Project description:Kombucha Tea (KT), a fermented tea with roots in traditional Chinese medicine, has surged in worldwide popularity due to its purported health benefits. KT contains a symbiotic culture of yeast and bacterial species, many of which are considered human probiotics. The molecular basis of the health benefits of KT has yet to be thoroughly explored in any animal model. We establishC. elegansas a model to query the molecular interactions between Kombucha-associated microbes (KTM) and the host. We find that worms have an established gut microbiome after consuming a KTM-exclusive diet that mirrors the microbial community found in the fermenting culture. Remarkably, animals consuming KTMs display strikingly reduced lipid levels, yet develop and reproduce similarly toE. coli-fed animals. Critically, consumption of a non-fermenting mix of KT microbial isolates (Kombucha microbe mix) resulted in elevated fat accumulation, suggesting that KTMs do not impair nutrient absorption. To identify the host metabolic pathways altered by KTMs, we performed mRNA-seq on KTM-fed animals, finding widespread changes in lipid metabolism genes. Specifically, we found that three lysosomal lipase genes are significantly upregulated in these animals. These lipases, LIPL-1-3, have been previously shown to promote lipophagy via catabolism of lipid droplets. Consistently, KTM-fed animals display reduced levels of triglycerides and smaller lipid droplet sizes. We propose that KTM-fed animals exhibit a fasting-like metabolic state, even in the presence of sufficient nutrient availability, possibly through induction of lipophagy. Elucidating the host metabolic response to KT consumption will provide unprecedented insight into how this popular fermented beverage may impact human health and inform its use in complementary healthcare plans.