Akkermansia muciniphila and Its Pili-Like Protein Amuc_1100 Modulate Macrophage Polarization in Experimental Periodontitis

Abstract

Periodontitis is a chronic inflammatory disease triggered by dysbiosis of the oral microbiome. Porphyromonas gingivalis is strongly implicated in periodontal inflammation, gingival tissue destruction and alveolar bone loss through sustained exacerbation of the host response. Recently, the use of other bacterial species, such as Akkermansia muciniphila, has been suggested to counteract P. gingivalis elicited inflammation. In this study, the effect of A. muciniphila and its pili-like protein Amuc_1100 was evaluated on macrophage polarization during P. gingivalis infection in a murine model of experimental periodontitis. Mice were gavaged with P. gingivalis alone, or in combination with A. muciniphila or Amuc_1100 during 6 weeks. Morphometric analysis demonstrated that the addition of A. muciniphila or Amuc_1100 significantly reduced P. gingivalis induced alveolar bone loss. This decreased bone loss was associated with a pro-resolutive phenotype (M2) of macrophages isolated from submandibular lymph nodes as observed by flow cytometry. Furthermore, the expression of IL-10 at the RNA and protein level was significantly increased in the gingival tissue of the mice and of macrophages exposed to A. muciniphila or Amuc_1100, confirming their anti-inflammatory properties. This study demonstrates the putative therapeutic interest of the administration of A. muciniphila or Amuc_1100 in the management of periodontitis through their anti-inflammatory properties.

Authors' Response: “Akkermansia muciniphila reduces Porphyromonas gingivalis induced inflammation and periodontal bone destruction”

“…In vitro, we observed that IL-10 was increased only when bone marrow macrophages were exposed to A. muciniphila. These results were corroborated in a more recent study (Mulhall et al, 2021), where in vivo administration of A. muciniphila and the pili-like protein Amuc_1100 resulted in an increased population of M2 macrophages as well as increased gene and protein expression of IL-10 within the gingival tissue (Mulhall et al, 2021). As noted by Janket et al, IL-10 produced by macrophages can contribute to the restoration of the epithelial barrier observed in vivo.…”

Pasteurized Akkermansia muciniphila reduces periodontal and systemic inflammation induced by Porphyromonas gingivalis in lean and obese mice

“…Previously, we had demonstrated that oral administration of viable A. muciniphila or pili‐like protein Amuc_1100 during experimental periodontitis resulted in decreased alveolar bone loss, increased IL‐10 production, and decreased pro‐inflammatory IL‐12 secretion, contributing to the prevention of periodontal destruction (Huck et al, 2020; Mulhall, DiChiara, et al, 2020). In this study, beyond validating our previous results, we also observed that pasteurized A. muciniphila led to comparable local and systemic anti‐inflammatory effects in both lean and obese animals.…”

“…Akkermansia muciniphilia , a novel probiotic, has been shown to counteract P. gingivalis‐ induced tissue damage, especially alveolar bone loss, in models of experimental periodontitis (Huck et al, 2020; Mulhall, DiChiara, et al, 2020). This muciniphilic gram‐negative bacterium is found throughout the gastrointestinal tract.…”

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites

“…The gene coding for Amuc_1100 can be transferred into Escherichia coli, which then acquires Akk-like features with respect to the suppression of obesity [30]. Moreover, recombinant Amuc_1100 has antiobesity [18] as well as anti-inflammatory effects in mice, for example in mouse models of colitis [31] and experimental periodontitis [32]. A clinical study that compared the effects of pasteurized versus live Akk led to the conclusion that the pasteurized bacterium was more efficient than the live one [19].…”