Study provides insights on mucin degradation mechanisms by a group of gut bacteria

Recent research identified that a single sulfatase adds to the degradation of mucus that safeguards the intestinal lining, resulting in colorectal cancer and inflammatory bowel disease (IBD). The research was published in the journal Nature.

Inflammatory Bowel Disease

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The gut microbiota in humans affects various aspects of intestinal health and disease, like colorectal cancer and inflammatory bowel disease. The secreted mucus in the colon generates a barrier that sets apart gut microbes from the lining of the intestine, hindering close contact that may result in the above-mentioned conditions.

Certain gut bacteria are capable of using mucin glycoproteins—the key mucus component—as a nutrient source. But it is still unclear which bacterial enzymes commence the degradation of the complex O-glycans present in mucins.

In spite of the crucial roles of sulfatases in different biological mechanisms, including diseases, the scientists from a group of universities, which included the University of Liverpool, University of Gothenburg, and the University of Michigan, intended to approach the substantial knowledge gap concerning their mechanisms and specificity.

Mucin 2, a glycoprotein, is the key component of colonic mucus. Mucin glycosylation is inconstant along the gastrointestinal tract, with a rise in sulfation in the colon, particularly in the distal colon.

Certain human gut bacteria have formed complex arsenals of degradative enzymes that include sulfatases to break down the complex O-glycans present in mucins.

Scientists characterized the activity of 12 different sulfatases and demonstrated that sulfatases are vital to the utilization of distal colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron.

The research illustrated that B. thetaiotaomicron has a strong capability to grow on highly sulfated colonic mucin. The study also showed that it has sulfatases proficient in eliminating sulfate groups in all contexts known to occur in mucin. The scientists remarkably identified that a single major sulfatase is disproportionately crucial for growth on colonic mucin O-glycans.

The observations support a vital role for active sulfatases in both normal colonization and inflammation. As mucin glycan structures might differ between mammalian hosts, these vital steps may need to be validated in humans.

The results provide vital information for future studies into blocking this complex enzyme pathway and possibly blocking mucin-degrading activities in bacteria that contribute to diseases like IBD.

Source:
Journal reference:

Luis, A. S., et al. (2021) A single sulfatase is required to access colonic mucin by a gut bacterium. Nature. doi.org/10.1038/s41586-021-03967-5.

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