. Author manuscript; available in PMC: 2021 Mar 17.

Published in final edited form as: Periodontol 2000. 2020 Feb;82(1):115–128. doi: 10.1111/prd.12316

TABLE 3.

Human metabolomic studies

Reference	Sample type	Periodontal condition	Analysis method	Findings
Chen et al (2018)⁹¹	Gingival crevicular fluid	Generalized aggressive periodontitis	GC-MS	Oxidative stress: increased dehydroascorbic acid, urea, xanthine; decreased glutathione
				Purine degradation: increased xanthine and urea
				Tyrosine metabolism: increased noradrenaline
				Pyrimidine metabolism: increased beta-alanine, uridine, malonate; decreased thymidine
				Bacterial biochemistry: increased ribulose-5-phosphate, glucose-1-phosphate
Garcia-Villaescusa et al (2018)⁹⁹	Saliva	Moderate and severe periodontitis	H-NMR	Early periodontitis: increased lactate-proline, lactate, proline; decreased caprocate, isoleucine, isopropanol, choline
Garcia-Villaescusa et al (2018)⁹⁹	Saliva	Moderate and severe periodontitis	H-NMR	Moderate-severe periodontitis: increased caprocate, isoleucine, isopropanol, choline, isocaprocate + butyrate, isovalerate, 4 aminobutyrate; decreased sucrose, sucrose-glucose-lysine, lactate-proline, lactate, proline
Romano et al (2018)⁹⁴	Saliva	Chronic periodontitis	H-NMR	Chronic periodontitis: decreased pyruvate, N-acetyl groups, lactate; increased tyrosine, valine, isoleucine, phenylalanine, proline
Romano et al (2018)⁹⁴	Saliva	Aggressive periodontitis	H-NMR	Aggressive periodontitis: decreased pyruvate, N-acetyl groups, lactate, sarcosine; increased tyrosine, phenylalanine, formate
Rzeznik et al (2017)⁹⁸	Saliva	Active periodontitis (chronic and aggressive)	H-NMR	Increased butyrate (short-chain fatty acids)
Rzeznik et al (2017)⁹⁸	Saliva	Active periodontitis (chronic and aggressive)	H-NMR	Decreased fucose, lactate, acetate, N-acetyl, gamma aminobutyrate, 3-D-hydroxybutyrate, pyruvate, methanol, threonine, ethanol
Sakanaka et al (2017)⁹⁷	Dental plaque	Low and high PISA (pre- and postdebridement)	GC-MS	High PISA (predebridement): 4 aminobutyric acid, 5-oxoproline, cadaverine, hypotarine, phenylalanine, aspartic acid, 5-amino-valeric acid, succinic acid, indole-3-acetic acid, glutamic acid, alanine-3TMS, putrescine, leucine, N-acetylornithine, hydrocinnamate, ornithine, fucose-2, fructose-6-phosphate.
	Saliva			High PISA (decreased by debridement): 4-aminobutyric acid, cadaverine, phenylalanine, 5-aminovaleric acid, succinic acid, putrescine, hydrocinnamate, ornithine, fructose-6 phosphate
				Low PISA (predebridement): 5-oxoproline, aspartic acid, tryptophan, glutamine, fucose-2, glutamic acid, indole-3-acetic acid, N-acetylornithine, isoleucine-1TMS, fucose-1, ethanolamine, leucine, alanine-3TMS, hypotaurine, alanine-2TMS
				Low PISA (decreased by debridement): tryptophan, glutamine, isoleucine-1TMS, fucose-1, ethanolamine, alanine-2TMS
Kuboniwa et al (2016)¹⁰¹	Saliva	Periodontitis	GC-MS	Supra-/subgingival: increased ornithine, 5-oxyproline, valine, spermidine, hydrocinnamate, histidine, cadaverine
Kuboniwa et al (2016)¹⁰¹	Saliva	Periodontitis	GC-MS	Sub- vs supragingival (postdebridement): decreased cadverine ornithine, spermidine, 5-oxoproline
Ozeki et al (2016)⁹⁶	Gingival crevicular fluid	Moderate pocket depth	GC-MS	Moderate pocket depth: increased propylamide, lactic acid, benzoic acid, glycine, phosphate, succinic acid, alanine, malic acid, glutamic acid, 5-aminocaleric acid, phenylalanine, inositol, octadecanoate; decreased hydrocinnamate
Ozeki et al (2016)⁹⁶	Gingival crevicular fluid	Deep pocket depth	GC-MS	Deep pocket depth: increased propylamide, lactic acid, benzoic acid, phosphate, glycine, succinic acid, alanine, hydrocinnamate, malic acid, glutamic acid, 5-aminovaleric acid, phenylalanine, ribose, taurine, putrescine, galactose, lysine, inositol, octadecanoate
Barnes et al (2011)⁹⁵	Saliva	Healthy, gingivitis, and periodontitis	LC-MS and GC-MS	Diabetic saliva and plasma: decreased 1–5 anhydroglucitol, increased glucose, increased alpha-hydroxybutyrate
	Plasma			Saliva periodontitis vs healthy: increased purine degradation (oxidative stress), dipeptides (macromolecular degradation of proteins), amino acid metabolites (p-cresol sulfate), carbohydrates (monosaccharides indicative of amylase activity), energy metabolites (TCA, indicative of energenic stress), uridine (DNA/RNA degradation), allanation, omega-6 fatty acids (link to inflammation), fatty acids, acetylcarnitine, carnitine, 3-dehydrocarnitine
				Diabetic gingivitis vs diabetic healthy (saliva): (purine degradation) increased adenosine, inosine, guanine, guanosine, xanthine, glutathione (oxidized), cysteine-glutathione disulfide
				Diabetes and periodontal disease (fatty acids and sphingomyelins): 12-HETE, linoleate (18:2n6), linoleate (alpha or gamma 18n3 or 6), docosapentaenoate (n3 DPA, 22:5n3), arachidonate (20:4n6), palmitoyl sphingoyelin
Huang et al (2014)¹⁰⁰	Saliva	Chronic periodontitis	GC-MS	Redox status: decreased vitamin A, vitamin B1, vitamin B2, vitamin PP, vitamin C, vitamin E, Ca, Mg, Cu, Fe, Se, Zn, K, Ca, Mn
				Fatty acids: decreased C12:0, C14:0
				Aracidonic acid metabolites: increased prostaglandin D2, prostaglandin E2, prostaglandin F2alpha, thromboxane B2, 5-HETE; decreased prostaglandin I2, 9-HODE, 13-HODE

5-HETE, 5-hydroxyeicosatetraenoic acid; 12-HETE, 12-hydroxyeicosatetraenoic acid; 9-HODE, 9-hydroxyoctadecadienoic acid; 13-HODE, 13-hydroxyoctadecadienoic acid; Ca, calcium; Cu, copper; DPA, docosapentaenoic acid; Fe, iron; GC-MS, gas chromatography-mass spectrometry; H-NMR, proton nuclear magnetic resonance; K, potassium; LC-MS, liquid chromatography-mass spectrometry; Mg, magnesium; Mn, manganese; PISA periodontal inflamed surface area; TCA, tricarboxylic acid; Se, selenium; Zn, zinc.