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

Cell Host Microbe. 2020 Aug 12;28(2):273-284.e6. doi: 10.1016/j.chom.2020.06.001. Epub 2020 Jul 14.


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.

Keywords: antibiotics; dysbiosis; high-fat diet; inflammatory bowel disease; irritable bowel syndrome; microbiota.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Diet, High-Fat / adverse effects*
  • Dysbiosis / chemically induced
  • Dysbiosis / pathology*
  • Energy Metabolism / physiology*
  • Enterobacteriaceae / growth & development
  • Gastrointestinal Microbiome
  • Humans
  • Inflammatory Bowel Diseases / microbiology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Irritable Bowel Syndrome / microbiology*
  • Leukocyte L1 Antigen Complex / metabolism
  • Mesalamine / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • PPAR gamma / agonists


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Leukocyte L1 Antigen Complex
  • PPAR gamma
  • Pparg protein, mouse
  • Mesalamine