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 β-diversity index in experimental periodontitis group was differed significantly from that of the control group. Significant differences were found in β-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 butyrateproducing 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.

Evidence suggests that periodontitis contributes to the pathogenesis of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. However, few studies have examined the role of swallowing and saliva in the pathogenesis of gastrointestinal diseases. Saliva contains an enormous number of oral bacteria and is swallowed directly into the intestine. Here, we explored the influence of periodontitis salivary microbiota on colonic inflammation and possible mechanisms in dextran sulfate sodium (DSS)–induced colitis. The salivary microbiota was collected from healthy individuals and those with periodontitis and gavaged to C57BL/6 mice. Periodontitis colitis was induced by DSS for 5 d and ligature for 1 wk. The degree of colon inflammation was evaluated through hematoxylin and eosin staining, ELISA, and quantitative real-time polymerase chain reaction. Immune parameters were measured with quantitative real-time polymerase chain reaction, flow cytometry, and immunofluorescence. The gut microbiota and metabolome analyses were performed via 16S rRNA gene sequencing and liquid chromatography–mass spectrometry. Although no significant colitis-associated phenotypic changes were found under physiologic conditions, periodontitis salivary microbiota exacerbated colitis in a periodontitis colitis model after DSS induction. The immune response more closely resembled the pathology of ulcerative colitis, including aggravated macrophage M2 polarization and Th2 cell induction (T helper 2). Inflammatory bowel disease–associated microbiota, such as Blautia, Helicobacter, and Ruminococcus, were changed in DSS-induced colitis after periodontitis salivary microbiota gavage. Periodontitis salivary microbiota decreased unsaturated fatty acid levels and increased arachidonic acid metabolism in DSS-induced colitis, which was positively correlated with Aerococcus and Ruminococcus, suggesting the key role of these metabolic events and microbes in the exacerbating effect of periodontitis salivary microbiota on experimental colitis. Our study demonstrated that periodontitis contributes to the pathogenesis of colitis through the swallowing of salivary microbiota, confirming the role of periodontitis in systemic disease and providing new insights into the etiology of gastrointestinal inflammatory diseases.

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Aim: To investigate whether periodontitis impacts bone homeostasis via gut microbiota regulation.Materials and Methods: Experimental periodontitis was induced by ligatures (LIG group). ApoE À/À 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 À/À 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-1β, 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.

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.