Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed ( n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro–computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography–mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage ( P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone ( P < 0.05). These key genera were correlated with BV/TV and BV ( P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera ( P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut–blood–bone axis.

中文翻译：

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鼠李糖乳杆菌 GG 通过肠血轴改善高脂血症的牙周骨修复

牙周骨再生仍然是临床挑战，高脂血症会加剧牙槽骨吸收。最近有报道称益生菌可以改善骨量。我们的目的是确定鼠李糖乳酸杆菌 GG (LGG) 在牙周炎伴高脂血症的情况下改善牙周骨再生的作用。构建牙周炎、高脂血症和牙周开窗缺陷的 Sprague Dawley 大鼠模型（n = 36）并给予 LGG 灌胃 6 周（随后处死大鼠）。LGG 灌胃后 3 周，将供体大鼠的粪便微生物群移植到受体大鼠体内，以评估 LGG 调节的肠道微生物群在牙周骨再生中的作用。使用微型计算机断层扫描和苏木精和伊红染色检测再生骨量。使用 16S 核糖体 RNA 测序分析肠道微生物群。通过液相色谱-质谱法检测血清代谢物（LGG 灌胃后 6 周）。筛选的血清代谢物的促骨作用在体外对骨髓间充质干细胞（BMMSC）进行了验证。我们发现，LGG灌胃后再生牙周骨的骨密度、骨体积（BV）、骨小梁体积分数（BV/TV）和小梁厚度均有所增加（P < 0.05），但对口腔菌群影响不大。LGG灌胃后，供者肠道内的葡萄球菌、棒状杆菌和柯林氏菌发生显着变化，受者肠道中也保持了这些差异，且再生牙周骨小梁厚度增加（ P < 0.05）。这些关键属与 BV/TV 和 BV 相关（ P < 0.05）。此外，LGG灌胃显着调节骨相关血液代谢物，其中硒代蛋氨酸促进BMMSC成骨。值得注意的是，硒代蛋氨酸与关键肠道属相关（P < 0.05）。总的来说，LGG 通过调节肠道微生物群和增加血液中的促成骨代谢物，改善了牙周炎伴高脂血症的牙周骨再生。这些结果揭示了使用益生菌通过肠-血-骨轴促进牙周骨再生的新见解。