Decoding Systemic Inflammation in Long COVID and Autoimmune Diseases: The Role of Intestinal Flagellin and the TLR5-IL-15-ARA Axis

MedXY Editorial Team•Aug 22, 2026•Gastroenterology

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.

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This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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.