Gut microbial metabolites reveal diet-dependent metabolic changes induced by nicotine administration

The gut microbiota has emerged as an important factor that potentially
influences various physiological functions and pathophysiological
processes such as obesity and type 2 diabetes mellitus. Accumulating
evidence from human and animal studies suggests that gut microbial
metabolites play a critical role as integral molecules in host–microbe
interactions. Notably, several dietary environment-dependent fatty acid
metabolites have been recognized as potent modulators of host metabolic
homeostasis. More recently, nicotine, the primary active molecule in
tobacco, has been shown to potentially affect host metabolism through
alterations in the gut microbiota and its metabolites. However, the
mechanisms underlying the interplay between host nutritional status,
diet-derived microbial metabolites, and metabolic homeostasis during
nicotine exposure remain unclear. Our findings revealed that nicotine
administration had potential effects on weight regulation and metabolic
phenotype, independent of reduced caloric intake. Moreover,
nicotine-induced body weight suppression is associated with specific
changes in gut microbial composition, including Lactobacillus spp., and
KetoB, a nicotine-sensitive gut microbiota metabolite, which could be
linked to changes in host body weight, suggesting its potential role in
modulating host metabolism. Our findings highlight the remarkable impact
of the interplay between nutritional control and the gut environment on
host metabolism during smoking and smoking cessation.