![]() Suppression of peristalsis also has been strongly associated with intestinal pathology, inflammation ( 4, 5), and small intestinal bacterial overgrowth ( 5, 6) in patients with Crohn’s disease ( 7) and ileus ( 8). Various types of inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, involve chronic inflammation of human intestine with mucosal injury and villus destruction ( 1), which is believed to be caused by complex interactions between gut microbiome (including commensal and pathogenic microbes) ( 2), intestinal mucosa, and immune components ( 3). Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. ![]() This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. ![]()
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