Determining bacterial and host contributions to the human salivary metabolome

Abstract

Background: Salivary metabolomics is rapidly advancing. Aim and methods: To determine the extent to which salivary metabolites reflects host or microbial metabolic activity whole-mouth saliva (WMS), parotid saliva (PS) and plasma collected contemporaneously from healthy volunteers were analysed by 1 H-NMR spectroscopy. Spectra underwent principal component analysis and k-means cluster analysis and metabolite quantification. WMS samples were cultured on both sucrose and peptide-enriched media. Correlation between metabolite concentration and bacterial load was assessed. Results: WMS contained abundant short-chain fatty acids (SCFAs), which were minimal in PS and plasma. WMS spectral exhibited greater inter-individual variation than those of PS or plasma (6.7 and 3.6 fold, respectively), likely reflecting diversity of microbial metabolomes. WMS bacterial load correlated strongly with SCFA levels. Additional WMS metabolites including amines, amino acids and organic acids were positively correlated with bacterial load. Lactate, urea and citrate appeared to enter WMS via PS and the circulation. Urea correlated inversely with WMS bacterial load. Conclusions: Oral microbiota contribute significantly to the WMS metabolome. Several WMS metabolites (lactate, urea and citrate) are derived from the host circulation. WMS may be particularly useful to aid diagnosis of conditions reflective of dysbiosis. WMS could also complement other gastrointestinal fluids in future metabolomic studies. ARTICLE HISTORY

Salivary Metabolomics: From Diagnostic Biomarker Discovery to Investigating Biological Function

“…This was demonstrated by comparison of sterile parotid gland saliva with WMS, which reveals that prior to entering the oral cavity, glandular saliva is devoid of many WMS metabolites such as acetate, butyrate and propionate, collectively known as short-chain fatty acids (SCFAs). Furthermore, the concentration of many WMS metabolites including SCFAs, amines, phenylalanine, glycine, and succinate correlate strongly with the bacterial load in WMS [95]. Such a finding has significant implications for the diagnostic utility of these metabolites, as highlighted in the previous section, as certain metabolites that have been identified as putative biomarkers may be reflective of changes in the oral microbiome.…”

“…Host-derived salivary metabolites include lactate, citrate, and urea. Urea has been shown to negatively correlate with salivary bacterial load as well as dental plaque as it is utilized by oral bacteria [60,95]. Previous metabolomic study of PS has been complicated by low spectral resolution or low number of donors [20,96].…”

“…Taurine is present at high concentrations in GCF and is likely concentrated via immune cells which have been shown to be capable of concentrating up to 50 mM taurine [98]. Samples were collected and spectra were acquired on separate occasions as previously described [95]. Spectra are scaled to the lactate peak to assess relative metabolite concentrations.…”

Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

“…However, human microbiome research requires integration with other omic approaches to advance microbiome-based interventions for health and disease management. Pairing metabolomics with metagenomics is now becoming a very promising approach for the identification of complex bacterial metabolic functions, leading towards the development of therapeutic strategies for manipulation of the microbial metabolism in those at risk of disease development [20][21][22]. Taxonomic shifts triggered by different physiological and pathological conditions could modify interactions between microbial community members.…”

“…Given that many metabolites and metabolic pathways are relatively conserved across species, the coupling of two omics approaches provides insights into the association of the human microbiome with health status and risk of disease development [19]. Much work has been done to explore a complex interplay between host-microbiome and metabolome in the gut [20], cervix [21], and saliva [22]. Indeed a recent multi-omic integration study revealed that mainly amino acids and amino acid degradation products, such as polyamines, were well-predicted to be modulated by cervical microorganisms [21].…”