A Dysbiosis–Urolithin A Depletion–Low 6-Sulfatoxymelatonin Triad as a Composite Biomarker Framework Across Age-Related Vascular and Malignant Disease States

Urolithin A (UA) is a gut microbiota-derived postbiotic generated from dietary ellagitannins, while urinary 6-sulfatoxymelatonin (6-SMT) is a surrogate marker of nocturnal melatonin output. We explored whether dysbiosis, UA depletion, and low 6-SMT define an ordered biomarker pattern across healthy aging, salt-sensitive hypertension, and advanced cancer. In this pilot observational study, patients with advanced solid tumors were classified as Cancer Group 1 (higher aggressiveness; n = 231) or Cancer Group 2 (lower aggressiveness; n = 118) and compared with healthy older controls (n = 117) and elderly participants with salt-sensitive hypertension (n = 333). Plasma UA decreased stepwise from controls (2.24 [1.38–3.12] nmol/L) to salt-sensitive hypertension (1.20 [0.76–1.89] nmol/L), Cancer Group 2 (0.60 [0.32–0.91] nmol/L), and Cancer Group 1, in which most samples were at or below the assay limit (overall p < 0.0001; trend p < 0.0001). Twenty-four-hour urinary 6-SMT declined in parallel, whereas the dysbiosis score, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and malondialdehyde (MDA) increased, and antioxidant indices decreased across the ordered groups (all p < 0.0001). These cross-sectional findings support a hypothesis-generating biomarker framework linking dysbiosis, postbiotic depletion, circadian disruption, inflammation, and redox imbalance across age-related disease states.