Associations Between Gut Microbiota and Mitochondrial Metabolites, with Growth Differentiation Factor-15 as a Marker of Oxidative Stress in Heart Failure vs. Healthy Ageing

Prokopidis, Konstantinos and Burke, Adam and Altinpinar, Beyza Gulsah and Farahani, Sima Jalali and Khaiyat, Omid and Lip, Gregory YH and Sankaranarayanan, Rajiv and Pekovic-Vaughan, Vanja and Muhamadali, Howbeer and Isanejad, Masoud (2026) Associations Between Gut Microbiota and Mitochondrial Metabolites, with Growth Differentiation Factor-15 as a Marker of Oxidative Stress in Heart Failure vs. Healthy Ageing. Antioxidants, 15 (2). ISSN 2076-3921

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Abstract

Growth differentiation factor-15 (GDF-15) is an established marker of oxidative stress and a general stress-response mitokines. In this study, we aim to investigate the association of GDF-15 with the metabolic signature of gut and mitochondrial activity in HF and ageing population. A total of 25 HF (67.9 ± 10.0 years) and 29 age-matched healthy participants (HPs) (67.8 ± 11.1 years) were recruited and underwent detailed body composition assessment via dual X-ray absorptiometry; total fat mass and appendicular lean soft tissue index (ALSTI/body mass index (BMI)) were calculated. Utilizing semi-targeted Gas Chromatography–Mass Spectrometry on fasting plasma, a panel of gut microbial-derived (e.g., hippuric acid, indole derivatives, and sarcosine) and tricarboxylic acid cycle metabolites was identified. Results showed higher GDF-15 tertiles were associated with greater HF prevalence, fat mass, NT-proBNP, and TNF-α (p < 0.05). Gut-derived metabolites exhibited phenotype-specific patterns; 3-hydroxyindole predicted higher fat mass in HP; hippuric acid was inversely related in HF; and sarcosine correlated with GDF-15 only in HP. In HF, GDF-15 was strongly driven by pyruvic and fumaric acid, indicating disease-specific mitochondrial stress. In conclusion, these observed associations could be evaluated in future mechanistic studies as sensitive biomarkers of systemic oxidative stress markers, informing potential microbiome-targeted therapeutic avenues.

Item Type:	Article
Additional Information and Comments:	© 2026 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Faculty / Department:	Faculty of Human and Digital Sciences > School of Health and Sport Sciences
SWORD Depositor:	RISE Symplectic
Depositing User:	RISE Symplectic
Date Deposited:	09 Feb 2026 14:29
Last Modified:	09 Feb 2026 14:29
URI:	https://hira.hope.ac.uk/id/eprint/4839

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