Dextran sulfate sodium-induced colitis exacerbates periodontitis via the NADPH oxidase 2/reactive oxygen species axis in M1-like macrophages

Periodontitis is associated with various systemic diseases, among the most important of which is inflammatory bowel disease (IBD). However, the mechanisms by which IBD exacerbates periodontitis remain unclear. Activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)/reactive oxygen species (ROS) axis in macrophages can worsen intestinal inflammation and periodontitis. Nonetheless, whether IBD aggravates periodontitis by activating the NOX2/ROS axis, specifically in oral macrophages is unknown. In this study, we established animal models and analyzed single-cell RNA data to investigate these pathogenic pathways. Periodontal inflammation was exacerbated via the NOX2/ROS pathway in tumor necrosis factor M1-like macrophages during colitis. Notably, when a NOX2 inhibitor was administered, resulting in reduced ROS expression in periodontal tissue, both periodontal and intestinal inflammation were significantly alleviated, and disruption of the periodontal and intestinal microbiota was reduced. By uncovering the pathogenic pathways linking these two diseases, this study provides insight into potential treatments for periodontitis and related systemic conditions. • Dextran sulfate sodium-induced colitis worsens periodontitis caused by M1-like macrophages. • The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)/reactive oxygen species axis may be a key pathway. • NOX2 inhibitors alleviate oral and gut inflammation and restore microbial homeostasis. • Our findings have therapeutic implications for periodontitis in patients with inflammatory bowel disease.