Ulcerative colitis is a chronic inflammatory bowel disease that primarily affects the colon and rectum. It is characterized by inflammation and superficial ulcers in the lining of the colon and rectum. Despite advances in treatment, including the use of steroids, non-steroidal anti-inflammatory drugs, and biologics, remission rates remain modest, highlighting the need for novel therapeutic approaches. One of the key aspects of ulcerative colitis is its negative impact on barrier function of the intestinal lining. In a healthy individual, this barrier is composed of a single layer of epithelial cells tightly joined together, along with a mucus layer and various immune cells. Restoring and maintaining the barrier function is a crucial aspect of managing ulcerative colitis. Treatments often focus on reducing inflammation, healing the epithelial lining, and modulating the immune response. Understanding the complex interplay between the intestinal barrier and immune response is key to developing more effective treatments for ulcerative colitis and improving the quality of life for those affected by this challenging condition. To this account, Aquamin®, a multi-mineral product sourced from the skeletal remains of red marine algae, rich in calcium, magnesium, and 72 trace minerals has shown previously its beneficial impact on barrier structure in colon organoids and in vivo trials. However, the ability of Aquamin® to maintain an effective barrier under inflammatory conditions remained unexplored. To address this, a new study published in the Journal Frontiers in Cell Developmental Biology by Professor James Varani, Mr. Shannon McClintock, Dr. Daniyal Nadeem, Ms. Isabelle Harber, Ms. Dania Zeidan, and Dr. Muhammad Aslam from the Department of Pathology at the University of Michigan Medical School undertook a detailed and methodical approach to assess the impact of Aquamin® on human colon organoids. According to Dr. Aslam, who is the corresponding author and leading researcher of the study, there is currently a need for safe therapeutic options available for individuals suffering from mild-to-moderate ulcerative colitis. These studies may hold the key to unlocking new and effective therapies for these patients.
First, the researchers established human colon organoids as the model system. Organoids are three-dimensional structures grown in vitro from stem cells and closely mimic the human colon both structurally and functionally. This model is particularly advantageous for studying intestinal pathophysiology and evaluating therapeutic interventions in a controlled environment. To simulate an environment akin to ulcerative colitis, the authors treated the organoids with a mix of lipopolysaccharide (LPS) and cytokines. LPS, a component of the outer membrane of certain bacteria, is known to trigger an immune response. The inclusion of pro-inflammatory cytokines further enhanced this model’s relevance to the inflammatory conditions seen in ulcerative colitis. The authors treated the organoids with Aquamin®. The treatment was administered both in the presence and absence of the LPS-cytokine mix, allowing the researchers to observe the effects of Aquamin® under both normal and inflammatory conditions. Afterward, the authors conducted a comprehensive proteomic analysis to identify changes in protein expression due to the Aquamin® treatment. Proteomic analysis revealed that Aquamin® altered the expression of a wide range of proteins within the organoids. Notably, it downregulated proteins associated with inflammation while upregulating those with anti-inflammatory, antioxidant, or anti-microbial properties and involved in improved barrier structure. This shift in protein expression suggests that Aquamin® could have a comprehensive impact on the cellular environment, countering inflammatory processes and promoting tissue health.
To visualize and analyze structural changes in the organoids, the researchers used confocal fluorescence microscopy, allowing for the assessment of changes in the expression and localization of key proteins involved in maintaining epithelial barrier integrity. Moreover, the researchers evaluated the structural integrity and functionality of the colon organoids by measuring tissue cohesion and transepithelial electrical resistance (TEER). These measurements provided quantitative data on barrier function of the organoids, indicating how well the cells were connected and the effectiveness of the epithelial barrier in preventing the passage of substances. The study also focused on how Aquamin® affected the organoids’ response to the pro-inflammatory stimulus. This aspect was crucial for understanding whether Aquamin® could not only maintain barrier integrity but also actively modulate the inflammatory response. It is noteworthy to mention that the authors demonstrated Aquamin®’s ability to enhance the structural integrity and function of the colon organoids. This was evident from the increased expression of desmoglein-2 and cadherin-17, proteins crucial for cell-cell adhesion, observed through confocal microscopy. Improved tissue cohesion and higher TEER values further corroborated this, indicating a stronger and more effective epithelial barrier.
In conclusion, the authors demonstrated that Aquamin®, with its unique multi-mineral composition, can combat inflammation in ulcerative colitis by improving barrier structure and function and by directly altering the expression of pro-inflammatory proteins and offers a promising therapeutic strategy that addresses a critical but often overlooked aspect of ulcerative colitis pathophysiology. Clinical trials in ulcerative colitis patients are essential to evaluate its efficacy and safety in a clinical setting. Furthermore, exploring the synergistic potential of Aquamin® with existing ulcerative colitis therapies could pave the way for more effective treatment regimens. At present, a pilot-phase trial on human subjects with ulcerative colitis, registered on clinicaltrials.gov under NCT03869905 is underway and will address some of these questions.
Varani J, McClintock SD, Nadeem DM, Harber I, Zeidan D, Aslam MN. A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids. Front Cell Dev Biol. 2023;11:1132905. doi: 10.3389/fcell.2023.1132905.