Oral microbiome interactions with gingival gene expression patterns for apoptosis, autophagy and hypoxia pathways in progressing periodontitis

Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Octavio A. Gonzalez

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Oral mucosal tissues must react with and respond to microbes comprising the oral microbiome ecology. This study examined the interaction of the microbiome with transcriptomic footprints of apoptosis, autophagy and hypoxia pathways during periodontitis. Adult Macaca mulatta (n = 18; 12–23 years of age) exhibiting a healthy periodontium at baseline were used to induce progressing periodontitis through ligature placement around premolar/molar teeth. Gingival tissue samples collected at baseline, 0·5, 1 and 3 months of disease and at 5 months for disease resolution were analysed via microarray. Bacterial samples were collected at identical sites to the host tissues and analysed using MiSeq. Significant changes in apoptosis and hypoxia gene expression occurred with initiation of disease, while autophagy gene changes generally emerged later in disease progression samples. These interlinked pathways contributing to cellular homeostasis showed significant correlations between altered gene expression profiles in apoptosis, autophagy and hypoxia with groups of genes correlated in different directions across health and disease samples. Bacterial complexes were identified that correlated significantly with profiles of host genes in health, disease and resolution for each pathway. These relationships were more robust in health and resolution samples, with less bacterial complex diversity during disease. Using these pathways as cellular responses to stress in the local periodontal environment, the data are consistent with the concept of dysbiosis at the functional genomics level. It appears that the same bacteria in a healthy microbiome may be interfacing with host cells differently than in a disease lesion site and contributing to the tissue destructive processes.

Original languageEnglish
Pages (from-to)405-417
Number of pages13
Issue number4
StatePublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2020 John Wiley & Sons Ltd


  • apoptosis
  • autophagy
  • hypoxia
  • nonhuman primate
  • periodontitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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