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New research successfully used human organ-on-chip technology to investigate the trigger of inflammation and the start of disease in the human gut. They also analyzed the consequences of probiotics treatment.
The gastrointestinal tract is a vital organ system of the body. The human intestine, an important part of the gut, performs some important functions such as digestion, absorption, secretion, and motility. The intestine also regulates the gut microenvironment by metabolizing drugs and communicating with other organs. Most of the bacteria in the gut microbiome are probiotics that are beneficial for optimal gut health. A healthy gut influences our immune system and metabolism and is important for long-term vitality.
The intestinal epithelium serves as a protective barrier
The intestinal epithelium is a single layer of cells that serves as a selectively permeable barrier between the digestive environment and the body. It permits the transport of nutrients, water, and waste products. It also acts as an important barrier between the gut microbiome, the underlying immune system, and the rest of the body.
Past research has shown an association between a compromised intestinal barrier and the development of inflammatory diseases such as inflammatory bowel disease (IBD), sometimes referred to as a “leaky gut”.
Challenges in the study of gut inflammation
Many studies have identified the trigger for gut inflammation. However, due to the complex parameters involved in gut inflammation, it has been challenging to develop a model that can overcome these complexities.
For instance, in animal or in vitro culture models, it has not been possible to disassociate the various contributing factors of inflammation. These methods also cannot support the growth of different cell cultures of microbiome because the microbiome bacteria grow rapidly and contaminate human cell culture. Therefore, there is a need for a technology that can enable researchers to understand the complex inflammatory process and the effect of each contributing factor one at a time.
New technology overcomes the challenges of studying gut inflammation
Organs-on-chips are microchips lined by living human cells. They have been used to study organ functions in a controlled environment. Recently, the researchers at the University of Texas in the United States developed a microfluidic organ-on-chip model of the human intestine.
These chips are cell culture devices that contain continuously perfused chambers inhabited by living intestinal cells that simulate tissue and organ physiology. The fluidic control of these organ-on chip models allows delivery of nutrients, drugs, toxins, or even probiotics to the intestinal epithelium grown on the microfluidic channels. Since this model enables addition, removal, and exchange of inflammatory factors, the researchers used it to emulate the intercellular activity during inflammation.
Study identifies the trigger of human intestinal inflammation
A new study published in the Proceedings of the National Academy of Sciences investigated the mechanism of inflammation and identified the trigger of intestinal inflammation by using inflammation-on-a-chip technology. The researchers induced intestinal inflammation using dextran sodium sulfate, a polymer known to cause colitis.
Dextran sodium sulfate treatment resulted in impaired function of the epithelial barrier, changes in the shape and size of intestinal villi, and decreased mucus production. All these changes reverted to normal once the DS treatment was withdrawn. The researchers studied these changes to analyze how gut microbiome, inflammatory cells, and epithelial deformations contribute to intestinal inflammation.
Impaired intestinal barrier leads to the onset of inflammation
The researchers observed that direct contact of the dysfunctional intestinal epithelium and immune cells led to increased oxidative stress, which is an imbalance between free radicals and antioxidants, thus eliciting the production of inflammatory cytokines.
On the other hand, an intact intestinal epithelial barrier suppressed oxidative stress and production of an inflammatory cytokine. These results show that impaired integrity of the intestinal barrier is the trigger to initiate the inflammatory cascade.
Probiotic treatment failed to improve epithelial barrier dysfunction
Probiotics are considered to be a beneficial therapy for gut inflammation. But in this study, the researchers observed that probiotics failed to improve the intestinal epithelial function if given after barrier dysfunction was already induced.
Interestingly, when the epithelial barrier was intact, probiotics effectively reduced the oxidative stress and inflammation. Therefore, it is important to note that the epithelial barrier function is an important determinant of the effectiveness of probiotics in improving gut health.
Probiotics are only beneficial when the gut barrier is healthy
This first-of-its-kind study highlights that a dysfunctional intestinal barrier is the most critical trigger for the onset of intestinal inflammation. The researchers suggest that the integrity of the intestinal barrier is necessary and sufficient to suppress inflammation. Leaky gut, on the other hand, is more susceptible to chronic inflammation.
Furthermore, probiotics are beneficial only when the gut barrier is healthy. In fact, probiotic administration may have detrimental effects when the barrier function is impaired.
In conclusion, the maintenance of an intact intestinal barrier is the most important factor in determining the entire gut inflammatory cascade. It is also essential for an effective use of probiotics.
With this knowledge of the root cause of gut inflammation, the researchers are optimistic about the possibility of developing effective and target-specific anti-inflammatory treatments.
Written by Preeti Paul, MS Biochemistry
Reference: Shin W, Kim H. Intestinal barrier dysfunction orchestrates the onset of inflammatory host–microbiome cross-talk in a human gut inflammation-on-a-chip. 2018.