Investigating the effect of ginger-derived nanovesicles on the growth and metabolic activity of <i>Bacteroides thetaiotaomicron</i> : an isothermal microcalorimetric study

Abstract Plant-derived extracellular vesicles (EVs) have shown numerous health benefits, including modulation of the human gut microbiota. Hereby, we employed isothermal microcalorimetry (IMC) to explore the effects of ginger-derived nanovesicles (G-NVs) on the growth and metabolic activity of Bacteroides thetaiotaomicron (Bt), a dominant saccharolytic commensal with promising next-generation probiotic potential. Bt was exposed to either G-NVs or the ginger extract separated from G-NVs (G-CTL) in defined media under anaerobic conditions. Both ginger samples enhanced bacterial specific growth rate and maximum metabolic activity, inducing the latter earlier. However, higher biomass production and greater secretion of acetic, succinic, and propionic acids occurred only in response to the G-CTL. Complete sugar depletion and unchanged FAA levels indicated preferential carbohydrate utilization by Bt . Overall, these findings revealed that Bt ’s metabolic state is shaped by both G-NVs and G-CTL, yet through distinct mechanisms, with G-NVs inducing rapid stimulation without increasing total metabolic output and G-CTL providing a sustained, dose-dependent effect. To our knowledge, this is the first study applying IMC to monitor real-time the impact of EVs on microbial growth and metabolism, underscoring IMC’s utility for mechanistic studies of EV-microbe interactions. Furthermore, this research sets the ground for innovative strategies in nutraceutical and microbiome-targeted therapy development.