Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation
Abstract
Saccharibacteria (TM7) are obligate epibionts living on the surface of their host bacteria and are strongly correlated with dysbiotic microbiomes during periodontitis and other inflammatory diseases, suggesting they are putative pathogens. However, due to the recalcitrance of TM7 cultivation, causal research to investigate their role in inflammatory diseases is lacking. Here, we isolated multiple TM7 species on their host bacteria from periodontitis patients. These TM7 species reduce inflammation and consequential bone loss by modulating host bacterial pathogenicity in a mouse ligature-induced periodontitis model. Two host bacterial functions involved in collagen binding and utilization of eukaryotic sialic acid are required for inducing bone loss and are altered by TM7 association. This TM7-mediated downregulation of host bacterial pathogenicity is shown for multiple TM7/host bacteria pairs, suggesting that, in contrast to their suspected pathogenic role, TM7 could protect mammalian hosts from inflammatory damage induced by their host bacteria.
Additional Information
© 2021 Elsevier Inc. Received 15 July 2021, Revised 23 August 2021, Accepted 16 September 2021, Available online 11 October 2021. We thank Xiaozhe Han and Yufeng Wang for ligature training; Alpdogan Kantarci, Thomas Van Dyke, and Ning Yu for productive discussion on immunology; Floyd Dewhirst and Mircea Podar for host bacterial strains. We also thank Jennifer Gundrum and Tabita Ramirez-Puebla for fluorescence imaging. We were supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under awards 1R01DE023810, 1R01DE020102, 1R01DE026186 (to X.H., and J.S.M.); F31DE026057 (to J.K.B.); and 1K99DE027719-01 (to B.B.). Additional support was provided to D.R.U. by the National Science Foundation Graduate Research Fellowship Program under grant DGE1745303 (to D.R.U.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NSF. Preliminary studies were supported by the Forsyth Institute Pilot Grant Program. Data and code availability: The raw sequencing data and original code generated by this study were deposited on Mendeley Data: https://doi.org/10.17632/vp68zv9wj9.1, with the exception of initial 32 patient 16S rRNA sequencing data. These data were collected as a confidential medical record at Forsyth Center for Clinical and Translational Research, and we cannot release the raw data publicly due to ethical prohibition. Individuals who are interested in these data can contact the Lead Contact. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the database identifiers: PXD026999 and 10.6019/PXD026999. Please see detailed discriptions of the data collection and analysis in STAR methods. Author contributions: Conceptualization, J.S.M., X.H., D.R.U., and B.B.; methodology, O.C., D.R.U., J.K.B., Y.M., F.S., Y.A., M.H., F.B., H.H., J.S.M., X.H., and B.B.; investigation, O.C., D.R.U., J.K.B., Y.M., F.S., G.M., Y.A., H.H., J.S.M., and B.B.; formal analysis, O.C., D.R.U., J.K.B., F.S., D.C., Y.A., F.B., M.H., J.S.M., X.H., and B.B.; writing – original draft, O.C., D.R.U., J.S.M., X.H., and B.B.; data curation, D.R.U., F.S., M.H., Y.A., H.H., and J.S.M.; writing – review & editing, all authors; project administration and funding acquisition, B.B., J.S., and X.H.; resources O.C., D.R.U., J.K.B., D.C., Y.M., F.S., Y.A., H.H., J.S.M., X.H., and B.B. The authors declare no competing interests.Attached Files
Accepted Version - nihms-1743587.pdf
Supplemental Material - 1-s2.0-S193131282100425X-mmc1.pdf
Supplemental Material - 1-s2.0-S193131282100425X-mmc2.xlsx
Files
Additional details
- PMCID
- PMC8595704
- Eprint ID
- 111605
- Resolver ID
- CaltechAUTHORS:20211022-170856506
- 1R01DE023810
- NIH
- 1R01DE020102
- NIH
- 1R01DE026186
- NIH
- F31DE026057
- NIH Postdoctoral Fellowship
- 1K99DE027719-01
- NIH
- DGE-1745303
- NSF Graduate Research Fellowship
- Created
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2021-10-23Created from EPrint's datestamp field
- Updated
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2023-07-07Created from EPrint's last_modified field