Dissertação de Mestrado Nutrição Humana e Metabolismo 2023 Faculdade de Ciências Médicas, Universidade NOVA de Lisboa

Background: The etiopathogenesis of axial spondyloarthritis (axSpA) is not completely understood and growing evidence suggests that gut microbiota could play an important role in the initiation and progression of axSpA. The introduction of anti-Tumor Necrosis Factor (anti-TNF) therapy has revolutionized the treatment of axSpA in patients, however a significant proportion of patients do not respond to these costly drugs. Thus, it is urgent and necessary to understand the factors that impact the response to therapy and identify new predictors of therapeutic efficacy. Aim: To evaluate the relationship between fecal microbiota composition and anti-TNF therapy in Portuguese axSpA patients with high levels of disease activity. In addition, fecal microbiota composition was characterized and associations between bacterial taxa and disease activity were explored. Methodology: This pilot is a 14-week prospective observational study that included axSpA patients with indication for anti-TNF therapy referenced from HEM. A total of two fecal samples from each patient was collected at baseline and after 14 weeks on anti-TNF treatment. Bacterial DNA present was extracted from samples and specific bacterial groups were identified and quantified by 16S rDNA sequencing. axSpA activity was assessed at each time point using Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Results: We observed that adalimumab (anti-TNF drug) impacts fecal microbiota composition shifting the abundance of specific genera by increasing abundance of Bifidobacterium, Butyrivibrio, Pseudobutyrivibrio, Eubacterium and Sutterella and decreasing abundance of Porphyromonas. Porphyromonas was identified as a biomarker of disease activity. Our findings reinforced previous observations that patients with higher inflammatory status and higher disease activity are more likely to respond to anti-TNF treatment. Our investigation suggested that the fecal microbiota may be a potential tool for predicting the treatment response to adalimumab in axSpA patients, as fecal microbiota characterized by higher abundance of Anaerovorax, Coprococcus, Lautropia, Rothia, Saccharothrix, Succiniclasticum and Veillonella was associated with failure to respond to treatment and SpA patients may respond to anti-TNF treatment more effectively if they exhibit increased bacterial richness and increased abundances of Gemmatimonadetes, Atopobium, Burkholderia and Escheria. Conclusion: This pilot study revealed interesting preliminary data on fecal microbiota features in Portuguese axSpA patients, provided insights into the dynamic microbiota alterations after 14 weeks of adalimumab treatment and identified microbial biomarkers of treatment response that could pave the way to development of precision therapy in axSpA.