{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T10:35:09Z","timestamp":1771324509373,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018780","name":"Government of Andalucia","doi-asserted-by":"publisher","award":["CV20-99908"],"award-info":[{"award-number":["CV20-99908"]}],"id":[{"id":"10.13039\/501100018780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: COVID-19, caused by SARS-CoV-2, exhibits highly variable severity, from mild symptoms to respiratory failure and multiorgan dysfunction. Traditional risk factors incompletely explain this heterogeneity, highlighting the potential role of gut microbiota and host metabolomics in modulating immune responses. Methods: Thus, this study investigates how gut microbiota variations are associated with plasma metabolite profiles in COVID-19, exploring relationships between microbial and metabolic signatures and disease severity and potential therapeutic targets. In a prospective cohort of 55 patients, stool and plasma samples were analyzed using 16S rRNA sequencing and untargeted LC-HRMS metabolomics. Results: Severe COVID-19 was associated with reduced microbial diversity and enrichment of pro-inflammatory taxa, including Prevotella, Alistipes, Dialister, and Lachnoclostridium, whereas mild cases showed higher abundance of protective commensals such as Bacteroides, Faecalibacterium, and Blautia. Metabolomic profiling revealed alterations in bile acids, unsaturated fatty acids, tryptophan, and inositol phosphate pathways. Notably, linoleate levels were elevated in severe cases, showing correlations with pro-inflammatory microbes, while acylcarnitines and inositol derivatives were enriched in mild disease. Predictive functional analysis suggested that severe-associated microbes showed enhanced amino acid catabolism, oxidative glucose metabolism, and xenobiotic degradation, which may be linked to host inflammation. Conclusions: These findings highlight associations between gut microbiota composition, microbial metabolism, and circulating metabolites in COVID-19 severity. Identified microbial and metabolomic signatures may represent potential candidates to be considered biomarkers and therapeutic targets to modulate disease progression.<\/jats:p>","DOI":"10.3390\/medsci14010097","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T09:22:46Z","timestamp":1771320166000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome\u2013Metabolome Crosstalk as a Driver of COVID-19 Severity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4493-3091","authenticated-orcid":false,"given":"Patricia","family":"Diez-Echave","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1693-505X","authenticated-orcid":false,"given":"Mar\u00eda Jes\u00fas","family":"Rodr\u00edguez-Sojo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benita","family":"Martin-Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Centro de Salud Las Gabias, Distrito Granada-Metropolitano, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Hidalgo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-650X","authenticated-orcid":false,"given":"Antonio Jes\u00fas","family":"Ruiz-Malagon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-9226","authenticated-orcid":false,"given":"Jos\u00e9 Alberto","family":"Molina-Tijeras","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00efs Redruello","family":"Romero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Mart\u00ednez-Zald\u00edvar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"},{"name":"Centro de Salud \u201cSalvador Caballero\u201d, Distrito Granada-Metropolitano, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-9947","authenticated-orcid":false,"given":"Emilio","family":"Mota","sequence":"additional","affiliation":[{"name":"Centro de Salud \u201cSalvador Caballero\u201d, Distrito Granada-Metropolitano, 18012 Granada, 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Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"ref_1","unstructured":"(2025, November 19). 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