Ramos Stephany Flores, Siguenza Nicole, Zhong Wuling, Mohanty Ipsita, Lingaraju Amulya, Richter R Alexander, Karthikeyan Smruthi, Lukowski April L, Zhu Qiyun, Nunes Wilhan D G, Zemlin Jasmine, Xu Zhenjiang Zech, Hasty Jeff, Dorrestein Pieter C, Panda Satchidananda, Knight Rob, Zarrinpar Amir
Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA.
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Cell Host Microbe. 2025 Jul 9;33(7):1057-1072. doi: 10.1016/j.chom.2025.05.024. Epub 2025 Jun 18.
Diurnal rhythmicity in the gut maintains gut integrity, circadian rhythms, and metabolic homeostasis. However, existing studies focus on microbial composition rather than transcriptional activity. To understand microbial functional dynamics, we characterize diurnal fluctuations in the mouse cecal metatranscriptome and metagenome under high-fat diet and time-restricted feeding (TRF). We show that metatranscriptomics uncover TRF-induced time-dependent microbial functional shifts that are undetectable with metagenomics alone. We also found bile salt hydrolase () from exhibits diurnal expression in the TRF group. Engineering this , along with other candidates, into a native chassis reveals distinct differences in deconjugation and amidation activities, underscoring functional specificity. , a improves insulin sensitivity, glucose tolerance, and body composition, suggesting a direct role in TRF metabolic benefits. This study highlights how coupling metatranscriptomics with engineered bacterial systems is a powerful approach for uncovering time-dependent bacterial functions related to health and disease.
肠道中的昼夜节律维持肠道完整性、昼夜节律和代谢稳态。然而，现有研究集中在微生物组成而非转录活性上。为了解微生物功能动态，我们对高脂饮食和限时喂养（TRF）条件下小鼠盲肠元转录组和宏基因组的昼夜波动进行了表征。我们发现元转录组学揭示了TRF诱导的时间依赖性微生物功能转变，而仅靠宏基因组学无法检测到这些转变。我们还发现来自[具体物种]的胆汁盐水解酶（[具体名称]）在TRF组中呈现昼夜表达。将这种[具体名称]以及其他候选物构建到天然[底盘细菌名称]底盘中，揭示了在去共轭和酰胺化活性方面的明显差异，突出了功能特异性。[具体细菌名称]，一种[细菌类型]，可改善胰岛素敏感性、葡萄糖耐量和身体组成，表明其在TRF代谢益处中发挥直接作用。这项研究强调了将元转录组学与工程细菌系统相结合是揭示与健康和疾病相关的时间依赖性细菌功能的有力方法。
