Models of the Gut for Analyzing the Impact of Food and Drugs

Abstract

The human intestine is the primary organ responsible for the uptake of nutrients and water, and this is facilitated by its complex structure that features a large surface area. With an average total length of around seven meters, including both small and large intestine, it connects the stomach to the rectum while enabling absorption in a specialized manner. At a cellular level, the gut epithelium is critical in selective transport to the bloodstream. The finger-like projections of the intestinal epithelium Models of the human gastrointestinal tract (GIT) can be powerful tools for examining the biological interactions of food products and pharmaceuticals. This can be done under normal healthy conditions or using models of disease-many of which have no curative therapy. This report outlines the field of gastrointestinal modeling, with a particular focus on the intestine. Traditional in vivo animal models are compared to a range of in vitro models. In vitro systems are elaborated over time, recently culminating with microfluidic intestines-on-chips (IsOC) and 3D bioengineered models. Macroscale models are also reviewed for their important contribution in the microbiota studies. Lastly, it is discussed how in silico approaches may have utility in predicting and interpreting experimental data. The various advantages and limitations of the different systems are contrasted. It is posited that only through complementary use of these models will salient research questions be able to be addressed.

An Intestine-on-a-Chip Model of Plug-and-Play Modularity to Study Inflammatory Processes

“…11 Although these models are relevant and pertinent to the field of intestinal inflammation modeling, they lack the robustness or relationship to industryadopted cellular standards and are generally not suitable for screening large libraries of compounds. 15 Previously, we introduced an intestinal model comprising perfused tubules composed of the intestinal cell line Caco-2 in a microfluidic platform, the OrganoPlate. 16 The gut tubules showed accelerated cellular polarization, fundamental receptor expression, and tight junction formation in a robust and reproducible manner.…”

“… 11 Although these models are relevant and pertinent to the field of intestinal inflammation modeling, they lack the robustness or relationship to industry-adopted cellular standards and are generally not suitable for screening large libraries of compounds. 15 …”

Orally ingestible medical devices for gut engineering

“…Furthermore, Kim et al implemented key characteristics of intestinal inflammation diseases, including destruction of intestinal villi and associated compromise of the permeability barrier [43]. These damages are believed to origin from interplays between the intestinal epithelium, gut microbes and immune cells and changes in luminal flow due to altered peristalsis [44,45] The developed in vitro human gut-on-a-chip microfluidic device could potentially be further developed to work in a patient specific manner to advance personalized medicine in the futurepassive OIMs can play a key-role in developing personalized medicine and can be tested in these gut-on-a-chip systems as well [46,47,48] For instance, Workman et al demonstrated induced pluripotent stem cells (iPSCs) derived intestinal organoids to express intestine markers (post-14 days differentiation), and their association with IBD was studied upon exposure to the IFN-γ cytokine [49]. A two-channel PDMS mold was created where cell-monolayer was maintained in the top-channel (1000 μm high), followed by a thin porous membrane (7 μm~pore size), and growth media being circulated in the bottom-channel (200 μm high).…”

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

“…Animal models, including mice, fish, and insects, have been extensively used to analyze host-microbiome interactions and their contributions to pathophysiology in infectious diseases regarding diet. Mice are the model of choice for most studies in this emerging field, allowing for manipulations in the gut microbiota and host to be studied in a controlled experimental setup [32]. Manipulations include host genetic background manipulation (gene knockouts); gut microbiota composition manipulation (controlled inoculation in germ-free or gnotobiotic mice, i.e., germ-free mice administered with human microbes); and ecosystem interventions, including dietary interventions, antibiotic treatment, and fecal transplantations.…”