Human intestinal in vitro organ culture as a model for investigation of bacteria-host interactions

Human tissue samples are irreplaceable for studying genuine human host responses. Researchers have employed various in vitro and in vivo experimental models to study human intestinal infection. The currently available knowledge concerning enteric pathogens mainly derives from animal and in vitro cell culture studies with extrapolation to human situations. However, the high cost and paucity of suitable animal models of human diseases have diminished their widespread use. Thus, human intestinal in vitro organ culture (IVOC) has been developed and evolved from nonpolarized IVOC to polarized IVOC (pIVOC), providing an apical exposure to simulate an in vivo infection route. IVOC in the Ussing chamber to create a microaerobic environment and other variants of IVOC such as in vitro 3D organoid culture using stem cells were also developed. Despite a history of more than one century, the rapid progress of IVOC occurred in the past two decades, mainly for studying Escherichia coli. Human intestinal IVOC has been extensively applied to studies of various enteric infections ranging from chronic Helicobacter pylori infection to acute bacterial infections including diarrheagenic E. coli, Salmonella, Campylobacter jejuni, and Shigella, as well as bacterial toxin-related enteropathy. Some disclosed mechanisms and pathophysiology of human gastrointestinal infections by these bacteria were also discussed in this review. Altogether, human intestinal IVOC represents a valuable addition to traditional model systems to investigate early interactions between pathogenic bacteria and the human gut.