Eleftheria Charalambous

Early-life adversity leaves long-lasting taxonomic and metabolic imprints on the Oral Microbiome

At birth, the microbiome is seeded by birth route and its composition evolves over the first 1000 days
of life. Tissue-specific microbiota are establish with distinctive abundance, diversity, and resilience.
Key player for its development is the early exposome which also impacts the overall health trajectory
via effects on multisystem development. This is also associated with a pro-inflammatory and
immunosenescent phenotype observed in later life. Our study investigates the role of the oral
microbiome and microbial metabolism in an early-life adversity model.
We performed 16S V4 amplicon sequencing on microbial DNA from Saliva and buccal samples from
the EpiPath cohort. This is a cohort of 115 adults, mean age 24, who either experienced
institutionalisation and adoption (n=40) or were non-adopted controls (n=75). Taxonomic analyses
performed using mothur and metabolic modelling of the oral microbiome accomplished with
constraint-based reconstruction and analysis (COBRA) in Matlab. Data analysis, integration and
visualisation were performed with R and STATA.
We identified multiple significant taxonomic associations between adoptees and non-adopted
controls, lifestyle covariates and immunophenotypic markers. Five taxa were significantly reduced in
the adoptees (FDR<0.05). Eight genera associate with total number of NK cells and activated NK cells
as well as and CD57+CD4+ senescent T cells (FDR<0.05). Ten genera associate with prior
herpesviridiae infection (FDR<0.05).Metabolic reconstructions identified global differences in the oral
microbiome metabolic profile after exposure to adversity (FDR<0.05). Furthermore, we identified a
series of 40 differentially secreted or absorbed metabolites, that associated with adversity, age of
adoption, prior herpesviridiae infection, circulating numbers and activation status of NK cells and T
cells (FDR<0.05).

Our data expose adversity imprints on both the salivary and buccal oral microbial compositions as
well as their metabolic capacity that remain identifiable in early adulthood. Metabolic and
compositional associations that we demonstrated here suggest a complex web of mechanisms that
clearly incorporate NK cell activity and immunosenescence with a prior adverse experience,
mediated by the microbiome. The challenge remains to identify how this interwoven series of
changes exert a lifelong influence that eventually manifests as an increased risk of disease.
Keywords: #microbiome #metabolicmodeling #adversity #immunology #immunesystem

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