therapy><Dietary Fiber><Dietary Intervention><Disease><Disease Progression><Disorder><Energy-Generating Resources><Environment><Environmental Factor><Environmental Risk Factor><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Europe><Fiber><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Food><Functional Metagenomics><GI microbiota><Gastrointestinal microbiota><Genetic><Germ-Free><Goals><Granulomatous Enteritis><Gut Mucosa><Health><Histologic><Histologically><Human><IL-17><IL-17 Gene><IL-17A><IL-17A Gene><IL17><IL17 Protein><IL17 gene><IL17A><IL17A Gene><Ileitis><Immune><Immune infiltrates><Immune response><Immune system><Immunes><Immunological response><Immunomodulation><Individual><Inflammation><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Intake><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8) Gene><Interleukin 17 Precursor><Interleukin 17 Precursor Gene><Interleukin-17><Intervention><Intervention Strategies><Intestinal><Intestinal Mucosa><Intestines><LCN2><LCN2 gene><Lamina Propria><Large Intestine><Lipocalin 2><Macronutrients><Macronutrients Nutrition><Measures><Mediating><Metabolic><Metabolic Pathway><Metagenomics><Mice><Mice Mammals><Microbe><Modeling><Modern Man><Mucosa><Mucosal Inflammation><Mucosal Tissue><Mucositis><Mucous Membrane><Murine><Mus><NGAL><Neutrophil Gelatinase-Associated Lipocalin><Nutrition Interventions><Nutritional Interventions><Oncogenic Lipocalin 24P3><Pathogenesis><Pathology><Pathway interactions><Persons><Population><Process><Regulation><Regulatory T-Lymphocyte><Research><Rest><Risk><Role><Series><Severities><Severity of illness><Short-Chain Fatty Acids><Small Intestines><Structure><Subcellular Process><Supplementation><T gondii><T-Cell Development><T-Cell Ontogeny><T-Cells><T-Lymphocyte><T-Lymphocyte Development><T. gondii><T4 Cells><T4 Lymphocytes><Toxoplasma gondii><Treg><Ulcerated Colitis><Ulcerative Colitis><Uterocalin><Volatile Fatty Acids><Weight Loss><Weight Reduction><body weight loss><bowel><bowel inflammation><cytokine><design><designing><developmental><diet intervention><dietary><dietary constituent><dietary therapy><diets><disease severity><eleocolitis><energy source><enteric microbial community><enteric microbiota><environmental risk><epidemiologic investigation><epidemiology study><experiment><experimental research><experimental study><experiments><fecal sample><feeding><flow cytophotometry><gain of function><gastrointestinal microbial flora><gut commensal><gut community><gut flora><gut inflammation><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiota><gut microbiotic><gut microflora><host response><human flora><human microbial communities><human microbiota><human microflora><human-associated microbial communities><human-associated microbiota><immune cell infiltrate><immune modulation><immune regulation><immune system response><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><inflamed bowel><inflamed gut><inflamed intestine><inflammatory disease of the intestine><inflammatory disorder of the intestine><interest><interventional strategy><intestinal autoinflammation><intestinal flora><intestinal inflammation><intestinal microbiota><intestinal microflora><intestinal tract microflora><intraepithelial><large bowel><member><microbial><microbial consortia><microbial flora><microbiome><microbiome community composition><microbiome composition><microbiome species composition><microbiome structure><microbiota><microbiota composition><microflora><mouse model><multispecies consortia><murine model><nutrition><nutritional approach><pathway><prevent><preventing><programs><regional enteritis><regulatory T-cells><response><small bowel><social role><stool sample><stool specimen><thymus derived lymphocyte><whole grain><wt-loss>