Role of dietary fiber-microbiota Interactions in the development and function of small intestinal T cells

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.

Grant Number: 5R01DK129950-05
NIH Institute/Center: NIH
Principal Investigator: Luisa Cervantes Barragan