Periodontitis-related salivary microbiota aggravates Alzheimer's disease via gut-brain axis crosstalk.

The oral cavity is the initial chamber of digestive tract; the saliva swallowed daily contains an estimated 1.5 × 1012 oral bacteria. Increasing evidence indicates that periodontal pathogens and subsequent inflammatory responses to them contribute to the pathogenesis of Alzheimer's disease (AD). The intestine and central nervous system jointly engage in crosstalk; microbiota-mediated immunity significantly impacts AD via the gut-brain axis. However, the exact mechanism linking periodontitis to AD remains unclear. In this study, we explored the influence of periodontitis-related salivary microbiota on AD based on the gut-brain crosstalk in APPswe/PS1ΔE9 (PAP) transgenic mice. Saliva samples were collected from patients with periodontitis and healthy individuals. The salivary microbiota was gavaged into PAP mice for two months. Continuous gavage of periodontitis-related salivary microbiota in PAP mice impaired cognitive function and increased ß-amyloid accumulation and neuroinflammation. Moreover, these AD-related pathologies were consistent with gut microbial dysbiosis, intestinal pro-inflammatory responses, intestinal barrier impairment, and subsequent exacerbation of systemic inflammation, suggesting that the periodontitis-related salivary microbiota may aggravate AD pathogenesis through crosstalk of the gut-brain axis. In this study, we demonstrated that periodontitis might participate in the pathogenesis of AD by swallowing salivary microbiota, verifying the role of periodontitis in AD progression and providing a novel perspective on the etiology and intervention strategies of AD.

Salivary microbiota of periodontitis aggravates bone loss in ovariectomized rats.

The mechanisms underlying the crosstalk between periodontitis and osteoporosis remain unclear. Recently, the gut microbiota has been recognized as a pivotal regulator of bone metabolism, and oral and gut mucosae are microbiologically connected. In this study, we investigated the effects of periodontitis on osteoporosis through the oral-gut axis. The salivary microbiota of patients with periodontitis was collected and then pumped into the intestine of Sprague-Dawley rats via intragastric administration for 2 weeks. An osteoporosis model was established using ovariectomy. Changes in the maxillae and femora were evaluated using microcomputed tomography (micro CT) and HE staining. Intestinal barrier integrity and inflammatory factors were examined using real-time quantitative polymerase chain reaction and immunofluorescence. The gut microbiota was profiled by 16S rRNA gene sequencing. Metabolome profiling of serum was performed using liquid chromatography-mass spectrometry sequencing. Micro CT and HE staining revealed osteoporotic phenotypes in the maxillae and femora of ovariectomized (OVX) rats. Our results confirmed that the salivary microbiota of patients with periodontitis aggravated femoral bone resorption in OVX rats. In addition, intestinal inflammation was exacerbated after periodontitis salivary microbiota gavage in OVX rats. Correlation analysis of microbiota and metabolomics revealed that lipolysis and tryptophan metabolism may be related to the bone loss induced by the salivary microbiota of patients with periodontitis. In conclusion, periodontitis can aggravate long bone loss through the oral-gut axis in OVX rats.

Periodontitis may impair the homeostasis of systemic bone through regulation of gut microbiota in ApoE-/- mice.

AIM: To investigate whether periodontitis impacts bone homeostasis via gut microbiota regulation. MATERIALS AND METHODS: Experimental periodontitis was induced by ligatures (LIG group). ApoE-/- mice were employed as a model with weakened bone homeostasis. Bone turnover was evaluated through micro-computerized tomography, haematoxylin and eosin-stained sections, osteoblast and osteoclast biomarkers in the bone and serum. Gut microbiota was analysed through 16S ribosomal RNA gene sequencing. Serum concentrations of cytokines were detected by enzyme-linked immunosorbent assay. The role of gut microbiota was evaluated through their transplantation into antibiotic-treated mice. RESULTS: Periodontitis significantly increased the number of osteoclasts and the expression of the osteoclast biomarkers in the proximal tibia of ApoE-/- mice, with the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) ratio significantly increased, which indicated the osteoclastic activity overwhelmed osteogenesis. Meanwhile, periodontitis altered the composition of gut microbiota and induced low-grade inflammation in the colon and blood circulation. Interestingly, the concentration of circulating tumour necrosis factor-α, interleukin (IL)-6, IL-1ß, IL-17A, and monocyte chemotactic factor-1 were positively correlated with faecal α1-antitrypsin and calprotectin, as well as serum OPG and RANKL. Furthermore, transplantation of gut microbiota from mice with periodontitis to antibiotic-treated mice could partially re-capitulate the phenotypes in the bone and colon. CONCLUSION: Periodontitis may impair systemic bone homeostasis through gut microbiota.

Non-surgical Periodontal Treatment Restored the Gut Microbiota and Intestinal Barrier in Apolipoprotein E-/- Mice With Periodontitis.

Periodontitis has been associated with a variety of systematic diseases via affecting gut microbiota. However, the influence of periodontal treatment on intestinal microbiota is not known. Hyperlipidemia can significantly alter gut microbiota structure. It is proposed that the presence of hyperlipidemia can influence the impact of periodontitis on microbiota. This study was conducted to explore the influence of periodontitis and periodontal treatment on the gut microbiota on the basis of hyperlipidemia. Apolipoprotein E-/-(ApoE-/-) mice were ligatured to induced periodontitis and non-surgical periodontal treatment was performed for half of them after 4 weeks of ligation. Microbiota communities in the feces collected at 4, 5, 8 weeks after ligation were investigated using next-generation sequencing of 16S rDNA. Bone loss at periodontitis sites were analyzed using micro-computed tomography (Micro-CT). Morphology and mucosal architecture injury of ileum tissue were observed with hematoxylin-eosin staining. The serum lipid levels were assayed. The results showed that ß-diversity index in experimental periodontitis group was differed significantly from that of the control group. Significant differences were found in ß-diversity between the non-surgical periodontal treatment group and the ligation group. The samples of the non-surgical periodontal treatment group and the control group were clustered together 4 weeks after periodontal treatment. Intestinal villus height and ratio of villus height to crypt depth was found decreased after ligation and restored after non-surgical periodontal treatment. Non-surgical periodontal treatment induced the colonization and prosper of butyrate-producing bacteria Eubacterium, which was absent/not present in the ligation group. We confirmed that periodontitis led to gut microbiota dysbiosis in mice with hyperlipidemia. Non-surgical periodontal treatment had the trend to normalize the gut microbiota and improved the intestinal mucosal barrier impaired by periodontitis in apoE-/- mice.