Gut Enzymes Touted as Potential Biomarkers for Intestinal Diseases

Gut Enzymes Touted as Potential Biomarkers for Intestinal Diseases
[Source: Ed Reschke/Getty Images]

Researchers at the University of Birmingham and Newcastle University have identified and characterized key enzymes used by bacteria to break down mucus in the gut, which may be used as a helpful biomarker for intestinal diseases.

Their study, “Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown,” is published in Nature Communications and led by Lucy Crouch, Ph.D., a researcher at Newcastle University.

The molecules in mucus, called mucin, are constantly produced by the body to generate the layer of mucus in the gut that provides a barrier between the gut’s complex populations of bacteria and the rest of the body. Mucin contain chains of sugar molecules called glycans, and these also provide an essential source of nutrients for bacteria.

The researchers demonstrated how glycans enable bacteria to break down and feed off sugars in the layers of mucus lining the gut.

“The thick mucus layer of the gut provides a barrier to infiltration of the underlying epithelia by both the normal microbiota and enteric pathogens. Some members of the microbiota utilize mucin glycoproteins as a nutrient source, but a detailed understanding of the mechanisms used to breakdown these complex macromolecules is lacking. Here we describe the discovery and characterization of endo-acting enzymes from prominent mucin-degrading bacteria that target the polyLacNAc structures within oligosaccharide side chains of both animal and human mucins,” the researchers wrote.

The team investigated how this enzyme sits on the outside of the bacterial cell and clips away parts of the mucin molecule, taking them inside the bacterial cell to be consumed.

Because glycans are known to change when certain diseases are present in the body, the researchers anticipate it will be possible to use the enzymes to take a snapshot of the glycans within a biopsy and use that as a biomarker for early detection of the disease.

Crouch noted, “Mucus is structured a bit like a tree, with lots of different branches and leaves. 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.”

The team has investigated the process in tissue samples of three diseases, ulcerative colitis, colorectal cancer, and necrotizing enterocolitis, a serious illness in which the gut becomes inflamed and can start to die. They observed that by adding the enzyme to the samples and labeling the glycans with a fluorescent dye, they were able to get useful information about the glycan structure.

Crouch added that although they do not fully understand what the glycan structures are made from and how they vary from different tissue types, the differences between healthy and non-healthy tissue types can be seen. The team is looking forward to utilizing the enzymes to provide better diagnostics for the early stages of disease.

Their research opens a door to understanding the complex relationships at work in the gut.  Because the mechanism used by the enzyme is particularly distinctive, the researchers anticipate it can be used in the development of new diagnostics for intestinal diseases.