Elucidating the Host Metabolic Response to Consumption of Kombucha-associated Microorganisms

PROJECT SUMMARY
Kombucha is a popular fermented tea that contains probiotics. This beverage has seen a surge in popularity in
the United States since the turn of the century and is purported to have many health benefits. Some of these
health claims have been cursorily examined, however, none have been rigorously tested and the mechanistic
interactions between the microbial components of Kombucha and the host remains unexplored. I will elucidate
the host metabolic response to consumption of Kombucha-associated microbes (K. microbes), thereby informing
its use in complementary health approaches. The impact of individual probiotic microbes on human health is
difficult to deconvolute as humans consume a complex diet, have trillions of gut microbes (including many
unidentified species), and measuring host-microbe interactions is not feasible in human subjects. Therefore,
animal model systems are essential to investigate the effects of consuming probiotics, including those in
Kombucha, on host physiological processes. Caenorhabditis elegans is an excellent model system to explore
how K. microbes modulate the host pathways that govern lipid homeostasis, because their microbiomes are
easily manipulated through the food source provided and they are a well-established system to study metabolism
and the aging process in vivo. I have established a standardized method to maintain C. elegans on a diet
exclusively consisting of K. microbes that is consistent with the community found in the fermenting culture
(confirmed through 16S rRNA sequencing). In preliminary investigations, I observed that populations of C.
elegans exclusively consuming K. microbes, as compared to a control diet (E. coli, the standard laboratory food
source), have altered expression of core lipid metabolism genes (e.g., beta-oxidation, fatty acid desaturation),
decreased fat levels, and an increased median lifespan. Critically, the molecular mechanisms by which K.
microbes alter host physiology is completely unknown. Therefore, I plan to use molecular and genetic
approaches in C. elegans to systematically identify the molecular mechanisms that govern the host response to
K. microbe consumption and elucidate the components of Kombucha that are necessary and sufficient to confer
the observed metabolic and lifespan phenotypes. The proposed experiments will provide unprecedented insight
into the mechanism by which K. microbe consumption reconfigures host metabolism.