High-Fat Diet, Dysbiosis, and Gastrointestinal and Colonic Transit: Is There a Missing Link?

n a series of elegant studies reported in this issue of ICellular and Molecular Gastroenterology and Hepatology, Anitha et al report that a high-fat diet results in slowing of gastrointestinal transit (by geometric center of fluorescein isothiocyanate distribution after gavage), total gastrointestinal transit (by first arrival of a blue dye in stool), and distal colonic transit (by the time taken to expel a bead through the last 2 cm of colon). This retardation of transit is associated with increased numbers of fecal Firmicutes and reduced numbers of Bacteroidetes. The high-fat diet also was associated with an increase in serum lipopolysaccharide, reflecting increased permeability of the digestive tract, and reductions in numbers of enteric nervous system neurons, with specific loss of neurons expressing nitric oxide synthase. Anitha et al hypothesize that a reduction in nitric oxide synthase– expressing neurons was the cause of retarded transit. Oligofructose partly corrected transit rate, serum lipopolysaccharide, microbial perturbations, and a reduction in enteric nervous system nitrergic neurons. Parallel in vitro studies have suggested that dietary fat causes neuronal apoptosis by activating Toll-like receptor 4. The data provided by the animal model lead to a number of intriguing questions, some of which will require investigation in human beings while others can be addressed based on prior reports in the literature.