Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates

Zaramela, Livia S.; Martino, Cameron; Alisson-Silva, Frederico; Rees, Steven D.; Diaz, Sandra L.; Chuzel, Léa; Ganatra, Mehul B.; Taron, Christopher H.; Secrest, Patrick; Zuñiga, Cristal; Huang, Jianbo; Siegel, Dionicio; Chang, Geoffrey; Varki, Ajit; Zengler, Karsten

doi:10.1038/s41564-019-0564-9

Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates

Journal Article · Mon Sep 23 00:00:00 EDT 2019 · Nature Microbiology

DOI:https://doi.org/10.1038/s41564-019-0564-9· OSTI ID:1600797

^[1]; ^[1]; ^[1]; ^[1]; Diaz, Sandra L. ^[1]; Chuzel, Léa ^[2]; Ganatra, Mehul B. ^[2]; Taron, Christopher H. ^[2]; Secrest, Patrick ^[1]; ^[1]; Huang, Jianbo ^[1]; Siegel, Dionicio ^[1]; Chang, Geoffrey ^[1]; ^[1]; ^[1]

Univ. of California, San Diego, CA (United States)
New England Biolabs, Ipswich, MA (United States)

Dietary habits have been associated with alterations of the human gut resident microorganisms contributing to obesity, diabetes and cancer. In Western diets, red meat is a frequently eaten food, but long-term consumption has been associated with increased risk of disease. Red meat is enriched in N-glycolylneuraminic acid (Neu5Gc) that cannot be synthesized by humans. However, consumption can cause Neu5Gc incorporation into cell surface glycans, especially in carcinomas. As a consequence, an inflammatory response is triggered when Neu5Gc-containing glycans encounter circulating anti-Neu5Gc antibodies. Although bacteria can use free sialic acids as a nutrient source, it is currently unknown if gut microorganisms contribute to releasing Neu5Gc from food. Iin this work, we found that a Neu5Gc-rich diet induces changes in the gut microbiota, with Bacteroidales and Clostridiales responding the most. Genome assembling of mouse and human shotgun metagenomic sequencing identified bacterial sialidases with previously unobserved substrate preference for Neu5Gc-containing glycans. X-ray crystallography revealed key amino acids potentially contributing to substrate preference. Additionally, we verified that mouse and human sialidases were able to release Neu5Gc from red meat. The release of Neu5Gc from red meat using bacterial sialidases could reduce the risk of inflammatory diseases associated with red meat consumption, including colorectal cancer and atherosclerosis.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); Program Science Without Borders Bex; USDOE Office of Science (SC)

OSTI ID:: 1600797

Journal Information:: Nature Microbiology, Journal Name: Nature Microbiology Journal Issue: 12 Vol. 4; ISSN 2058-5276

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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