AB0102 DIFFERENTIAL EXPRESSION OF ORTHOLOGUE GENES INVOLVED IN GLYCINE AND PYRUVATE METABOLISM CHARACTERIZE THE GUT MICROBIOME META-TRANSCRIPTOME OF SUBJECTS WITH ASYMPTOMATIC HYPERURICEMIA AND GOUT
Authors: G. A. Martínez-Nava, E. Altamirano-Molina, J. Vazquez Mellado, C. Casimiro-Soriguer, J. Dopazo, C. A. Lozada Perez, D. L. Guido-Gomora, S. Valle-Gutierrez, B. Herrera-López, L. E. Martinez-Gomez, C. Martinez-Armenta, C. Suarez-Ahedo, Y. Zamudio Cuevas, K. Martinez Flores, J. Férnandez-Torres, A. Francisco-Balderas, A. I. Burguete-Garcia, C. Orbe-Orhihuela, A. Lagunas-Martínez, E. O. Mendez-Salazar, B. Palacios-Gonzalez, C. Pineda, A. López-Reyes
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The importance of the gut microbiota in several rheumatic and metabolic pathologies, including hyperuricemia and gout, has been demonstrated by a large body of scientific evidence. However, there are no studies on the specific bacterial genes expressed in the gut microbiome that might have a functional role in hyperuricemia and gout. <h3>Objectives:</h3> The objective of this study was to analyze the meta-transcriptome of the gut microbiome in hyperuricemia and gout patients and normouricemic controls. <h3>Methods:</h3> The meta-transcriptome of 26 stool samples from 10 normouricemic healthy subjects, 10 asymptomatic hyperuricemic (AH) individuals, and 6 gout patients was sequenced using second generation high throughput sequencing. The coding sequences were mapped to gene ontologies (GO) and KEGG orthologues (KO) with the HUMANn3 software. We compared the expression levels through generalized linear models with the DESeq2 R package. The Benjamini-Hochberg approach was used to estimate the false discovery rates in order to adjust for multiple comparisons. <h3>Results:</h3> We identified a distinctive GO and KO expression pattern among gout patients and normouricemic individuals. AH subjects, as well as gout patients, had an over-expression of orthologues related to the metabolism of pyruvate (Log2foldchange &gt;23, p-adj≤3.56x10<sup>-9</sup>), purines (Log2foldchange&gt;22, p-adj&lt;2.90x10-10); and the pentose pathway (Log2foldchange &gt;18, p-adj≤1.68x10<sup>-7</sup>). AH individuals, unlike gout patients, had a lower expression of a KO related to glycine metabolism (Log2foldchange &lt;-18, p-adj≤1.71x10<sup>-6</sup>) in comparison to controls. Gout patients had lower expression of an orthologue involved in phenylalanine biosynthesis compared to normouricemic subjects (Log2foldchange=-22.42, p-adj&lt;3.31x10<sup>-16</sup>) and even than subjects with HA. <h3>Conclusion:</h3> There is a differential gene expression pattern in the gut microbiome of normouricemic, AH individuals, and gout patients. These differences are focused in metabolic pathways involved in the bioavailability of glycine, phenylalanine, and pyruvate, an important acetate precursor in mixed acid and butyric fermentations. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Consejo Nacional de Humanidades, Ciencias y Tecnologías (FORDECYT-PRONACES/87754/2020) and the Unidad de secuenciación (USec) from the Instituto Nacional de Medicina Genómica. <h3>Disclosure of Interests:</h3> <b>None declared.</b>