Temporal profile of germ-free and conventionally raised male mice (DUODENUM and ILEUM)

Gut microbiota and the circadian clock both regulate metabolism. The circadian clock and associated feeding rhythms were shown to impact on the microbial community. However, to what extent gut microbiota reciprocally affect daily rhythms of gene expression and physiology in the host remains elusive. Here, we analyzed the transcriptomes of male and female germ-free mice. While this revealed subtle changes in circadian clock gene expression in liver, intestine, and white adipose tissue, germ-free mice showed considerably altered expression of genes associated to rhythmic physiology. Strikingly, absence of microbiome severely compromised liver sex-dimorphism at the transcriptome and metabolome level. Their sex-specific rhythmicity was strongly attenuated. The resulting feminization of male and masculinization of female hepatic gene expression in germ-free animals is likely caused by altered sex-dimorphism in sex and growth hormone secretion, linked to differential activation of xenobiotic receptors. This defines a novel mechanism by which the gut microbiome regulates host metabolism. Total RNA-Seq of conventional raised (convR) and Germ-free (GF) male under ad libitum feeding regime. Temporal mRNA profiles of duodenum and ileum were assessed every 4 hours during the diurnal cycle (Zeitgerber time (ZT) 2-22).肠道菌群与生物钟二者共同调控宿主代谢。已有研究证实，生物钟及其关联的进食节律可影响微生物群落结构。然而，肠道菌群能够在多大程度上反向调控宿主的基因表达昼夜节律与生理节律，目前仍尚不明确。 本研究对雌雄无菌小鼠（germ-free mice）的转录组进行了分析。尽管仅在肝脏、肠道与白色脂肪组织中观察到生物钟基因表达的细微变化，但无菌小鼠体内与节律性生理功能相关的基因表达却发生了显著改变。值得注意的是，无菌状态（即肠道菌群缺失）会严重破坏肝脏在转录组与代谢组层面的性别二态性，其性别特异性节律性显著减弱。无菌动物中雄性肝脏基因表达的雌性化与雌性肝脏基因表达的雄性化，可能源于性激素与生长激素分泌的性别二态性改变，而这一改变与异生物质受体（xenobiotic receptors）的差异化激活密切相关。该研究揭示了肠道菌群调控宿主代谢的全新机制。 本研究对自由进食条件下的常规饲养（conventional raised, convR）与无菌（Germ-free, GF）雄性小鼠开展了全转录组RNA测序。在昼夜周期内，以泽时间（Zeitgerber time, ZT）2至22为采样节点，每4小时采集一次十二指肠与回肠的时序mRNA表达谱。