Abstract
The intestinal microbiome affects a number of biological functions of the organism. Although the animal model is a powerful tool to study the relationship between the host and microbe, a physiologically relevant in vitro human intestinal system has still unmet needs. Thus, the establishment of an in vitro living cell-based system of the intestine that can mimic the mechanical, structural, absorptive, transport and pathophysiological properties of the human intestinal environment along with its commensal bacterial strains can promote pharmaceutical development and potentially replace animal testing. In this paper, we present a microfluidic-based gut model which allows co-culture of human and microbial cells to mimic the gastrointestinal structure. The gut microenvironment is recreated by flowing fluid at a low rate (21 μL/h) over the microchannels. Under these conditions, we demonstrated the capability of gut-on-a-chip to recapitulate in vivo relevance epithelial cell differentiation including highly polarized epithelium, mucus secretion, and tight membrane integrity. Additionally, we observed that the co-culture of damaged epithelial layer with the probiotics resulted in a substantial responded recovery of barrier function without bacterial overgrowth in a gut-on-a-chip. Therefore, this gut-on-a-chip could promote explorations interaction with host between microbe and provide the insights into questions of fundamental research linking the intestinal microbiome to human health and disease.
Highlights
The intestine is a primary organ for digestion, absorption, and metabolism of the nutrients and drugs, establishing a protective barrier between the pathogen and other harmful microorganisms in a human body [1,2,3]
To investigate the interactions between microbiomes and human Human intestinal epithelial cells (Caco-2) cells in a human intestinal microenvironment, we developed a microfluidic-based gut-on-a-chip embedding with microelectrode arrays (Fig. 1A)
The gut-on-a-chip consisted of three parallel microchannels (500 μm wide, 10 mm long, 150 μm high) separated by the hexagonal-shaped micropillars: two stromal cell culture channels which could mimic the epithelium or endothelium layer and one central channel filled with collagen type I gel (Fig. 1A, right)
Summary
The intestine is a primary organ for digestion, absorption, and metabolism of the nutrients and drugs, establishing a protective barrier between the pathogen and other harmful microorganisms in a human body [1,2,3]. The gut microbiome significantly contributes toward protection of the hosts against pathogenic incursions by enhancing the host defense mechanism [6]. For this reason, an imbalance between the composition and function of the intestinal microbes is associated with a number of diseases, such. To study the interaction between gut microbiomes and host cells, there have been great efforts to develop experimental in vitro and in vivo models of the intestinal system that can be used to analyze intestinal physiology both in the present and absence of living gut microbiomes [10].
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