<h3>Background:</h3> Patients diagnosed with spondyloarthritis (SpA) and dysbiosis or an alteration of the microbiota are linked to an inflammatory state with increased resistance to immunomodulatory treatments. <h3>Objectives:</h3> To describe and compare the composition and diversity of the gut microbiome in a group of patients diagnosed with SpA before initiation and after exposure to biologic disease-modifying therapy (anti-TNF or IL-17 inhibitors). <h3>Methods:</h3> Patients over 18 years old, diagnosed with SpA according to ASAS classificatory criteria, were included. They were categorized based on treatment. The microbiome was evaluated before and after starting biologic therapy, and its behavior was compared with healthy controls (HC), conventional treatment, and inflammatory bowel disease (IBD) patients. A descriptive analysis of quantitative and qualitative clinical variables, including the estimation of measures of central tendency and relative frequencies, was performed. Bioinformatics tools, such as QIIME2, determined beta and alpha diversity. Taxonomic groups were analyzed for differences in mean proportions, with a sensitivity cut-off of 0.1 and a p-value less than 0.05, comparison between groups were calculated with White non-parametric T test. <h3>Results:</h3> Sixty-seven samples were included (31 SpA [8 receiving anti-TNF treatment, 12 receiving anti-IL17 treatment, and 11 receiving conventional treatment], 27 HC, and 9 IBD). In the SpA group, 61.9% were male, with a median age of 39 (IQR 34-47) years, axial involvement 81.0%, and 19.1% were HLA-B27 positive. Significant differences in alpha and beta diversity were identified when comparing diagnostic and treatment groups (Figure 1A and 1B). In the taxonomic analysis of SpA vs. HC, there was an enrichment of <i>Pseudomonadota</i> and <i>Succinivibrio</i> (p=0.008), <i>Muribaculaceae</i> (p=0.016), <i>Bacillaceae</i> (p=0.009), <i>Bacteroides fragilis</i> (p=0.019), as well as <i>Alistipes putredinis</i> (p=0.046). In SpA vs. IBD, there was a decrease in genus <i>Coprobacillus</i> (p=0.021) and <i>Holdemania</i> (p=0.033), as well as <i>A. putredinis</i> (p=0.030). Comparing patients post anti-TNF vs. HC, there was a decrease in the <i>Lachnospiraceae</i> and <i>Clostridiaceae</i> families with a decrease in <i>Clostridium ruminantium</i>, with the restoration of <i>Lactobacillaceae</i> and <i>Odoribacteraceae</i>. Comparing patients post anti-IL17 treatment with HC, there was an enrichment of <i>C. ruminantium</i> and <i>Lachnoclostridium symbiosum</i> with a decrease in the family <i>Bacillaceae</i> and the species <i>A. putredinis</i> (Figure 1C). <h3>Conclusion:</h3> Specific dysbiosis allowed us to distinguish SpA from HC and IBD, with findings similar to those in SpA from countries other than Latin America. After anti-TNF treatment, there was a significant decrease in the <i>Lachnospiraceae</i> family, which may have a regulatory effect (inversely correlated with the activity measured by BASDAI in Ankylosing spondylitis). Furthermore, the families <i>Lactobacillaceae</i> and <i>Odoribacteraceae</i> were restored after anti-TNF treatment (associated with protective effects that decreased colonization of pathogenic bacteria due to intestinal acidification). Patients post anti-IL17 showed a significant decrease in <i>A. putredinis</i>, which has anti-inflammatory functions. Moreover, post anti-IL17 treatment showed an increase in <i>L. symbiosum</i> and <i>C. ruminantium</i> which are related to severe disease activity in ankylosing spondylitis. Meanwhile, post-anti-TNF treatment decreased this last species and was modified in a severe inflammatory response due to infection. Notably, this is the first gut microbiome study performed in Latin America, which included not only patients with reactive arthritis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Ministry of Science, Technology and Innovation, Hospital Militar Central, and Universidad El Bosque. <h3>Disclosure of Interests:</h3> Omar-Javier Calixto Consultant for Janssen, Deisy Abril: None declared, Alejandro Ramos-Casallas: None declared, Javier Escobar: None declared, Eduin Acosta-Hernández: None declared, Juliette De Avila: None declared, Lorena Chila: None declared, Wilson Bautista-Molano Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Juan Manuel Bello-Gualtero: None declared, Consuelo Romero-Sánchez: None declared.