Expansion of intestinal flagellated bacteria is a shared signature across long COVID, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD).
Flagellin activates TLR5 on neutrophils, inducing neutrophil extracellular traps (NETs) and IL-15 release, which in turn promotes macrophage arachidonic acid (ARA) production, fueling systemic inflammation.
Preclinical murine co-infection models replicate multi-organ long COVID phenotypes; targeting macrophage ARA synthesis or neutrophil IL-15 reduces pathology.
Microbiome clearance with gentamicin uniquely attenuates systemic inflammation, positioning intestinal flagellin as a promising therapeutic target and ARA as a biomarker across inflammatory diseases.
