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 maintain C. elegans on 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 the C. elegans intestine 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.
摘要:
古代的流行,富含益生菌的饮料康普茶(KT)在一定程度上由于其所谓的健康益处而激增,其中包括预防代谢性疾病;然而,这些说法尚未经过严格测试,宿主对KT中益生菌的应答机制尚不清楚.这里,我们建立了一种可重复的方法来维持秀丽隐杆线虫的饮食,该饮食仅由康普茶相关微生物(KTM)组成,这反映了发酵培养物中发现的微生物群落。KT微生物在KTM喂养的动物的肠道中强劲定殖,并赋予正常的发育和繁殖力。有趣的是,食用KTM的动物显示出总脂质存储和脂滴大小的显着减少。我们发现脂肪积累减少的表型不是由于营养吸收受损,而是通过宿主肠道中的程序化代谢反应来维持。KTM消耗引发核心脂质代谢途径内广泛的转录变化,包括在吸脂过程中诱导的一组溶酶体脂肪酶基因的上调。溶酶体脂肪酶活性升高,再加上脂滴生物合成的减少,是减少宿主脂质含量所需的部分。我们建议KTM消耗通过重新连接转录程序以促进脂质利用来刺激秀丽隐杆线虫肠道中的禁食样反应。我们的研究结果为康普茶中的益生菌如何重塑宿主代谢以及这种流行的饮料如何影响人体代谢提供了机制见解。