Enteropathogenic Infections: Organoids Go Bacterial

Abstract

Enteric infections represent a major health care challenge which is particularly prevalent in countries with restricted access to clean water and sanitation and lacking personal hygiene precautions, altogether facilitating fecal-oral transmission of a heterogeneous spectrum of enteropathogenic microorganisms. Among these, bacterial species are responsible for a considerable proportion of illnesses, hospitalizations, and fatal cases, all of which have been continuously contributing to ignite researchers’ interest in further exploring their individual pathogenicity. Beyond the universally accepted animal models, intestinal organoids are increasingly valued for their ability to mimic key architectural and physiologic features of the native intestinal mucosa. As a consequence, they are regarded as the most versatile and naturalistic in vitro model of the gut, allowing monitoring of adherence, invasion, intracellular trafficking, and propagation as well as repurposing components of the host cell equipment. At the same time, infected intestinal organoids allow close characterization of the host epithelium’s immune response to enteropathogens. In this review, (i) we provide a profound update on intestinal organoid-based tissue engineering, (ii) we report the latest pathophysiological findings defining the infected intestinal organoids, and (iii) we discuss the advantages and limitations of this in vitro model.

From the Dish to the Real World: Modeling Interactions between the Gut and Microorganisms in Gut Organoids by Tailoring the Gut Milieu

“…In human intestinal organoid monolayers derived from the small intestine and colon, basolateral infection and intracellular replication of S. flexneri have been recapitulated ( 67 , 68 ). S. flexneri invasion in monolayers increased NF-κB-mediated inflammation signaling pathway and production of MUC2 ( 26 , 67 , 68 ). However, the apical invasion of S. flexneri can be increased by M cell induction or tight junction disruption in monolayers ( 67 , 68 ).…”

“…Subsequently, saccharolytic bacterial fermentation activity of normal intestinal microbiota generates beneficial SCFAs, lowering pH. Specifically, butyrate reduces epithelial oxygenation levels via β-oxidation of butyrate and thus prevents dysbiotic expansion of aerotolerant pathogens such as V. cholerae , S. enterica , and S. flexneri ( 26 , 132 , 133 ).…”

“…In this review, we will describe current efforts to use human organoids to model the interactions between commensal microorganisms or pathogens and the host. Since many reviews have already described extensively the various organoids in the context of pathogen interactions ( 26 - 29 ), we will focus on the interactions between enteric microorganisms and gut epithelium with specific emphasis on the gut milieu.…”

H-NOX proteins in the virulence of pathogenic bacteria

“…This is particularly true of V. cholerae, which does not infect other mammals. Human intestinal organoids have recently shown promise as a tractable, humane model for V. cholerae infection [85] as well as other enteric bacterial diseases [86]. Breakthrough systems such as these may reveal previously unrecognized roles for H-NOX in V. cholerae pathogenesis and potential strategies for managing this and other potentially deadly pathogens through NO signaling pathways.…”

Modellsysteme in der gastroenterologischen Forschung

“…Intestinale Organoide werden heutzutage zunehmend wegen ihrer Fähigkeit geschätzt, wichtige architektonische und physiologische Merkmale der nativen Darmschleimhaut nachahmen zu können. Aus diesem Grund sind intestinale Organoide das vielseitigste und natürlichste In-vitro-Modell des Darms, um sowohl biologische Prozesse, die für die Aufrechterhaltung der Gewebehomöostase wichtig sind, als auch die Immunantwort nach enteropathogenem Befall zu untersuchen [11].…”