gut mucins

Sulfated glycans are a major structural and functional component of the human gut. In the colon, a secreted mucus layer coats the intestinal epithelium and forms a protective barrier between the host and the gut microbiota. This mucus layer is composed largely of glycans, many of which are sulfated.

Each glycan's precise chemical structure determines how it is recognised and processed by gut microbes. Sulfation patterns can protect mucin glycans from degradation, whereas removal of sulfate groups enables microbial enzymes to access and metabolise these sugars. Controlled glycan turnover supports gut homeostasis, but excessive mucin degradation disrupts the barrier and is associated with inflammation and disease.

Our research uses medicinal chemistry and chemical biology to understand how gut microbes interact with host glycans. We focus on bacterial glycan sulfatases, specialised enzymes that regulate access to sulfated mucin glycans and act as key control points in microbial metabolism.

Selected Publications

  1. Luis, A. S. et al. A Single Sulfatase Is Required to Access Colonic Mucin by a Gut Bacterium.
    Nature 2021, 598 (7880), 332–337.
  2. Luis, A. S. et al. Sulfated Glycan Recognition by Carbohydrate Sulfatases of the Human Gut Microbiota.
    Nat. Chem. Biol. 2022, 18 (8), 841–849.
  3. Crawford, C. J. et al. Arylsulfamates Inhibit Colonic Bacteroidota Growth Through a Sulfatase-Independent Mechanism.
    Proc. Natl. Acad. Sci. U.S.A. 2025, 122 (28).
  4. Hanson, S. R. et al. Sulfatases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility.
    Angew. Chem. Int. Ed. Engl. 2004, 43 (43), 5736–5763.
  5. Chiu, L. T. et al. Trisaccharide Sulfate and Its Sulfonamide as an Effective Substrate and Inhibitor of Human Endo-O-Sulfatase-1.
    J. Am. Chem. Soc. 2020, 142 (11), 5282–5292.
  6. Smith, E. L. et al. An Expanded Set of Fluorogenic Sulfatase Activity Probes.
    ChemBioChem 2014, 15 (8), 1101–1105.