Cover photograph (Copyright © 2015, American Society for Microbiology. All Rights Reserved.): (Center) Human intestinal organoids (HIOs) are three-dimensional spheroids derived from directed differentiation of pluripotent stem cells. HIOs have a complex epithelium, which recapitulates aspects of the human gastrointestinal tract. The epithelial cells of HIOs respond to cytokines, as treatment with tumor necrosis factor alpha and gamma interferon induces apoptosis (top left) while the calcium chelator EGTA does not (bottom right). Furthermore, HIOs can be colonized with anaerobic bacteria such as the gastrointestinal pathogen Clostridium difficile. Infection of HIOs with a toxigenic (bottom left) but not a nontoxigenic (bottom right) strain of C. difficile results in a disruption of the HIO epithelium. (See related article on page 138.)