Influence of TNF-α Inhibitors on Gut Microbiota and Immune Modulation in Treating Ankylosing Spondylitis: Insights into Therapeutic Mechanisms and Clinical Implications

Yue-Xing Yuan,1,* Shou-Rui Feng,2,* Ai-Yu Wu,1 Wei-Hao Wu,1 Pan Tian,1 Ai-Zhen Chen,1 Xiao-Mei Ma,1 Ling-Ling Huang,1 Lian Yu1 1Department of Hematology and Rheumatology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, People’s Republic of China; 2State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian Yu, Department of Hematology and Rheumatology, Longyan First Hospital Affiliated to Fujian Medical University, No. 105, Jiu Yi North Road, Xin Luo District, Longyan, 364000, People’s Republic of China, Tel +86 13859572936, Fax +86 05972294813, Email [email protected]: This study aims to evaluate the impact of tumor necrosis factor (TNF) inhibitors on the gut microbiota in patients with ankylosing spondylitis (AS) and investigate the potential therapeutic benefits of microbial modulation. Given the role of gut microbiota in immune regulation and its association with autoimmune conditions like AS, this research seeks to identify microbial targets that could enhance treatment outcomes.Methods: Patients with AS undergoing TNF inhibitor therapy and healthy controls were recruited for this study. Gut microbiota samples were collected and analyzed using 16S rRNA gene sequencing. Assessed key parameters included α-diversity and the relative abundance of dominant phyla, such as Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, and Fusobacteriota.Results: Tumor necrosis factor (TNF) inhibitor therapy was found to enhance the α-diversity of the gut microbiota in patients with AS. The dominant phyla identified included Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, and Fusobacteriota. Comparative analysis showed that patients with AS had elevated levels of Proteobacteria and Pasteurellaceae, which were normalized following TNF inhibitor treatment. Functional predictive analysis suggested that pathways associated with Terpenoid backbone biosynthesis and photosynthesis were reduced in patients with AS, bringing them closer to the profiles observed in healthy controls.Conclusion: TNF inhibitors may contribute to the treatment of AS by promoting beneficial microbes, reducing the prevalence of disease-associated microbes, and modulating microbial functions. These findings bring valuable insights into the mechanisms of how TNF inhibitors act and highlight potential microbial targets for therapeutic interventions in AS.Keywords: ankylosing spondylitis, gut microbiota, inflammation, immune system dysregulation, microbial diversity, TNF inhibitors