Kombucha Tea-associated Microbes Remodel Host Metabolic Pathways to Suppress Lipid Accumulation

Abstract

The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintainC. eleganson a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture. KT microbes robustly colonize the gut of KTM-fed animals and confer normal development and fecundity. Intriguingly, animals consuming KTMs display a marked reduction in total lipid stores and lipid droplet size. We find that the reduced fat accumulation phenotype is not due to impaired nutrient absorption, but rather it is sustained by a programed metabolic response in the intestine of the host. KTM consumption triggers widespread transcriptional changes within core lipid metabolism pathways, including upregulation of a suite of lysosomal lipase genes that are induced during lipophagy. The elevated lysosomal lipase activity, coupled with a decrease in lipid droplet biogenesis, is partially required for the reduction in host lipid content. We propose that KTM consumption stimulates a fasting- like response in theC. elegansintestine by rewiring transcriptional programs to promote lipid utilization. Our results provide mechanistic insight into how the probiotics in Kombucha Tea reshape host metabolism and how this popular beverage may impact human metabolism.

The TWK-26 potassium channel governs nutrient absorption in theC. elegansintestine

“…Quantification of Oil Red O staining was conducted by manually outlining worms in ImageJ (Schindelin et al 2012) and then measuring the mean gray value within the area of each worm. These values were subtracted from the maximum gray value for 16-bit images, 65,526, as previously described (DuMez-Kornegay et al 2024). Data were plotted and analyzed using Prism 9.…”

Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis

“…Subsequently, the animals were washed in M9, mounted on a 2% agarose pad, and immediately imaged with a Nikon Ti2 widefield microscope equipped with a Hamamatsu ORCA-Fusion BT camera. Quantification of Oil Red O and Nile Red was performed in Fiji exactly as previously described 63 . Data were plotted using Prism 9 and a one-way ANOVA with a Bonferroni correction was performed to calculate statistical significance.…”