Trehalose is a disaccharide that might be used in treatment of cardiometabolic diseases. However, trehalose consumption promotes expansion of Clostridioides difficile ribotypes that metabolize trehalose via trehalose-6-phosphate hydrolase (treA). Furthermore, brush border and renal trehalases can reduce the efficacy of trehalose by cleaving it into monosaccharides. We investigated whether a trehalase-resistant analogue of trehalose (lactotrehalose) has the same metabolic effects of trehalose without expanding C difficile.