Table 3.
Two-axis grading of candidate oral and salivary biomarkers: evidence population and stage of biomarker development, by target condition.
| Candidate signature | Target condition | Evidence population | Development phase | Reported diagnostic accuracy | Principal limitation | Reference |
|---|---|---|---|---|---|---|
| Salivary exosomal H. pylori DNA by qPCR, with clarithromycin-resistance genotyping | Gastric H. pylori infection; clarithromycin resistance | Pediatric; n = 500, two centers | Phase 2 | Sensitivity 93.7% (95% CI 88.7-96.9); specificity 80.1% (95% CI 75.5-84.2); PPV 68.5%; NPV 96.5%; confidence intervals calculated by us from the reported counts | No external validation; 68 false positives among 342 uninfected children, so a positive result is not confirmatory and the PPV is 68.5% at the observed prevalence; resistance genotyping agreed with gastric tissue in 103 of 113 (kappa 0.72) | (Song et al., 2026) |
| Salivary H. pylori 23S rRNA gene PCR, with or without cagA | Gastric H. pylori infection | Pediatric; n = 100, single center | Phase 2 | Sensitivity 86.9% (95% CI 75.8-94.2); specificity 100% (95% CI 91.0-100); calculated by us from the reported counts | Single small cohort; reference standard was Giemsa histology alone; cannot distinguish oral residence from reflux-derived contamination; cagA detected in eight samples | (Samani et al., 2026) |
| Oral Porphyromonas enrichment | Oral H. pylori carriage | Pediatric and adult; 21 children | Phase 1 | NR (community comparison only) | Cross-sectional; genus level only; no standardized assay or threshold; link to gastritis unproven | (Ogaya et al., 2024) |
| Tongue-coating Campylobacter concisus | Gastritis and precancerous cascade | Adult only | Phase 1 | NR | No pediatric data; PCR cross-reaction with other Campylobacter species | (Cui et al., 2019; Scholz et al., 2025) |
| Low salivary F. nucleatum and P. gingivalis | H. pylori-negative chronic gastritis | Adult only; exploratory, n = 21 | Phase 1 | NR | Small exploratory cohort; direction opposite to that reported in gastric cancer; no pediatric data | (Contaldo et al., 2021) |
| Gastric-cancer-enriched genera (Fusobacterium, Parvimonas, Veillonella, Prevotella, Peptostreptococcus) | Gastric carcinogenesis, not pediatric gastritis | Adult only | Phase 2 | Eight-taxon mucosal classifier, area under the curve 0.85 (gastric cancer versus superficial gastritis); not reported for any single genus | Reaches Phase 2 for a target condition and population other than those this review addresses; direction is context-dependent; transfer to children untested | (Liu et al., 2022); (Coker et al., 2018; Ferreira et al., 2018) |
| Metabolic signatures (enterosalivary nitrate-nitrite-nitric oxide pathway) | Mechanism; no clinical target condition defined in children | Adult and non-human | Phase 1 | NR | Strongly diet-dependent; no pediatric gastritis-specific evaluation | (Hyde et al., 2014; Yang et al., 2025) |
| Volatile organic compound and breath signatures | Gastric H. pylori infection in adults | Adult only | Phase 1 | NR | Platform-development stage; no pediatric data | (Flores Rangel et al., 2025) |
| Strain-level translocation markers | Oral-to-gut strain transfer, not gastritis | Pediatric; stunting cohort, n = 44 | Phase 1 | NR | Different cohort and target condition; not a deployable assay | (Yersin et al., 2026) |
| Machine-learning classifiers | Gastric cancer or digestive-tract tumours | Adult only; single-center and multicenter | Phase 2 | Area under the curve 0.91 for a multicenter tongue-coating metaproteomic model and for an eight-genus salivary panel | Adult population and cancer endpoint throughout; no classifier developed or validated in children was identified, so transfer to pediatric gastritis is untested | (Huang et al., 2021); (Yuan et al., 2023; Chen et al., 2024; Kim et al., 2026) |
| Host regulatory-response signature (FOXP3, IL-10, TGF-beta) | Clinically meaningful disease activity (proposed; hypothesis H3) | Pediatric | Phase 1 | NR | Hypothesis only; no assay or threshold defined; the only candidate addressing the activity-level endpoint | (Harris et al., 2008; Brawner et al., 2017) |
Candidates are graded on two independent axes, as defined in Section 2. Evidence population: pediatric, at least one study in participants under 18 years reporting the marker for the stated target condition; adult, evidence restricted to adults; non-human, animal, cell-culture, or isolate-level work only. Development phase, after Pepe et al. (2001): Phase 1, exploratory, with no standardized assay; Phase 2, standardized assay applied to clinically obtained specimens with accuracy estimated against a reference standard; Phase 3, retrospective longitudinal; Phase 4, prospective application in the intended-use population with a prespecified threshold; Phase 5, demonstrated effect on clinical decisions or outcomes. Where a primary study reports no accuracy metric the phase is capped at Phase 1. That no candidate reaches Phase 3 or beyond, and that no candidate has been evaluated in children against histological gastritis or disease activity as the target condition, are themselves findings. No machine-learning classifier for an oral or salivary signature that was developed or validated in children was identified. NR, not reported; CI, confidence interval.