Salivary pathobiont Klebsiella pneumoniae exacerbating periodontitis-related intestinal dyshomeostasis and accelerated metabolic syndrome.

OBJECTIVE The relationship between periodontitis and diabetes is well-established, yet the underlying mechanisms are incompletely understood. This study aimed to investigate the role of Klebsiella pneumoniae (Kp94), isolated from the salivary microbiota of periodontitis patients, in exacerbating diabetes by disrupting intestinal immunity and metabolic homeostasis.

DESIGN Following the induction of periodontitis by ligation and oral gavage of Kp94, the systemic metabolic status of the mice was assessed through the Disease Activity Index (DAI), intraperitoneal glucose tolerance test (IPGTT), and measurements of serum total cholesterol (TC) and glycated hemoglobin (HbA1c). To investigate the underlying mechanisms, transcriptomic analysis of intestinal tissues and 16S rRNA sequencing of intestinal contents were performed. Furthermore, intestinal immunity was evaluated by immunohistochemistry/immunofluorescence, and the proportion of ILC3s was analyzed by flow cytometry.

RESULTS Kp94 induced gut microbiota dysbiosis and systemic glucose intolerance. Mechanistically, Kp94 suppressed the intestinal ILC3/IL-22 pathway, which impaired mucosal immunity by reducing antimicrobial peptide (BD3, LCN2) expression, disrupting the mucus barrier, and increasing intestinal permeability. Concomitantly, this suppression inhibited endocrine function, notably GLP-1 production. Crucially, IL-22 administration rescued these defects by alleviating endoplasmic reticulum stress, thereby restoring barrier and endocrine integrity, and improving metabolic parameters, including HbA1c.

CONCLUSION Our findings suggest that the intestinal ILC3/IL-22 pathway may serve as a potential mechanistic link and therapeutic target for the metabolic and pancreatic damage associated with Kp94 in periodontitis-related diabetes.