According to a new study published in Nature, a single sulfatase enzyme leads to the degradation of mucus that protects the intestinal lining, eventually leading to inflammatory bowel disease (IBD) and colorectal cancer.

Several aspects of intestinal health and disease, including inflammatory bowel disease and colorectal cancer, are profoundly influenced by the human gut microbiota. Secreted mucus in the colon forms a barrier between gut microbes and the lining of the intestine, limiting close contact that can contribute to various disorders.

Mucin glycoproteins, the major component of mucus, can be used as a nutrition source by some gut bacteria. However, it is unknown which bacterial enzymes trigger the breakdown of the complex O-glycans found in mucins.

Despite the importance of sulfatases in many biological processes, including disease, the researchers from a consortium of universities, including the University of Liverpool, the University of Gothenburg, and the University of Michigan, aimed to fill a significant knowledge gap about their specificity and mechanisms.

Mucin 2, a glycoprotein, is a key component of intestinal mucus. Mucin glycosylation varies along the gastrointestinal tract, with sulfation increasing in the colon, particularly in the distal colon.

To digest the complex O-glycans found in mucins, some human gut bacteria have evolved complicated arsenals of degradative enzymes, including sulfatases.

Researchers were able to demonstrate that sulfatases are required for the consumption of distal colonic mucin O-glycans by the human gut commensal Bacteroides thetaiotaomicron by analyzing the activity of 12 distinct sulfatases.

According to the findings, B. thetaiotaomicron has a strong ability to grow on highly sulfated colonic mucus and sulfatases capable of eliminating sulfate groups in all settings where they are known to occur in mucin. Surprisingly, researchers discovered that a single critical sulfatase has a disproportionate role in colonic mucin O-glycan development.

The data suggest that active sulfatases play an important role in both normal colonization and inflammation.

Given that mucin glycan structures differ amongst mammalian hosts, these crucial processes may need to be confirmed in humans.

These findings will help guide future research into preventing this complex enzyme pathway and perhaps limiting mucin-degrading activities in bacteria that cause diseases like IBD.

Source: Nature, DOI: 10.1038/s41586-021-03967-5

Image Credit: Getty

You were reading: A potential drug target for IBD and colorectal cancer