The aim of this study was to evaluate the effect of the administration of pasteurized Akkermansia muciniphila and Amuc_1100 on periodontal destruction in lean and obese mice and to determine the impact of the mode of administration.Porphyromonas gingivalis-associated experimental periodontitis was induced in lean and obese mice. After 3 weeks, live, pasteurized A. muciniphila or Amuc_1100 was administered by oral or gastric gavage for three additional weeks. Moreover, an evaluation of the interaction between A. muciniphila and P. gingivalis was performed by RNA-sequencing, and cytokines secretion was measured in exposed macrophages.Oral administration of live, pasteurized A. muciniphila or Amuc_1100 significantly decreased P. gingivalis-induced periodontal destruction and inflammatory infiltrate in lean and obese mice and contributed to the reduction of the plasma level of TNF-α and to the increase of IL-10. The co-culture of A. muciniphila and P. gingivalis induced an increased expression of genes linked to the synthesis of monobactam-related antibiotics in A. muciniphila, while a decrease of the gingipains and type IX secretion system was observed in P. gingivalis. In P. gingivalis-infected macrophages, pasteurized A. muciniphila decreased TNF-α and increased IL-10 levels.Pasteurized A. muciniphila can counteract P. gingivalis-associated periodontal destruction.