ArticlemBio2025
SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx.
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Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3citing papers in PubMed
–field-weighted citation impact
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Who cites it
3 citing papers in PubMed.
- Novel chemistry and structural perspectives in vitamin BChemical science · 2026Review
- Role and Mechanisms of Gut Microbiota in Infectious Diseases: Recent Evidence from Animal Models.Biology · 2026Review
- Longitudinal multi-omic dynamics in hospitalized COVID-19 patients based on disease severity.Gut microbes reports · 2026Article
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Authors and funding
65 authors.
Cameron Martino *Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0001-9334-1258
Benjamin P Kellman *Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Daniel R Sandoval *Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.
Thomas Mandel Clausen *Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.
Robert CooperDepartment of Bioengineering, University of California San Diego, La Jolla, California, USA.
Alhosna BenjdiaUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France.
Feryel SoualmiaUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France.
Alex E ClarkDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Aaron F GarretsonDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Clarisse A MarotzDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Se Jin SongCenter for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
Stephen WandroCenter for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
Livia S ZaramelaDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Rodolfo A SalidoDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0003-0631-2817
Qiyun ZhuDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Erick ArmingolDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Yoshiki Vázquez-BaezaCenter for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
Daniel McDonaldDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
James T SorrentinoDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Bryn TaylorBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA.ORCID 0000-0002-4957-5417
Pedro Belda-FerreDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Promi DasDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0001-6733-2059
Farhana AliDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Chenguang LiangDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Yujie ZhangDepartment of Bioengineering, University of California San Diego, La Jolla, California, USA.
Luca SchifanellaDepartment of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Alice CovizziDepartment of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy.
Alessia LaiDepartment of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy.
Agostino RivaDepartment of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy.
Christopher BastingDepartment of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Courtney Ann BroedlowDepartment of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Aki S HavulinnaDepartment of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland.
Pekka JousilahtiDepartment of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland.
Mehrbod EstakiDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0003-4556-8444
Tomasz KosciolekDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Rayus KuplickiLaureate Institute for Brain Research, Tulsa, Oklahoma, USA.
Teresa A VictorLaureate Institute for Brain Research, Tulsa, Oklahoma, USA.
Martin P PaulusLaureate Institute for Brain Research, Tulsa, Oklahoma, USA.
Kristen E SavageDivision of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.
Jennifer L BenbowDivision of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.
Emma S SpielfogelDivision of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.
Cheryl A M AndersonHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
Maria Elena MartinezHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
James V LaceyDivision of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.
Shi HuangDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Niina HaiminenIBM T. J. Watson Research Center, Yorktown Heights, New York, USA.ORCID 0000-0002-8663-1019
Laxmi ParidaIBM T. J. Watson Research Center, Yorktown Heights, New York, USA.
Ho-Cheol KimAI and Cognitive Software, IBM Research-Almaden, San Jose, California, USA.
Jack A GilbertDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Daniel A SweeneyDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Sarah M AllardDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Austin D SwaffordCenter for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.ORCID 0000-0001-5655-8300
Susan ChengDivision of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Michael InouyeHealth Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom.
Teemu NiiranenDepartment of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland.
Mohit JainDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Veikko SalomaaDepartment of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland.
Karsten ZenglerDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0002-8062-3296
Nichole R KlattDepartment of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0003-2968-5480
Jeff HastyDepartment of Bioengineering, University of California San Diego, La Jolla, California, USA.
Olivier BerteauUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France.
Aaron F CarlinDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Jeffrey D Esko *Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.
Nathan E Lewis *Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Rob Knight *Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0002-0975-9019
Funding
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9MTransgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3MCALIFORNIA TEACHERS STUDYR01CA077398 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BERNSTEIN, LESLIE · 1998 to 2014
$29.7MProtein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ESKO, JEFFREY D · 2016 to 2025
$26.2MOil and Gas as Drivers of Climate Change and Health: Developing unique resources to investigate multi-level and diverse effects of exposure to oil and gas wellsU01CA199277 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LACEY, JAMES V, MARTINEZ, MARIA ELENA · 2015 to 2024
$20.7MEngineered Gene Circuits for Basic Science and BiotechnologyR01GM069811 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, TSIMRING, LEV S · 2004 to 2025
$13.6MNovel Platforms for Human Intestinal Enteroids: Matrix, Mechanics, and TopographyU19AI116497 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI MARESSO, ANTHONY W · 2015 to 2025
$13.2MSan Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8MNew Biospecimens to Enhance Research in the California Teachers Study CohortUM1CA164917 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LACEY, JAMES V · 2012 to 2015
$10.1MMapping host-microbe-metabolite interactions in 3D to find diet-derived enhancers of immunityDP1AT010885 · NCCIH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KNIGHT, ROB · 2019 to 2023
$5.5MUnraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3MMapping the Plasma Exposome and its Association with Human Cardiovascular DiseaseR01ES027595 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2017 to 2021
$3.3MAcademy of Finland 321351 and 354447Academy of Finland 321356Academy of Finland 335525Alfred Benzon Foundation (The Alfred Benzon Foundation)ANID Becas Chile Doctorado 2018-72190270British Heart Foundation (BHF) RG/13/13/30194British Heart Foundation (BHF) RG/18/13/33946Emerald Foundation 3022Emil Aaltosen Säätiö (Emil Aaltonen Foundation)French National Research Agency ANR-17-CE11-0014French National Research Agency ANR-20-CE44-0005Health Data Research UK (HDR UK)HHS | National Institutes of Health (NIH) 1DP1AT010885HHS | National Institutes of Health (NIH) 1P30DK120515HHS | National Institutes of Health (NIH) P30-CA023100HHS | National Institutes of Health (NIH) P30-CA033572HHS | National Institutes of Health (NIH) R01-CA077398HHS | National Institutes of Health (NIH) R01ES027595HHS | National Institutes of Health (NIH) R01GM069811HHS | National Institutes of Health (NIH) R35GM119850HHS | National Institutes of Health (NIH) U01-CA199277HHS | National Institutes of Health (NIH) UH2AI153029HHS | National Institutes of Health (NIH) UM1-CA164917IBM | IBM Research AI Horizons NetworkMunz Chair of Cardiovascular Prediction and PreventionNational Science Foundation (NSF) 2031989National Science Foundation (NSF) 2038509NCCIH NIH HHS DP1 AT010885NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA077398NCI NIH HHS U01 CA199277NCI NIH HHS UM1 CA164917NHLBI NIH HHS P01 HL131474NIAID NIH HHS U19 AI116497NIAID NIH HHS UH2 AI153029NIDDK NIH HHS P30 DK120515NIEHS NIH HHS R01 ES027595NIGMS NIH HHS R01 GM069811NIGMS NIH HHS R35 GM119850NIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)NIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC) BRC-1215-20014Novo Nordisk Foundation NNF20SA0066621Sydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research)UC San Diego Center for Microbiome Innovation N/AUC | University of California, San Diego (UCSD) R00RG2503Union's Horizon Europe Research and Innovation 459 Actions 101046041Wellcome Trust
Abstract
The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity
Indexed as
BacteriaCOVID-19Gastrointestinal MicrobiomeGlycocalyxSARS-CoV-2AdultFemaleGastrointestinal TractHeparan Sulfate ProteoglycansHumansMaleMiddle AgedSpike Glycoprotein, CoronavirusHeparan Sulfate ProteoglycansSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2agingCovidHeparan Sulfatehuman microbiomeSARS-CoV-2
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