Over the course of the last several years, the importance of the microbiome has been revealed. Housing the vast majority of our body’s immune system, our gastrointestinal tract plays an essential role of health. Notably, the bacteria lining our intestinal tract, referred to as our microbiome, affects the health we often enjoy. But at the same time, so do the cells that line our intestines. These cells, which can also vary significantly from one person to the next, also influence health and wellness. Thus, expanding our perspective beyond the microbiome toward intestinal cell function is critical in efforts to better understand gut health.
(Read more about the relationship between gut health and heart health in this Bold story.)
With that in mind, researchers have now taken the first steps toward comprehensive intestinal tract mapping. Through novel experimental techniques, they have characterized intestinal cell function based on the gene expressions. In the process, it has become readily apparent that various intestinal cells have an array of responsibilities. In fact, these functions are much more elaborate that previously recognized. While intestinal tract mapping may still have a long way to go, these initial findings are impressive. The results give the first glimpse of just how complex and integrated intestinal cell function truly is.
“The picture we get from each cell is a mosaic of all the different types of genes the cells make and this complement of genes creates a ‘signature’ to tell us what kind of cell it is and potentially what it is doing.” – Scott Magness, PhD., University of North Carolina School of Medicine
New Techniques in Intestinal Tract Mapping
In the past, intestinal tract mapping has been extremely challenging. Scientists were primarily limited to small pieces of tissue collected via biopsies in their studies. Given the massive length of the entire gut, figuring out intestinal cell function from end to end was nearly impossible. However, the researchers at the University of North Carolina School of Medicine took a different approach. They were able to procure the entire intestinal tract of three organ donors for their research. This enabled them to perform intestinal tract mapping in a much more comprehensive manner. Rather than examining individual trees in isolation, they enjoyed the larger context of the forest.
The researchers only examined the epithelial cell lining of the donor’s tissues when performing their intestinal tract mapping. Once isolated, enzymes were then applied to the tissues that broke everything down into individual cells. They then used RNA sequencing techniques to determine which genes each cell expressed. Based on these patterns of gene expression, a “gene signature” was identified for a variety of different cell types. Overall, the researchers were able to categorize 25 different cell types according to presumed intestinal cell function. This was the first time anything like this has ever been performed.
While this process may sound quite simple and straightforward, in reality it was far from it. For instance, there are more than 20,000 genes within a cell that might be turned on or off based in intestinal cell function. Likewise, in their research, each intestinal cell typically had about 11,000 gene products expressed. Out of the nearly 13,000 cells examined, this meant there were over 140 million data points to consider. Fortunately, the researchers were able to use advanced computational techniques to make sense of these large amount of data. This is what allowed them to obtain a much more detailed intestinal tract mapping than previous efforts.
“As far as we know, we’re the first to do this kind of analysis across the length of the human gut from three full donors.” – Jarrett Bliton, Graduate Student, University of North Carolina School of Medicine
Intestinal Cell Function Groups
In the process of intestinal tract mapping, several important cell types were noted based on genes expressed. Some were involved in absorbing nutrients while others absorbed water. Several cell types produced intestinal mucus, which can vary depending on the desired response. Others, such as enteroendocrine cells, produced hormones that affected eating behaviors and intestinal motility. And several were involved in immune system function that included protection from parasitic invasion. Based on the evidence, it was apparent that intestinal cell function was quite varied. Likewise, different portions of the intestinal tract showed different groupings as functions changed.
In addition to these findings, the researchers also noted that various intestinal cells also had different sensors and receptors. One cell type in particular was quite intriguing. These cells, known as tuft cells because of their hair-like projections, were compared to taste buds. The intestinal cell function they served involved detection of potential parasites through their sensory tufts. If a nasty parasite was detected, these cells signaled the immune system to attack. At the same time, other cells had receptors that might explain unwanted side effects from medications. For example, drugs that target inflammatory cells in the intestine work at a specific receptor. But the researchers found that many other cells had these receptors expressed as well. This may explain why so many drugs trigger nausea, vomiting, and other negative gastrointestinal side effects.
“We can see the different sets of genes turned on or off in individual cells. This is how, for instance, we might begin to understand why some people form toxicity to certain foods or drugs and some people don’t.” Joseph Burclaff, PhD., Postdoctoral Fellow, University of North Carolina School of Medicine
Cellular Mapping, Big Data, and Personalized Medicine
The findings that these researchers have revealed about intestinal cell function are quite noteworthy. They demonstrate just how complex and intriguing the intestinal system is. But their intestinal tract mapping also highlights another important issue. Their ability to examine systems at a cellular level invites an entirely new era of personalized medicine. At the same time, their research shows how Big Data in healthcare can further these efforts as well. Without question, there is much more to learn about the microbiome and intestinal cell function. But the results of this most recent study suggests major discoveries are likely to be around the corner.
