Research Advances in Gut Inflammation and Probiotics
Human Organ-on-Chip Technology
Recent studies have successfully utilized human organ-on-chip technology to explore the triggers of inflammation and disease onset in the human gut. This innovative approach also allowed for the analysis of the effects of probiotic treatments.
The Role of the Gastrointestinal Tract
The gastrointestinal tract is a crucial organ system responsible for digestion, absorption, secretion, and motility. Within this system, the human intestine plays a vital role in regulating the gut microenvironment, metabolizing drugs, and facilitating communication with other organs. The gut microbiome, predominantly composed of beneficial probiotics, is essential for maintaining optimal gut health, influencing the immune system, metabolism, and overall vitality.
Protective Barrier of the Intestinal Epithelium
The intestinal epithelium consists of a single layer of cells that acts as a selectively permeable barrier, separating the digestive environment from the body. This barrier allows for nutrient, water, and waste transport while protecting against harmful substances. Previous research has linked a compromised intestinal barrier to inflammatory diseases such as inflammatory bowel disease (IBD), often referred to as a “leaky gut.”
Challenges in Studying Gut Inflammation
While numerous studies have identified triggers for gut inflammation, developing a model that accounts for the complexities involved has proven challenging. Traditional animal and in vitro culture models fail to disentangle the various contributing factors of inflammation. Additionally, these methods cannot sustain diverse microbiome cell cultures due to rapid bacterial growth that contaminates human cell cultures. Thus, innovative technology is needed to better understand the intricate inflammatory processes.
Innovative Technology for Gut Inflammation Research
Organs-on-chips are microchips lined with living human cells, designed to study organ functions under controlled conditions. Researchers at the University of Texas have recently developed a microfluidic organ-on-chip model of the human intestine. These cell culture devices contain continuously perfused chambers populated by living intestinal cells that mimic tissue and organ physiology. The fluidic control of these models allows for the introduction and removal of nutrients, drugs, toxins, or probiotics to the intestinal epithelium, enabling detailed analysis of intercellular activity during inflammation.
Identifying Triggers of Intestinal Inflammation
A new study published in the Proceedings of the National Academy of Sciences utilized inflammation-on-a-chip technology to investigate the mechanisms behind intestinal inflammation, specifically identifying triggers. The researchers induced inflammation using dextran sodium sulfate, a polymer known to cause colitis. This treatment led to impaired epithelial barrier function, alterations in intestinal villi structure, and reduced mucus production, all of which normalized after the treatment was withdrawn. The study examined how the gut microbiome, inflammatory cells, and epithelial deformations contribute to inflammation.
Impact of Impaired Intestinal Barrier
The researchers found that direct contact between dysfunctional intestinal epithelium and immune cells resulted in increased oxidative stress, leading to the production of inflammatory cytokines. Conversely, an intact intestinal barrier suppressed oxidative stress and inflammation. These findings indicate that the integrity of the intestinal barrier is crucial for preventing the inflammatory cascade.
Probiotics and Epithelial Barrier Dysfunction
While probiotics are generally considered beneficial for gut inflammation, this study revealed that they did not improve epithelial function when administered after barrier dysfunction was already present. However, when the epithelial barrier was intact, probiotics significantly reduced oxidative stress and inflammation. This underscores the importance of epithelial barrier integrity in determining the effectiveness of probiotics for gut health.
Conclusions on Gut Health and Probiotics
This groundbreaking study emphasizes that a dysfunctional intestinal barrier is a critical trigger for intestinal inflammation. The researchers concluded that maintaining the integrity of the intestinal barrier is essential for suppressing inflammation and effectively utilizing probiotics. Furthermore, probiotics may have adverse effects if the barrier function is compromised.
In summary, understanding the root causes of gut inflammation paves the way for developing targeted anti-inflammatory treatments. The research highlights the necessity of preserving an intact intestinal barrier to manage gut inflammation effectively.
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.