Cell Host and Microbe
[IF:15.923]
High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease
高脂饮食和抗生素协同损害线粒体生物能，触发菌群失调，加剧前驱炎症性肠病
10.1016/j.chom..06.001
07-14, Article
Abstract & Authors:
Abstract:
The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator–activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.
First Authors:
Jee-Yon Lee
Correspondence Authors:
Andreas J Bäumler
All Authors:
Jee-Yon Lee,Stephanie A Cevallos,Mariana X Byndloss,Connor R Tiffany,Erin E Olsan,Brian P Butler,Briana M Young,Andrew WL Rogers,Henry Nguyen,Kyongchol Kim,Sang-Woon Choi,Eunsoo Bae,Je Hee Lee,Ui-Gi Min,Duk-Chul Lee,Andreas J Bäumler
