Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

Abstract

The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of Inflammatory Bowel Disease (IBD), namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial crosstalk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications such as patient-derived organoid biobanks for microbial screening and omics technologies are discussed, highlighting their potential to gain better mechanistic insights into disease mechanisms and eventually allowing personalized medicine.

The arthritis connection to inflammatory bowel disease (IBD): why has it taken so long to understand it?

“…A significant need in this regard, and what poses an important limitation to our knowledge, is the challenge of obtaining direct access to relevant tissues such as the intestine and the enthesis structures. Use of newer in vitro systems like organ-on-a-chip and intestinal organoids derived from human subjects has the potential to allow mechanistic studies including microbe-host interactions [92][93][94][95] without having to use murine models.…”

Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection

“…Yet, a recent study, where human intestinal CD4+ T cells have been co-cultured with human intestinal organoids (Schreurs et al, 2021), may represent a promising set-up for future studies to investigate epithelial-immune cell interactions during SARS-CoV-2 induced inflammation in the gut. As reviewed recently by (Min et al, 2020; Poletti et al, 2020), such co-culture systems could be excellent to study host-microbe interactions in the gut, including the detailed experimental analysis of SARS-CoV-2 infection in the gut.…”

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

“…The intestinal organoids have closed 3D structures where the apical surface of the epithelium is located inside the organoids, thus limiting the epithelial interactions with luminal contents ( 43 ). Therefore, microinjection is required to induce contacts between the microorganisms and the apical surface of the intestinal epithelium while mimicking in vivo physiology.…”

“…This suggests the hypoxic environment of the organoids with a sealed lumen and a mucus layer ( 29 ). However, given that the lumen of organoids is not in a perfect hypoxic state, it is difficult to sustain a stable co-culture with obligate anaerobic bacteria for a long period ( 43 ). In addition, it is hard to perform high-throughput experiment with the manually performed microinjection method; however, the recently reported system would allow us to approach high-throughput experiments ( 44 , 50 ).…”