Can a Miniature Gut-in-a-Chip Solve the Mystery of Microbial Health?

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Healthcare (Commonwealth Union) – Scientists from the National University of Singapore (NUS) have made a significant advancement in gut health research by creating a 3D microscopic model of the human intestines on a chip, called the Gut-Microbiome on a Chip (GMoC). This innovative cell culturing platform, which is half the size of a five-cent coin, offers a realistic and scalable in vitro microgut model. It enables researchers to efficiently study the interactions of gut microbes and their collective influence on gut health, which is crucial for the preventive healthcare and pharmaceutical industries.

“The GMoC system represents a significant advancement in our ability to investigate the effect of the gut microbial community on gut health and diseases,” explained Professor Lim Chwee Teck, who is Director of the NUS Institute for Health Innovation and Technology (iHealthtech). Prof Lim is from the Department of Biomedical Engineering at the College of Design and Engineering, NUS, as well. “By establishing a physiologically relevant gut model capable of culturing communities of gut microbes, we can gain deeper insights into the role and complex mechanisms of these micro-organisms in maintaining gut health and preventing disease.”

The results appeared in the journal Advanced Science on 27 February last year.

Researchers of the study pointed out that intestines are home to trillions of bacteria, fungi, and viruses that play a vital role in maintaining our health. Collectively known as the gut flora or gastrointestinal microbiome, these microorganisms can be either beneficial or harmful to our well-being.

Despite their importance, the precise ways in which these microbes contribute to gut health or trigger digestive disorders remain largely unknown. While scientists have observed differences in the gut microbiomes of healthy individuals and those with various diseases, the intricate interactions among these vast microbial populations make it challenging to pinpoint their exact roles in disease prevention or progression.

To address this, researchers at NUS have developed an advanced 3D ‘microgut’ platform that offers a more accurate representation of the gut microbiome compared to existing models. This innovative system replicates key structural and physiological aspects of the intestinal lining, simulates biological conditions such as food movement and oxygen levels, and supports the cultivation of diverse microbial communities, enabling real-time and detailed study of gut microbe interactions.

The GMoC system offers an accurate in vitro (outside the body) representation of the human gut, incorporating a 3D model of the gut epithelium that reflects crucial structural and functional features of the intestinal tract. This includes the intestinal villi (small, finger-like projections that aid nutrient absorption), the coexistence of intestinal cells and microbes, and dynamic conditions simulating food movement.

Reproducing the structure of intestinal villi is vital because the precise positioning of different microbial species within a 3D environment affects their organization and function, which, in turn, impacts the gut’s response to various stimuli.

Beyond its structural aspects, the team’s ‘microgut’ platform also exhibits key characteristics of a functional and physiologically accurate intestinal epithelium. It is capable of producing mucin, which acts as a defense against microbial intrusion and plays a role in forming the gut-bacteria interface.

Thus, the GMoC system offers a more comprehensive in vitro model by accurately replicating the architecture of human intestinal cells and providing a model that better reflects physiological conditions compared to existing static in vitro systems.

The research team stated their dedication to advancing the device, with the goal of increasing its complexity to more accurately mimic human intestines. This involves adding intricate mechanical signals, improving cellular complexity, and establishing oxygen gradients within the GMoC system.

From a biological perspective, the team seeks to utilize the device for further exploration of how diverse microbial communities assemble, interact, and behave in response to various stimuli such as nutrients and antibiotics. This will enhance our understanding of how these interactions influence gut health.

Regarding commercialization, the team aims to make the device more accessible by lowering production costs and streamlining the manufacturing process.

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