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A New Approach to Crohn’s Disease, IBS and Leaky Gut

A PhD Student Investigates The Intricate Details Involved in Gut Health and Disease

July 31, 2023 Kimbra Cutlip

Hammed Ayansola is a firm believer that gut health equals good health. But he also knows that for people with chronic conditions like Crohn’s disease and ulcerative colitis, gut health takes more than a good diet. As a PhD student in the Department of Animal and Avian Sciences, Ayansola is teasing apart the complex mechanisms involved in healing a damaged intestinal tract.

His goal is to understand the chemical signals that certain cells in the intestines send to one another, and how those signals trigger different steps in the gut healing process. He is specifically focused on the interactions between two types of cells that exist throughout the body–in our skin, our organs, bones and connective tissues: Mesenchymal stem cells are able to differentiate into a variety of mature cell types like cartilage, bone, fat cells, and muscles, and promote wound healing after injury.

Epithelial cells, meanwhile, line various tissues and organs in our body, including the lining of the intestines. These are the cells that become weakened and injured with chronic inflammatory diseases like irritable bowel syndrome and Crohn’s disease.

“When we talk of the intestine, you know it's one of the most important tissues in the body, because it's a kind of gateway to all of the other tissues in the body, and it creates a barrier to prevent harmful substances we might likely absorb into our body system,” Ayansola said. “As intestinal cell biologists, our aim is to understand how the different cells of the intestine interact in a healthy state and in injury.”

To conduct his studies, Ayansola needs mesenchymal cells, but isolating them from the intestines is difficult and raises ethical concerns, which may be partly why the questions he is asking have not yet been answered. With the help of his advisor, Assistant Professor Younggeon Jin, Ayansola is taking an innovative approach to the challenge by using mesenchymal cells from human bone marrow, which are readily available from commercial laboratories. Studies in mice have shown that bone marrow mesenchymal cells can influence immune reactions in bone, liver and fat cells, but no one has looked at their ability to heal human gut tissues.

Ayansola’s first experiments were focused on learning if bone marrow mesenchymal cells would interact directly with the epithelial cells of the intestine, and if so, could they spur healing the way intestinal mesenchymal cells do. If they do, Ayansola will then zero in on how. He will investigate the chemical signals the two types of cells use to communicate with one another, the mechanisms that regulate those signals, and how they lead to healing in the epithelial cells.His findings may help in the development of therapeutics to prevent or cure intestinal diseases.

So far, Ayansola has found that adding bone marrow mesenchymal cells to laboratory-grown, colon-like structures called colonoids increases the number of stem cells, undifferentiated cells that have the potential to become many other kinds of cells. These stem cells can be thought of as soldiers in waiting, ready to jump in and replace other cells that become damaged.

Now that he has shown a clear interaction in normal conditions, Ayansola will study the effect of bone marrow mesenchymal cells on colonoids in low-oxygen environments and with inflammatory immune factors, which mimics an injured gut environment. He expects that those stem-cells in waiting will step up to replace any damaged epithelial cells. If they do, then, he can begin to parse out what chemical signals are exchanged between the different cells to trigger the different steps throughout the process. Perhaps some day, the chemicals he identifies can be used to develop medications for treating intestinal diseases.

Uncovering the mechanisms of illness and healing is a long, slow road, but Ayansola is unfazed by hard work and said he revels in big challenges. To get where he is today, he has had to learn multiple languages and adapt to life in vastly different cultures. After earning a master’s degree in agricultural biochemistry and nutrition at the University of Ibadan in his homeland of Nigeria, he spent a year in China learning the language before pursuing his second master’s degree in animal nutrition and feed science Then he applied to his PhD program at AGNR, and has had to adapt all over again to life in the U.S.

“I love exploring,” Ayansola said, “And when you are an international student, funding has a big impact on your opportunities to explore different countries and cultures. I am privileged to earn such support here at the University of Maryland.”

As for what comes after his PhD, Ayansola said he is confident the future will sort itself out, right now, he is focused on taking one step at a time.