Porphyromonas gingivalis impairs glucose uptake in skeletal muscle associated with altering gut microbiota

• Published in: The FASEB journal Vol. 35; no. 2; p. e21171
• Main Authors: Watanabe, Kazuki, Katagiri, Sayaka, Takahashi, Hirokazu, Sasaki, Naoki, Maekawa, Shogo, Komazaki, Rina, Hatasa, Masahiro, Kitajima, Yoichiro, Maruyama, Yusuke, Shiba, Takahiko, Komatsu, Keiji, Ohsugi, Yujin, Tanaka, Kenichi, Matsuzawa, Ayumi, Hirota, Tomomitsu, Tohara, Haruka, Eguchi, Yuichiro, Anzai, Keizo, Hattori, Atsuhiko, Iwata, Takanori
• Format: Journal Article
• Language: English
• Published: United States 01.02.2021
• Subjects: Porphyromonas gingivalis; metabolic syndrome; glucose uptake; skeletal muscle; periodontal disease
• ISSN: 1530-6860
• DOI: 10.1096/fj.202001158R

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.