Abstract：
Chronic consumption of a high-calorie diet coupled with an altered sleep-wake cycle causes disruption of circadian clock that can impact the gut microbiome leading to metabolic syndrome and associated diseases. Herein, we investigate the effects of a high fat high fructose diet (H) alone or in combination with photoperiodic shifts induced chronodisruption (CD) on gut microbiota of C57BL/6J male mice. Further, the merits of daily evening intraperitoneal administration of melatonin in restoring gut microbiota are studied herein. Experimental groups viz. H, CD and HCD mice recorded higher levels of serum pro-inflammatory cytokines (TNF-α and IL-6) and lower levels of the anti-inflammatory cytokine, IL-10. These findings correlate with a concomitant increase in the transcripts of TLR4, TNF-α, and IL-6 in small intestine of the said groups. A decrement in mRNA levels of Ocln, ZO-1 and Vdr in these groups implied towards an altered gut permeability. These results were in agreement with the observed decrement in percentage abundance of total gut microflora and Firmicutes: Bacteroidetes (F/B) ratio. Melatonin administration accounted for lower-level inflammation (serum and gut) along with an improvement in gut permeability markers. The total abundance of gut microflora and F/B ratio showed an improvement in all the melatonin-treated groups and the same is the highlight of this study. Taken together, our study is the first to report perturbations in gut microbiota resulting due to a combination of photoperiodic shifts induced CD and a high fat high calorie diet-induced lifestyle disorder. Further, melatonin-mediated rejuvenation of gut microbiome provides prima facie evidence of its role in improving gut dysbiosis that needs a detailed scrutiny.
摘要：
长期食用高热量饮食加上睡眠-觉醒周期的改变会导致昼夜节律中断，从而影响肠道微生物组，导致代谢综合征和相关疾病。在这里，我们研究了高脂高果糖饮食（H）单独或联合光周期变化诱导的时间破坏（CD）对C57BL/6J雄性小鼠肠道菌群的影响。Further,本文研究了每天晚上腹膜内施用褪黑激素在恢复肠道微生物群中的优点。实验组，即。H,CD和HCD小鼠记录了较高水平的血清促炎细胞因子（TNF-α和IL-6）和较低水平的抗炎细胞因子，IL-10.这些发现与TLR4，TNF-α，和所述组的小肠中的IL-6。Ocln的mRNA水平下降，这些组中的ZO-1和Vdr暗示了肠道通透性的改变。这些结果与观察到的总肠道菌群和Firmicutes：拟杆菌（F/B）比率的丰度百分比下降一致。褪黑激素的给药导致较低水平的炎症（血清和肠道）以及肠道通透性标志物的改善。肠道菌群的总丰度和F/B比在所有褪黑激素治疗组中显示出改善，这也是本研究的重点。一起来看,我们的研究首次报道了由于光周期变化诱导的CD和高脂肪高热量饮食诱导的生活方式障碍导致的肠道微生物群扰动.Further,褪黑激素介导的肠道微生物组恢复活力提供了其在改善肠道菌群失调中的作用的初步证据，需要详细审查。
