Blood biomarkers of Helicobacter pylori-infected chronic gastritis in active versus stable phases: A clinical indicator analysis combined with proteomic and metabolomic investigations

BEIJING, China – July 20, 2026 – A team of researchers from Guang’anmen Hospital, China Academy of Chinese Medical Sciences has developed a minimally invasive blood-based biomarker signature to accurately distinguish active and stable phases of Helicobacter pylori-infected chronic gastritis, addressing a long-standing clinical limitation of invasive endoscopic staging. The findings were published in the open-access journal iMetaMed.

H. pylori infection affects nearly half the global population and causes approximately 90% of all chronic gastritis cases. Patients with this condition often alternate between symptomatic active inflammation and asymptomatic stable phases. Without clear objective blood markers, clinicians currently rely on gastroscopy and histopathology — invasive procedures unsuitable for large-scale screening or frequent follow-up. Unrecognized active inflammation in stable-looking patients raises cumulative risks of gastric erosion, bleeding, atrophy, intestinal metaplasia and even gastric cancer.

To fill this diagnostic gap, the research team first analyzed clinical biochemical data from 1,409 H. pylori gastritis patients aged 15–87 years. Unsupervised K-means clustering identified six routine blood indicators with extremely significant differences (p<0.001) between active and stable groups: hemoglobin (HGB), uric acid (UA), creatine kinase (CK), red cell distribution width-coefficient of variation (RDW-CV), cholinesterase (CHE), and gamma-glutamyl transferase (GGT).

For deeper molecular mechanism exploration, the team recruited 60 gastritis patients (30 active-stage, 30 stable-stage) and 20 healthy volunteers for serum proteomics and untargeted metabolomics profiling. Multi-dimensional analyses including PLS-DA, volcano plots, protein-protein interaction (PPI) networks and KEGG pathway enrichment revealed three interconnected pathological pathways that drive gastritis activity: hematological dysfunction, energy metabolism reprogramming, and actin cytoskeleton reorganization linked to immune cell migration.

In active gastritis, mucosal microbleeding and impaired iron absorption suppress transferrin receptor (TFRC) expression, lowering hemoglobin while elevating RDW-CV to trigger anemia. Inflammatory hypoxia rewires cellular energy supply away from aerobic oxidation toward anaerobic glycolysis, upregulating glycolytic enzyme ENO3 and energy metabolite acetic acid. Meanwhile, altered cytoskeletal proteins including CAPZB, ACTR3 and CFL1 accelerate immune cell infiltration and worsen mucosal tissue damage, forming a self-amplifying inflammatory cycle.

After systematic ROC curve evaluation of single and combined omics markers, the researchers constructed a streamlined triple-biomarker diagnostic panel: HGB (clinical hematology marker), CAPZB (differential serum protein), and acetic acid (key serum metabolite). The combined signature achieved an outstanding AUC of 0.9978 for discriminating active versus stable H. pylori gastritis, outperforming single-index or single-omics models.

This three-marker panel captures disease features across all three core pathological mechanisms, enabling non-invasive, repeatable dynamic monitoring of gastritis activity without repeated gastroscopic biopsies. While the study was conducted within a single-center cohort and requires further validation in larger independent patient groups, the multi-omics integrated framework provides robust preliminary evidence for blood-based precision staging of H. pylori-related gastritis.

The research establishes a translational foundation for convenient, objective blood testing tools to stratify gastritis activity, optimize individualized treatment plans, and support long-term risk surveillance for gastric precancerous lesions. Moving forward, the team will conduct multi-center validation trials to verify the generalizability of the HGB–CAPZB–acetic acid panel and explore its potential application in population-wide digestive disease screening.