Microbiome–Metabolome Crosstalk as a Driver of COVID-19 Severity
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Medical Sciences
Authors: Patricia Diez-Echave, María Jesús Rodríguez-Sojo, Benita Martin-Castaño, Laura Hidalgo-García, Antonio Jesús Ruiz-Malagon, José Alberto Molina-Tijeras, Anaïs Redruello Romero, Margarita Martínez-Zaldívar, Emilio Mota, Fernando Cobo, Marta Alvarez-Estevez, Federico García, Concepción Morales-García, Silvia Merlos, Paula García-Flores, Manuel Colmenero-Ruiz, María Nuñez, Andrés Ruiz-Sancho, María Elena Rodríguez-Cabezas, Ángel Carazo Gallego, Emilio Fernandez-Varón, José Pérez del Palacio, Javier Martin, Jorge García-García, Rocío Morón, Alba Rodríguez-Nogales, Julio Gálvez
Institutions: Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Hospital Universitario Virgen de las Nieves, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Instituto de Parasitología y Biomedicina "López - Neyra"
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,689
Funder: Servicio Andaluz de Salud
Award: G2566454597
OpenAlex ID: W7129426562