Innovations in Colon Epithelial Models: Understanding Interactions with Low-Oxygen Microbiota

Abstract

Our body requires a well-functioning digestive system to break down food, absorb nutrients, and maintain a healthy balance. The intestines are essential for these processes and form a complex system in our body. In the gut, there are diverse types of bacteria that help keep the body healthy, such as by protecting against pathogens and supporting metabolism. This group of bacteria, known as the microbiome, varies from person to person and is influenced by lifestyle, environment, and diet. When this group of bacteria becomes imbalanced, it can lead to health issues such as chronic inflammation or colon cancer. Microbiota are in direct contact with the intestinal epithelium, which acts as a barrier against harmful substances from outside the body. To better understand these interactions, models are being developed to replicate the cooperation between the epithelium and microbiota. The gut forms a complex system, making it difficult to replicate. The epithelium, for example, consists of distinct types of cells that renew themselves and produce mucus, which is important for digestion and protection. Cell lines are often used in research, but they lack many properties of the intestinal epithelium. Animal models, such as mice, are also used, but their use has many drawbacks. New techniques are being developed, such as organoids, which better replicate the structure and functions of the intestinal epithelium. However, growing these in combination with oxygen-sensitive bacteria remains challenging. To overcome this challenge, culture models have been developed that support both aerobic epithelial cells and anaerobic microbiota. These models aim to recapitulate key functions of the intestinal epithelium, such as barrier integrity and mucus production. They vary in the features they replicate, ranging from static to dynamic models, and support both direct and indirect cultures. Co-cultures with host and microbiota can last from short-term to more long-term studies. This review focuses on models designed specifically for low-oxygen microbiota cultures, providing a clear overview of current developments. The key features of these models are summarized in Table 1. The search for the ideal model continues, and this review highlights improvements that could enhance the development of culture models in the future.