High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease





Jee-Yon Lee, Stephanie A. Cevallos, Mariana X. Byndloss, Connor R. Tiffany, Erin E. Olsan, Brian P. Butler, Briana M. Young, Andrew W.L. Rogers, Henry Nguyen,Kyongchol Kim, Sang-Woon Choi, Eunsoo Bae, Je Hee Lee, Ui-Gi Min, Duk-Chul Lee, Andreas J. Bäumler


Cell host & microbe, [Online ahead of print], doi: 10.1016/j.chom.2020.06.001


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.


- PMID: 32668218


- Fulltext: https://www.sciencedirect.com/science/article/abs/pii/S1931312820303036?via%3Dihub