{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T22:25:48Z","timestamp":1770243948660,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000377","name":"Vivensa Foundation","doi-asserted-by":"crossref","award":["PDM2006\\7"],"award-info":[{"award-number":["PDM2006\\7"]}],"id":[{"id":"10.13039\/501100000377","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Liverpool Shared Research Facilities"},{"name":"John Glover memorial award","award":["201591765"],"award-info":[{"award-number":["201591765"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 \u00b1 10.0 years) and 29 age-matched healthy participants (HPs) (67.8 \u00b1 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\u2013Mass 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-\u03b1 (p &lt; 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.<\/jats:p>","DOI":"10.3390\/antiox15020199","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:00:58Z","timestamp":1770109258000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Gut Microbiota and Mitochondrial Metabolites, with Growth Differentiation Factor-15 as a Marker of Oxidative Stress in Heart Failure vs. Healthy Ageing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-9388","authenticated-orcid":false,"given":"Konstantinos","family":"Prokopidis","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal Ageing and Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Burke","sequence":"additional","affiliation":[{"name":"Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beyza Gulsah","family":"Altinpinar","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Science, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2987-6336","authenticated-orcid":false,"given":"Sima Jalali","family":"Farahani","sequence":"additional","affiliation":[{"name":"School of Health and Sport Sciences, Liverpool Hope University, Liverpool L16 9JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0509-9172","authenticated-orcid":false,"given":"Omid","family":"Khaiyat","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Science, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2355-2011","authenticated-orcid":false,"given":"Rajiv","family":"Sankaranarayanan","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Ageing and Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Liverpool University Hospital Foundation Trust Liverpool, Liverpool L7 8YE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanja","family":"Pekovic-Vaughan","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Ageing and Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howbeer","family":"Muhamadali","sequence":"additional","affiliation":[{"name":"Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-5152","authenticated-orcid":false,"given":"Masoud","family":"Isanejad","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Ageing and Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/cvr\/cvaf023","article-title":"Opportunities and challenges for the use of human samples in translational cardiovascular research: A scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC","volume":"121","author":"Davidson","year":"2025","journal-title":"Cardiovasc. 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