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

Tavartkiladze, Alexandre; Tavartkiladze, Levan; Simonia, Gaiane; Burnier, Michel; Reiter, Russel J.; Lou, Ruite; Kasradze, Dinara; Okrostsvaridze, Nana; Revazishvili, Pati; Andronikashvili, Irine; Nozadze, Pirdara; Khutsishvili, Rusudan

doi:10.3390/ijms27135753

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

by

Alexandre Tavartkiladze

^1,2,3,*

,

Levan Tavartkiladze

²,

Gaiane Simonia

^1,2,

Michel Burnier

⁴

,

Russel J. Reiter

⁵

,

Ruite Lou

³,

Dinara Kasradze

²,

Nana Okrostsvaridze

²,

Pati Revazishvili

^1,2,

Irine Andronikashvili

^1,2,

Pirdara Nozadze

^1,2 and

Rusudan Khutsishvili

²

¹

Department of Internal Medicine, Faculty of Medicine, Tbilisi State Medical University, 0186 Tbilisi, Georgia

²

Institute for Personalized Medicine, 0186 Tbilisi, Georgia

³

Department of Biotechnology, Foconsci Chemical Industry, Shaoxing 312000, China

⁴

Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland

⁵

Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(13), 5753; https://doi.org/10.3390/ijms27135753 (registering DOI)

Submission received: 21 May 2026 / Revised: 4 June 2026 / Accepted: 25 June 2026 / Published: 25 June 2026

(This article belongs to the Special Issue Microbiome Connections in Age-Related Diseases)

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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.

Keywords: urolithin A; gut microbiota; dysbiosis; salt-sensitive hypertension; melatonin; 6-sulfatoxymelatonin; cytokines; oxidative stress; inflammaging; advanced cancer; composite biomarker triad

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MDPI and ACS Style

Tavartkiladze, A.; Tavartkiladze, L.; Simonia, G.; Burnier, M.; Reiter, R.J.; Lou, R.; Kasradze, D.; Okrostsvaridze, N.; Revazishvili, P.; Andronikashvili, I.; et al. 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. 2026, 27, 5753. https://doi.org/10.3390/ijms27135753

AMA Style

Tavartkiladze A, Tavartkiladze L, Simonia G, Burnier M, Reiter RJ, Lou R, Kasradze D, Okrostsvaridze N, Revazishvili P, Andronikashvili I, et al. A Dysbiosis–Urolithin A Depletion–Low 6-Sulfatoxymelatonin Triad as a Composite Biomarker Framework Across Age-Related Vascular and Malignant Disease States. International Journal of Molecular Sciences. 2026; 27(13):5753. https://doi.org/10.3390/ijms27135753

Chicago/Turabian Style

Tavartkiladze, Alexandre, Levan Tavartkiladze, Gaiane Simonia, Michel Burnier, Russel J. Reiter, Ruite Lou, Dinara Kasradze, Nana Okrostsvaridze, Pati Revazishvili, Irine Andronikashvili, and et al. 2026. "A Dysbiosis–Urolithin A Depletion–Low 6-Sulfatoxymelatonin Triad as a Composite Biomarker Framework Across Age-Related Vascular and Malignant Disease States" International Journal of Molecular Sciences 27, no. 13: 5753. https://doi.org/10.3390/ijms27135753

APA Style

Tavartkiladze, A., Tavartkiladze, L., Simonia, G., Burnier, M., Reiter, R. J., Lou, R., Kasradze, D., Okrostsvaridze, N., Revazishvili, P., Andronikashvili, I., Nozadze, P., & Khutsishvili, R. (2026). A Dysbiosis–Urolithin A Depletion–Low 6-Sulfatoxymelatonin Triad as a Composite Biomarker Framework Across Age-Related Vascular and Malignant Disease States. International Journal of Molecular Sciences, 27(13), 5753. https://doi.org/10.3390/ijms27135753

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

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