Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

Propionate is a microbial metabolite that is formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing—one that can oxidize ferredoxin and reduce NAD. Here we show that Rnf [ferredoxin--NAD(+) oxidoreductase (Na(+)-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevisandPrevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. At first, this pathway appears unbalanced, forming reduced ferredoxin and oxidized NAD in excess. If this continued unabated, fermentation would halt within 1.5 s. We found these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf. This is demonstrated using growth experiments, genomics, proteomics, and enzyme assays. Genomic and phenotypic data suggest many bacteria use Rnf similarly. We cataloged fermentation products of >1,400 species of prokaryotes, and nearly 10% formed propionate, succinate, and acetate. Over 40% of species carrying out this fermentation also had genes for Rnf. This work shows Rnf is important to propionate formation in many bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.