Metagenomic and Metatranscriptomic Examinations of the Oral Microbiome in Health and Disease

Christopher Dupont, Ph.D.

Special Faculty Recruitment Seminar 

Associate Professor in the Genomic Medicine, Environment & Sustainability, and Synthetic Biology groups

J. Craig Venter Institute

Seminar Information

Seminar Date
April 29, 2022 - 2:00 PM

PFBH FUNG Auditorium and via Zoom

Chris Dupont


Dental caries is one of most common chronic health conditions, affecting nearly 3.5 billion people worldwide to an estimated economic cost of $245 billion. The role of host genetics in structuring the oral microbiome is not clear.   While it is unequivocal that the oral microbiome is responsible for the formation of caries, there are conflicting views about whether it is a single taxa or ecological disease. The diagnosis of caries currently involves direct observation by a professional, indicating a possible need for leading molecular diagnostics. Using 16S, metagenomic, and metatranscriptome surveys of oral plaque sampled from a twins cohort, we addressed each of these issues.  We found that the oral microbiota does include heritable taxa and that the oral microbiome was always more similar in a shared host genotype. An iterative subject-specific metagenomic assembly pipeline generated 658 bacterial, 179 DNA virus, and 10 RNA virus metagenome assembled genomes. Grouping into species level clusters revealed that the Gracillibacteria are highly personalized, while many other taxa such as Cardiobacter are conserved genomically across the entire sample population, which has implications for the development of oral microbiome based forensic approaches. We applied novel feature engineering and compositionally-aware ensemble network frameworks to the integrated metagenomic and metatranscriptomic data. These methods can be applied when hypothesis testing for differential abundance do not capture statistical enrichments or the results from such analysis are not adequate for providing deeper insight into disease. We identified which organisms and metabolic pathways were central in a co-expression network but also how these networks were rewired between caries and caries-free phenotypes. Our findings provide evidence of a core oral microbiome composed of both bacteria and viruses that were transcriptionally active in all participants regardless of phenotype, but also show highly diagnostic changes in the ways that organisms interact. Specifically, many organisms exhibit high connectedness with central carbon metabolism to Cardiobacterium and this shift serves a bridge between phenotypes. Our evidence supports the hypothesis that caries is a multifactorial ecological disease.

Speaker Bio

Chris Dupont is an Associate Professor in the Genomic Medicine, Environment & Sustainability, and Synthetic Biology groups at JCVI. His primary research focus is microbial physiology and the environmental and evolutionary influence on physiological variation. This involves work with model organisms in laboratory systems, synthetic biology domestication of wild microbes for model studies, and sequencing based profiling of microbial communities in a variety of environments, including organismal microbiomes. This includes metagenomic and metatranscriptomic studies of the microbiomes found in the human gut, respiratory pathways, skin, and oral surfaces. Dr. Dupont is also working on applying synthetic biology and machine learning techniques to solve unique problems in big datasets associated with the human microbiome and the environment.

Dr. Dupont began his career at JCVI as a postdoctoral fellow. He received his PhD in Oceanography and Marine Biology from the Scripps Institution of Oceanography, as well as a BS in Natural Resources and a MS of Biological and Environmental Engineering from Cornell University.