Porphyromonas gingivalis impairs glucose uptake in skeletal muscle associated with altering gut microbiota
Porphyromonas gingivalis impairs glucose uptake in skeletal muscle associated with altering gut microbiota
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DOI：
10.1096/fj.202001158r
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Kazuki Watanabe;Sayaka Katagiri;Hirokazu Takahashi;Naoki Sasaki;Shogo Maekawa;Rina Komazaki;Masahiro Hatasa;Yoichiro Kitajima;Yusuke Maruyama;Takahiko Shiba;Keiji Komatsu;Yujin Ohsugi;Kenichi Tanaka;Ayumi Matsuzawa;T. Hirota;H. Tohara;Yuichiro Eguchi;K. Anzai;A. Hattori;T. Iwata
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文献类型：
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作者：
Kazuki Watanabe;Sayaka Katagiri;Hirokazu Takahashi;Naoki Sasaki;Shogo Maekawa;Rina Komazaki;Masahiro Hatasa;Yoichiro Kitajima;Yusuke Maruyama;Takahiko Shiba;Keiji Komatsu;Yujin Ohsugi;Kenichi Tanaka;Ayumi Matsuzawa;T. Hirota;H. Tohara;Yuichiro Eguchi;K. Anzai;A. Hattori;T. Iwata
骨骼肌具有很高的代谢能力，在葡萄糖代谢中起着关键作用。虽然牙周病增加了代谢综合征的风险，但牙周细菌感染和骨骼肌代谢障碍之间的关系尚不清楚。我们发现代谢综合征患者的抗牙龈卟啉单胞菌(PG)抗体效价与肌内脂肪组织含量(IMAC)、空腹血糖和HOMA-IR呈正相关。在喂食高脂饮食的C57BL/6J小鼠中，口服PG(HFPg)的受试者与生理盐水(HFco)受试者相比，糖耐量、胰岛素抵抗和更高的IMAC受到损害。与HFco小鼠相比，HFPg小鼠比目鱼肌表现出脂肪渗透和较低的葡萄糖摄取，较高的TNFa表达和较低的胰岛素信号转导。基因集浓缩分析表明，肿瘤坏死因子α信号通过核因子κB基因集在小鼠比目鱼肌中得到丰富。此外，肿瘤坏死因子-α还可降低C2C12成肌细胞对葡萄糖的摄取。根据16S rRNA测序，PG给药改变了肠道微生物群，特别是通过降低Turicibacter属的丰度。PG给药后，肠道微生物群落的微生物网络发生了显著变化。我们的发现表明，PG感染是代谢综合征和骨骼肌代谢功能障碍的危险因素，通过肠道微生物群的改变。
Skeletal muscles have a high metabolic capacity, which play key roles in glucose metabolism. Although periodontal disease increases the risk of metabolic syndrome, the relationship between periodontal bacterial infection and skeletal muscle metabolic dysfunction is unclear. We found that anti‐Porphyromonas gingivalis (Pg) antibody titers positively correlated with intramuscular adipose tissue content (IMAC), fasting blood glucose, and HOMA‐IR in metabolic syndrome patients. In C57BL/6J mice fed a high‐fat diet, recipients of oral Pg (HFPg) had impaired glucose tolerance, insulin resistance, and higher IMAC compared to recipients of saline (HFco). The soleus muscle in HFPg mice exhibited fat infiltration and lower glucose uptake with higher Tnfa expression and lower insulin signaling than in HFco mice. Gene set enrichment analysis showed that TNFα signaling via NFκB gene set was enriched in the soleus muscle of HFPg mice. Moreover, TNF‐α also decreased glucose uptake in C2C12 myoblast cells in vitro. Based on 16S rRNA sequencing, Pg administration altered the gut microbiome, particularly by decreasing the abundance of genus Turicibacter. Microbial network of the gut microbiome was dramatically changed by Pg administration. Our findings suggest that infection with Pg is a risk factor for metabolic syndrome and skeletal muscle metabolic dysfunction via gut microbiome alteration.