Project Summary/Abstract
The Gastrointestinal (GI) system engages the coordinated function of digestive organs, oxygenated blood supply, nutrient
processing and distribution, detoxification of noxious species, and sequestration of excess bioactive nutrients to maintain
homeostasis and respond to the body's nutrient bioavailability. Excess gastrointestinal-produced bioactive nutrients such
as glucose or fructose, precursors to many gastrointestinal-related diseases, pose a major burden and risk to the liver due
to increased hepatic metabolism physiologically designed to process and sequester excess bioactive nutrients within
designated tissues of the body. Excess glucose and fructose due to dysregulation and high sugar content diets are among
the many contributors to non-alcoholic fatty acid (NAFLD) pathogenesis with fructose having more potential impact on
the etiology of this disease than glucose since it is only metabolized in the liver. In addition, fructose metabolism to fatty
acid in the liver is far less regulated than its glucose counterpart. However, glucose being an isomer of fructose, will be
used as the model compound for the proposed approach of remediating and optimizing excesses of these two hexose
molecules (glucose and fructose) in the proximal small intestine. The objective of this research project is to determine the
optimal dynamics for excess glucose remediation via fibration in the proximal small intestine (SI) lumen. This will be
accomplished by Identifying and quantifying mechanisms of species transport and physicochemical transformation at the
proximal small intestine with a focus on glucose bioavailability optimization and excess regulation. Determine the optimal
rates of glucose fibration relative to other transport and metabolic reaction rates at the proximal small intestine. GI
systems use biophysical and biochemical mechanisms in coordinating species transport and transformation coupled with
interactions with the wall of the GI lumen. A systematic representation of these mechanisms will serve as a platform for
the development of a numerical model that can assist in glucose transport and transformation rate quantification in the
proximal SI. While also assessing the optimal rate of glucose condensation to dietary fiber (NDO) involving the
transglycosylase enzyme in the proximal SI. The processes guiding the optimal rate determination encompass both the
species transport in and out of the proximal SI and the series of species transformations in the same. A compartmental
metabolic rate model for the proximal SI and other supporting organs serving as peripheral compartments will be
developed to model glucose formation, consumption through transglycosylation, absorption, and regulation rates with the
focus of optimizing its bioavailability and regulating its excess through transglycosylation (NDO formation). The
numerical model for the quantification and analysis of the proposed metabolism mechanisms will be developed and solved
in MATLAB (and COMSOL Multiphysics as an alternative). This effort will create a systematic gastrointestinal tract
virtual laboratory platform where detailed species transport and transformation mechanisms can be readily assessed and
quantified. This modeling approach can leverage our understanding of many gastrointestinal pathophysiological
conditions connected to excess glucose in the body and provide a systematic approach to developing diagnostic
procedures and therapeutic prescriptions per disease of interest.
