Gut commensal Odoribacter splanchnicus attenuates hyperlipidemic periodontitis via gut-oral metabolic transmission of β-GPA.

Abstract

Hyperlipidemic periodontitis (HPD) represents a prevalent comorbidity linking systemic metabolic dysregulation with local inflammation, yet the microbial mechanisms driving this gut-oral crosstalk remain elusive. Here, the comorbid state of HPD is linked to hyperlipidemia-associated gut microbiota changes, which are prominently accompanied by the depletion of Odoribacter splanchnicus in both patients and mice. Fecal microbiota transplantation demonstrates that this gut dysbiosis exacerbates periodontal destruction when local inflammation is present. Mechanistically, intragastric administration of live O. splanchnicus ameliorates HPD by remodeling the gut ecosystem and upregulating the metabolite β-guanidinopropionic acid (β-GPA). Notably, direct supplementation with β-GPA reproduces these protective effects. Furthermore, β-GPA is proposed as a systemic effector linking the gut and periodontal tissues, where its protective effect is associated with the suppression of the pro-inflammatory Toll-like receptor 4 (TLR4) signaling cascade. These findings highlight a link involving O. splanchnicus, β-GPA, and the modulation of TLR4 signaling, offering a potential microbiome-based therapeutic strategy for managing complex metabolic-inflammatory comorbidities.