Gut Enzymes Show Promise in Helping to Identify Potential Diseases

 

According to a study published in Nature Communications on August 11, enzymes that are used by bacteria to break down mucus in the gut can potentially be useful biomarkers for intestinal diseases.

These conclusions were drawn by researchers from the University of Birmingham and Newcastle University, who were able to successfully identify and characterize one of the key enzymes in the process. In their experimentation, they showed how the enzyme enables bacteria to break down and feed off sugars in layers of mucus within the gut.

Now, the researchers believe that this mechanism may be able to be used for the diagnosis of intestinal diseases.

Mucin, or the molecules in mucus, are constantly produced to generate the layer of mucus within the gut that acts as a barrier between bacteria and the rest of the body. In addition, mucin contains chains of sugar molecules called glycans, which can provide nutrients for the bacteria.

In their experimentation, the researchers looked at how this enzyme reacts with mucin. Glycans are known to change when certain diseases exist within the body. For this reason, the study authors believe that it may be possible to use the enzymes to take a “snapshot” of glycans and potentially identify diseases.

“Mucus is structured a bit like a tree, with lots of different branches and leaves,” said lead researcher Dr. Lucy Crouch of the University of Birmingham’s School of Biosciences. “Lots of the enzymes discovered so far might clip away some of the leaves to eat, but the enzyme we studied will clip away a whole branch — that’s quite a distinctive mechanism and it gives us a useful biomarker for studying disease.”

In the study, the researchers observed this process in three different diseases. They looked at tissue from adults with ulcerative colitis and colorectal cancer, and from preterm infants with necrotizing enterocolitis. When they added the enzyme to the samples and labeled the glycans with a fluorescent dye, they were able to gain insight into the glycan structures.

“Although we still don’t fully understand what the glycan structures are made from and how these vary between different tissue types, we can see that the differences in structure between health and non-healthy tissue is quite distinctive,” Dr. Crouch added. “We hope to be able to use these enzymes to start producing better diagnostics for the very early stages of these diseases.”

Gut enzymes not only play a role in disease, but the chronic inflammation associated with human aging as well. Back in March, researchers published a study in JCI Insight that showed how gut-barrier dysfunction and gut-derived chronic inflammation impact aging.

By studying mice and fruit flies, researchers discovered that the enzyme intestinal alkaline phosphatase (IAP) can potentially prevent intestinal permeability and gut-derived systemic inflammation. They believe this can result in less frailty and an extended lifespan in humans.

“Oral IAP supplementation in older mice significantly preserved gut barrier function and was associated with preserving the homeostasis of the gut microbiota during aging,” said Richard Hodin, MD, chief of the Division of General and Gastrointestinal Surgery at Massachusetts General Hospital. “In other words, the enzyme maintained the composition of the gut bacteria and controlled the low-grade chronic inflammation that can happen with aging.”

IAP is a naturally occurring enzyme that almost entirely remains in the gut of humans. However, Hodin believes that it is likely nontoxic, and those who show low levels as they age may be able to supplement.