1. Host-derived nitrate promotes Trymethylamine (TMA) production by gut microbiota during High Fat (HF) diet

  1. Elucidate the mechanism by which HF diet induces production of inducible nitric oxide (iNOS) by intestinal epithelial cells
  2. Determine how HF diet induces gut dysbiosis and bloom of Enterobacteriaceae
  3. Determine how HF diet induced gut dysbiosis promotes increased production of TMA by Enterobacteriaceae leading to increased risk of heart disease

2. Understanding mechanisms of antibiotic-induced weight gain

  1. Determine how antibiotic treatment (low dose penicillin) affects colonic epithelium metabolism leading to intestinal dysbiosis
  2. Determine if antibiotic treatment affects PPARg signaling in intestinal epithelial cells leading to weight gain
  3. Determine if the effects of antibiotic treatment can be reversed by treating mice with 5-aminosalicylic acid

3. Linking Inflammatory Bowel Disease (IBD) and colonic epithelial metabolism

  1. Determine if colonic inflammation induces a metabolic shift in colonic epithelial cells
  2. Determine if the metabolic shift is dependent on the nuclear receptor PPARg
  3. Elucidate the mechanisms by which changes in colonic epithelial metabolism during colitis lead to bloom of colon cancer-associated Enterobacteriaceae
  4. Determine if targeting of colonic epithelium metabolism can prevent inflammation-associated colon cancer.