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Limosilactobacillus mucosae attenuates hyperlipidemic periodontitis via the gut-oral axis

Jing-ling Xu,Ziyi Han,Qing Xue,Haoran Wang,Jiyu Song,Yutong Li,Yongfeng Zhang,Di Wang,Min Hu

Published 2026 in Gut microbes

ABSTRACT

ABSTRACT The link between hyperlipidemia and periodontitis is well-established, but the underlying mechanisms remain incompletely understood. Here, we reveal a critical role for a ‘gut-oral’ axis in mediating this interaction. Integrating multi-omics analyses of clinical samples and mouse models, we identified that a significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis (HPD). Fecal microbiota transplantation established a causal link between this gut dysbiosis and exacerbated periodontitis. Mechanistically, oral administration of live L. mucosae ameliorates HPD by restoring intestinal levels of the key metabolite, glycerophosphocholine (α-GPC). Notably, supplementation with α-GPC alone recapitulated this protective effect by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue. This reinforcement of the epithelial barrier curtailed inflammatory infiltration and restored bone homeostasis. Our findings uncover a protective ‘L. mucosae–α-GPC–CLDN1’ axis, providing mechanistic insight into how gut microbiota mediates metabolism-associated inflammation and proposing a potential therapeutic strategy for HPD.

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