Metatranscriptomic analysis reveals gut microbiome bacterial genes in pyruvate and amino acid metabolism associated with hyperuricemia and gout in humans
Several pathologies with metabolic origin, such as hyperuricemia and gout, have been associated with the gut microbiota taxonomic profile. However, there is no evidence of which bacterial genes are being expressed in the gut microbiome, and of their potential effects on hyperuricemia and gout. We sequenced the RNA of 26 fecal samples from 10 healthy normouricemic controls, 10 with asymptomatic hyperuricemia (AH), and six gout patients. The coding sequences were mapped to KEGG orthologues (KO). We compared the expression levels using generalized linear models and validated the expression of four KO in a larger sample by qRT-PCR. A distinct genetic expression pattern was identified among groups. AH individuals and gout patients showed an over-expression of KOs mainly related to pyruvate metabolism (Log2foldchange > 23, p-adj ≤ 3.56 × 10<sup>- 9</sup>), the pentose pathway (Log2foldchange > 24, p-adj < 1.10 × 10<sup>-12</sup>) and purine metabolism (Log2foldchange > 22, p-adj < 1.25 × 10<sup>- 7</sup>). AH subjects had lower expression of KO related to glycine metabolism (Log2foldchange=-18, p-adj < 1.72 × 10<sup>-6</sup>) than controls. Gout patients had lower expression (Log2foldchange=-22.42, p-adj < 3.31 × 10<sup>- 16</sup>) of a KO involved in phenylalanine biosynthesis, in comparison to controls and AH subjects. The over-expression seen for the KO related to pyruvate metabolism and the pentose pathway in gout patients´ microbiome was validated. There is a differential gene expression pattern in the gut microbiome of normouricemic individuals, AH subjects and gout patients. These differences are mainly located in metabolic pathways involved in acetate precursors and bioavailability of amino acids.
Authors
- Carlos Martínez-Armenta (ORCID: https://orcid.org/0000-0003-0413-4930)
- Dafne Lissete Guido-Gómora
- Janitzia Vázquez‐Mellado (ORCID: https://orcid.org/0000-0001-6636-2301)
- Yessica Zamudio‐Cuevas (ORCID: https://orcid.org/0000-0003-1751-3454)
- Alfredo Lagunas-Martínez (ORCID: https://orcid.org/0000-0002-1206-0161)
- Mireya Martínez-García (ORCID: https://orcid.org/0000-0002-2876-8500)
- Alberto López-Reyes (ORCID: https://orcid.org/0000-0002-2575-2589)
- María del Carmen Camacho-Rea (ORCID: https://orcid.org/0000-0002-1858-8071)
- Carlos Suárez-Ahedo (ORCID: https://orcid.org/0000-0001-9766-2411)
- Ana I. Burguete-García (ORCID: https://orcid.org/0000-0003-4645-2494)
- Carlos Alberto Lozada-Pérez (ORCID: https://orcid.org/0000-0001-8809-6526)
- Javier Fernández‐Torres (ORCID: https://orcid.org/0000-0002-7271-2862)
- Laura E. Martínez-Gómez (ORCID: https://orcid.org/0000-0003-3198-1350)
- Karina Martínez‐Flores (ORCID: https://orcid.org/0000-0003-0675-0227)
- Eder Orlando Méndez-Salazar (ORCID: https://orcid.org/0000-0001-5167-5567)
- Berenice Palacios‐González (ORCID: https://orcid.org/0000-0002-7848-1532)
- Brígida Herrera-López
- Luis Manuel Amezcua-Guerra (ORCID: https://orcid.org/0000-0002-6258-5732)
- Guadalupe Obdulia Gutiérrez-Esparza (ORCID: https://orcid.org/0000-0003-0090-2701)
- Joaquı́n Dopazo (ORCID: https://orcid.org/0000-0003-3318-120X)
- Yaneth Citlalli Orbe-Orihuela
- Adriana Francisco-Balderas (ORCID: https://orcid.org/0000-0001-8414-3436)
- Carlos S. Casimiro‐Soriguer (ORCID: https://orcid.org/0000-0003-1774-2580)
- Gabriela Angélica Martínez‐Nava (ORCID: https://orcid.org/0000-0001-9857-3840)
- Efren Altamirano-Molina
- Sarahí Valle-Gutiérrez
- Carlos Pineda (ORCID: https://orcid.org/0000-0003-0544-7461)
Institutions
- Universidad Autónoma Metropolitana (MX)
- Hospital General de México (MX)
- Fundación Progreso y Salud (ES)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- Hospital Médica Sur (MX)
- National Institute of Genomic Medicine (MX)
- Hospital General De Zona (MX)
- Instituto Nacional de Rehabilitación (MX)
- Instituto Nacional de Salud Pública (MX)
- Instituto de Biomedicina de Sevilla (ES)
- Instituto Nacional de Cardiología (MX)
- Instituto Politécnico Nacional (MX)
- Université de Montréal (CA)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-03-22
- DOI
- https://doi.org/10.1038/s41598-025-93899-1
- Citations
- 6
- Primary Topic
- Gout, Hyperuricemia, Uric Acid
- Type
- article
- Field-Weighted Citation Impact
- 8.58
Funders
- Consejo Nacional de Ciencia y Tecnología