Aim: Akkermansia muciniphila is a beneficial gut commensal, whose anti-inflammatory properties have recently been demonstrated. This study aimed to evaluate the effect of A. muciniphila on Porphyromonas gingivalis elicited inflammation. Material and Methods:In lean and obese mice, A. muciniphila was administered in P. gingivalis-induced calvarial abscess and in experimental periodontitis model (EIP).Bone destruction and inflammation were evaluated by histomorphometric analysis.In vitro, A. muciniphila was co-cultured with P. gingivalis, growth and virulence factor expression was evaluated. Bone marrow macrophages (BMMϕ) and gingival epithelial cells (TIGK) were exposed to both bacterial strains, and the expression of inflammatory mediators, as well as tight junction markers, was analysed. Results: In a model of calvarial infection, A. muciniphila decreased inflammatory cell infiltration and bone destruction. In EIP, treatment with A. muciniphila resulted in a decreased alveolar bone loss. In vitro, the addition of A. muciniphila to P. gingivalisinfected BMMϕ increased anti-inflammatory IL-10 and decreased IL-12. Additionally, A. muciniphila exposure increases the expression of junctional integrity markers such as integrin-β1, E-cadherin and ZO-1 in TIGK cells. A. muciniphila co-culture with P. gingivalis reduced gingipains mRNA expression. Discussion: This study demonstrated the protective effects of A. muciniphila administration and may open consideration to its use as an adjunctive therapeutic agent to periodontal treatment. K E Y W O R D S infection, inflammation, periodontitis, probiotic | 203 HUCK et al.

Babesiosis is a tick-borne zoonosis caused by protozoans of the genus Babesia; apicomplexan parasites that replicate within erythrocytes. However, unlike related Plasmodium species, the pathogenesis of Babesia infection remains poorly understood. The primary etiological agent of babesiosis in the US is B. microti. In healthy individuals, tick transmitted infection with Babesia causes no specific clinical manifestations, with many having no symptoms at all. However, even in asymptomatic people, a Babesia carriage state can be established that can last up to a year or more. Current blood bank screening methods do not identify infected donors, and Babesia parasites survive blood banking procedures and storage. Thus, Babesia can also be transmitted by infected blood, and is currently the number one cause of reportable transfusion transmitted infection in the US. Despite a significant impact on human health, B. microti remains understudied. Here, we evaluated the course of Babesia infection in three different strains of mice, C57BL/6J, BALB/cJ and C3H-HeJ, and examined the contribution of multiple immune parameters including: toll-like receptors, B cells, CD4+ cells, IFN-γ, and nitric oxide on the level of parasitemia and parasite clearance during acute babesiosis. We found that B. microti reaches high parasitemia levels during the first week of infection in all three mice strains before resolving spontaneously. Our results indicate that resolution of babesiosis requires CD4 T cells and a novel mechanism of parasite killing within infected erythrocytes.

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.

Periodontitis is an inflammatory disease associated with a dysbiosis of the oral flora characterized by a chronic sustained inflammation leading to destruction of tooth-supporting tissues. Over the last decade, an association between periodontitis and systemic disorders such as cardiovascular diseases, rheumatoid arthritis and obesity has been demonstrated. The role of periodontal pathogens, notably Porphyromonas gingivalis (P. gingivalis), in the onset or exacerbation of systemic diseases has been proposed. P. gingivalis expresses several virulence factors that promote its survival, spreading, and sustaining systemic inflammation. Recently, the impact of periodontitis on gut dysbiosis has also been suggested as a potential mechanism underlying the systemic influence of periodontitis. New therapeutic strategies for periodontitis and other dysbiotic conditions, including the use of beneficial microbes to restore healthy microbial flora, may pave the way to improved therapeutic outcomes and more thorough patient management.

Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu31Pro34]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 μg/rat), a low (68 μg /rat), or high (132 μg/rat) dose of [Leu31Pro34]NPY or vehicle immediately following the last SPS stressor, left undisturbed for 1 week and then tested for depressive-like behavior together with naïve unstressed controls. Vehicle treated animals had elevated immobility forced swim test (FST) and reduced sucrose preference, which were not observed in animals given NPY or the higher dose of [Leu31Pro34]NPY. This dose of [Leu31Pro34]NPY, like NPY, also prevented the SPS-elicited induction of CRF mRNA in the mediobasal hypothalamus. However, [Leu31Pro34]NPY did not prevent, but rather enhanced, the SPS-triggered induction of GR and FKBP5 mRNA levels in the mediobasal hypothalamus. Thus, [Leu31Pro34]NPY may be as effective as NPY and displays therapeutic potential for preventing development of depressive-like behaviors and dysregulation of the CRF/HPA system in PTSD. However, due to its different effects compared to NPY on GR and FKBP5 a broader agonist, such as NPY, may be more desirable.