Microbial β-glucuronidases drive human periodontal disease etiology

Lietzan, Adam D.; Simpson, Joshua B.; Walton, William G.; Jariwala, Parth B.; Xu, Yongmei; Boynton, Marcella H.; Liu, Jian; Redinbo, Matthew R.

doi:10.1126/sciadv.adg3390

Microbial β-glucuronidases drive human periodontal disease etiology

Journal Article · Fri May 05 00:00:00 EDT 2023 · Science Advances

DOI:https://doi.org/10.1126/sciadv.adg3390· OSTI ID:2470040

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University of North Carolina, Chapel Hill, NC (United States)

Periodontitis is a chronic inflammatory disease associated with persistent oral microbial dysbiosis. The human β-glucuronidase (GUS) degrades constituents of the periodontium and is used as a biomarker for periodontitis severity. However, the human microbiome also encodes GUS enzymes, and the role of these factors in periodontal disease is poorly understood. Here, we define the 53 unique GUSs in the human oral microbiome and examine diverse GUS orthologs from periodontitis-associated pathogens. Oral bacterial GUS enzymes are more efficient polysaccharide degraders and processers of biomarker substrates than the human enzyme, particularly at pHs associated with disease progression. Using a microbial GUS-selective inhibitor, we show that GUS activity is reduced in clinical samples obtained from individuals with untreated periodontitis and that the degree of inhibition correlates with disease severity. Together, these results establish oral GUS activity as a biomarker that captures both host and microbial contributions to periodontitis, facilitating more efficient clinical monitoring and treatment paradigms for this common inflammatory disease.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470040

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 18 Vol. 9; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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