Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are currently under development to extend the key metabolic therapeutic actions of trehalose without adversely affecting host microbial communities. In the current study, we contrast the extent to which trehalose and its degradation-resistant analogue, lactotrehalose (LT), modulate microbial communities and host transcriptomic profiles. We demonstrate that trehalose and LT each exert adaptive metabolic and microbial effects that both overlap and diverge. We postulate that these effects depend both upon compound stability and bioavailability, and on stereospecific signal transduction. In context, the data suggest that trehalose is unlikely to be harmful, and yet it harbors unique effects that are not yet fully replicated by its analogues. These compounds are thus valuable probes to better define trehalose structure-function, and to offer as therapeutic metabolic agents.
Keywords: Clostridioides difficile; NAFLD; lactotrehalose; microbiome; trehalose.