NUS scientists develop realistic ‘micro-gut’ model to study the relationship between gut microbes and human diseases

Understanding the complex interplay of gut microbes and health

Our intestines contain trillions of bacteria, fungi, and viruses which play a crucial role in our overall well-being. These communities of microorganisms – also known collectively as the gut flora or gastrointestinal microbiome – can either help or harm us.

However, the exact mechanisms by which these gut microbes prevent or cause gastrointestinal illnesses remain unclear. While researchers have identified individual differences in the gut microbiomes of healthy people and those with diseases, the complexity of the interactions amongst the trillions of microorganisms residing in our intestines makes it difficult to isolate the exact modes of action by which these microbes protect us or induce disease.

The innovative 3D ‘microgut’ platform developed by NUS researchers provides a more realistic presentation of the gut microbial community compared to existing models. It simulates biological conditions (like food movement and oxygen levels) as in the human gut, mimics key structural and physiological features of the gut lining, allows for diverse communities of microbes to be cultivated, and is designed for easy and real-time investigation.

Mimicking the human gut

The GMoC system provides a realistic in vitro (outside the body) model of the human gut, featuring a 3D version of the gut epithelium that mimics key architectural and functional aspects of the intestinal tract, such as the intestinal villi (tiny finger-like projections for absorption of nutrients), co-inhabitation of microbes and intestinal cells, and the dynamic conditions simulating movement of food.

Replicating the structure of the intestinal villi is important because the specific location of different microbial species within a 3D substrate influences how they organise and function, and it also has a distinctive impact on the gut’s response to various stimuli.

In addition to structural features, the team’s ‘microgut’ platform also demonstrated key attributes of a functioning and physiologically-relevant intestinal epithelium. The ‘microgut’ can also produce mucin, which serves as a line of defence against microbial invasion and contributes to the establishment of the gut-bacteria interface.

The GMoC system is therefore a more complete in vitro model because it replicates, architecturally, the cells lining the human intestine, and offers a more physiologically-relevant model compared to existing static in vitro systems.

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