The colonic microbiome is essential in human health and disease. Clostridium
difficile-associated diarrhea (CDAD), a highly morbid form of infectious diarrhea, is caused
by antibiotics which perturb the microbiome and allow C. difficile to proliferate. Proton
pump inhibitors (PPIs) are powerful suppressors of gastric acid and among the most common
medicines in the United States. Dozens of observational studies show that longterm PPI use is
associated with CDAD. However, the mechanism by which PPIs cause CDAD is unknown. We believe
that PPIs cause CDAD by inducing alterations in the human colonic microbiome. We will confirm
or refute the hypothesized mechanism for the association between PPIs and CDAD using an
unblinded, single-armed study design. We will use pyrosequencing of the hypervariable V4
region of the bacterial 16S ribosomal subunit gene in human fecal samples to describe the
colonic flora. We will collect fecal samples from volunteers before and after PPIs given for
different durations and test the microbiome to determine 1) whether PPIs diminish overall
diversity, 2) whether PPIs diminish relative abundance of Bacteroidetes, 3) whether increased
duration of PPIs affects diversity, and 4) whether there is recovery of diversity after
completing a defined course of PPIs. We believe that PPIs will cause a pattern of diminished
overall microbiome diversity and reduced anaerobes - the same pattern seen after use of
antibiotics. Furthermore, we believe that increased PPI duration will further diminish
diversity and that the microbiome will return to pre-PPI levels of diversity after PPIs are
stopped. These results will facilitate biologically-based clinical interventions to reduce
rates of CDAD among patients who require acid suppression.