Periodontal pathogen Tannerella forsythia promotes liver fibrosis via ICAM-1⁺ neutrophil–dependent hepatic stellate cell activation

Periodontitis is a key driver in the development and progression of liver fibrosis. Nevertheless, how specific periodontal pathogens contribute to liver fibrosis remains elusive. Here, we identify Tannerella forsythia as the crucial mediator in the link between periodontitis and liver fibrosis, which can translocate to the gut and aggravate liver fibrosis. Mechanistically, Tannerella forsythia promotes the infiltration of ICAM-1+ neutrophils and inflammatory response in the liver via disrupting intestinal barrier integrity. ICAM-1+ neutrophils secrete TNF-α, which activates the PI3K/AKT/mTOR pathway in hepatic stellate cells, triggering collagen deposition and fibrogenesis. Conditional knockout of ICAM-1 in neutrophils or global deletion of TNF-α significantly attenuates inflammatory response and liver fibrosis caused by Tannerella forsythia. Taken together, this study identifies an oral-gut-liver axis driven by Tannerella forsythia and provides a prospective therapeutic target for periodontitis-related liver fibrosis. Peridontitis has been linked in the development and progression of liver fibrosis. Here the authors suggest that Tannerella forsythia is linked to the promotion of liver fibrosis by ICAM-1+ neutrophils activating hepatic stellate cells.