Limosilactobacillus mucosae attenuates hyperlipidemic periodontitis via the gut-oral axis.

Significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis identified through multi-omics analyses of clinical samples and mouse models.

• The finding was derived from integrating multi-omics analyses of both clinical samples and mouse models.
• L. mucosae was identified as a depleted gut commensal specifically associated with the hyperlipidemic periodontitis condition.
• This reduction was characterized as a 'key feature' of hyperlipidemic periodontitis (HPD).

Fecal microbiota transplantation established a causal link between gut dysbiosis and exacerbated periodontitis in hyperlipidemia.

• FMT was used as the experimental approach to demonstrate causality between gut microbiome alterations and periodontitis severity.
• The gut dysbiosis associated with hyperlipidemia was shown to causally worsen periodontitis, not merely correlate with it.
• This finding elevated the relationship from associative to mechanistic/causal.

Oral administration of live L. mucosae ameliorates hyperlipidemic periodontitis by restoring intestinal levels of the key metabolite glycerophosphocholine (α-GPC).

• The route of administration was oral, and live bacteria were required for the protective effect.
• α-GPC (glycerophosphocholine) was identified as the key metabolite mediating the protective effect.
• L. mucosae's protective mechanism operates through restoration of intestinal α-GPC levels rather than direct action on periodontal tissue.

Supplementation with α-GPC alone recapitulated the protective effect of L. mucosae against hyperlipidemic periodontitis.

• α-GPC supplementation alone was sufficient to reproduce the protective effects observed with L. mucosae administration.
• The protective effect of α-GPC was mediated by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue.
• This finding demonstrated that α-GPC is a sufficient downstream effector of L. mucosae's protective action.

Upregulation of Claudin-1 (CLDN1) in periodontal tissue by α-GPC reinforces the epithelial barrier, curtailing inflammatory infiltration and restoring bone homeostasis.

• CLDN1 is a tight junction protein whose upregulation in periodontal tissue was identified as the downstream mechanism of α-GPC supplementation.
• Reinforcement of the epithelial barrier led to curtailed inflammatory infiltration in periodontal tissue.
• Restoration of bone homeostasis was also observed as an outcome of this barrier reinforcement.
• This mechanism links gut metabolite changes to structural and inflammatory outcomes in the periodontium.

The study reveals a protective 'L. mucosae–α-GPC–CLDN1' axis that provides mechanistic insight into how gut microbiota mediates metabolism-associated inflammation in hyperlipidemic periodontitis.

• The axis connects a gut commensal bacterium (L. mucosae), an intestinal metabolite (α-GPC), and a periodontal tight junction protein (CLDN1) in a sequential protective pathway.
• The findings propose this axis as a potential therapeutic strategy for HPD.
• The mechanism illustrates how gut microbiota can mediate metabolism-associated inflammation at a distant oral site via a gut-oral axis.