Microbes meet organoids

The impact of the variety of gut-dwelling bacteria, viruses, fungi and other parasites – our gut microbiota – in numerous diseases is one of the most actively investigated areas in medical research. However, these interactions are highly complex and findings from mouse models cannot always be properly translated to humans. Consequently, researchers are developing sophisticated models which recapitulate key features of the human intestinal tract in a petri dish.

Organoids and organs-on-a-chip

Some of these models, such as cell lines or -cultures grown from patient tumors, have been in use for many decades. However, recent breakthroughs in organoid- and organ-on-chips technology have ushered in a new era of in vitro modelling of host-microbe interactions in the human gut. These technologies allow researchers to grow cell structures that mimic organ function. Organoids and organs-on-a-chip can be cultured from a wide range of organs and from both healthy or sick tissue.

These new co-culture models have vastly improved our ability to study the role of individual microbes or even microbe-communities in diseases such as colorectal cancer or inflammatory bowel disease. Additionally, co-cultures allowed studying coronavirus infection of the intestine and the complex life cycle of the gut parasite Cryptosporidium parvum.

Promising developments

In their review paper, PhD students Jens Puschhof and Cayetano Pleguezuelos-Manzano from the group of Hans Clevers discuss the numerous processes by which microbes can interact with the epithelial layer – the layer of cells that lines the human intestinal tract. They provide detailed comparisons and case studies to highlight the suitability of each model system to model the individual interaction processes. Having used and developed some of these co-culture models during their shared work over the last years, they reflect on the main advances of this period, current trends and finish with an outlook of some of the most promising developments which can be anticipated for the next years.

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