Journal Article Epublish
PubMed: 42450025 DOI: 10.3390/ijms27135753
A Dysbiosis-Urolithin A Depletion-Low 6-Sulfatoxymelatonin Triad as a Composite Biomarker Framework Across Age-Related Vascular and Malignant Disease States.
Int J Mol Sci 27(13)
Authors: Alexandre Tavartkiladze, Levan Tavartkiladze, Gaiane Simonia, Michel Burnier, Russel J Reiter, Ruite Lou, Dinara Kasradze, Nana Okrostsvaridze, Pati Revazishvili, Irine Andronikashvili, Pirdara Nozadze, Rusudan Khutsishvili
Affiliations
- Department of Internal Medicine, Faculty of Medicine, Tbilisi State Medical University, 0186 Tbilisi, Georgia.
- Institute for Personalized Medicine, 0186 Tbilisi, Georgia.
- Department of Biotechnology, Foconsci Chemical Industry, Shaoxing 312000, China.
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland.
- Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Abstract
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.
MeSH
Cytokines, Dysbiosis, Hypertension, Tumor Necrosis Factor-Alpha, Melatonin, Neoplasms, Interleukin-6, Interleukin-8, Oxidative Stress, Biomarkers, Gastrointestinal Microbiome