scholarly journals Gut Microbiota Mediates Oolong Tea Polyphenols Alleviation of Circadian Rhythm Disturbance

Author(s):  
Ruonan Yan ◽  
Chi-Tang Ho ◽  
Yanan Liu ◽  
Ruilin Zhang ◽  
Zufang Wu ◽  
...  

Abstract BackgroundTea polyphenols can be digested in the intestinal tract so as to promote the growth of helpful gut microbiota, and through the production of catechin, tryptophan, acetic acid and other active substances which involved in the modulation of circadian rhythms mechanism to improve the circadian rhythm disorders and neurological weakness, while its specific mechanism is still unclear. The interaction between host circadian rhythm and gut microbes through the gut-brain axis (GBA) provides new clues for tea polyphenols to improve host health. Our present research mainly investigated the metabolites of the gut microbiota and the heterogeneous expression of circadian rhythm genes in the liver and hypothalamic, and then revealed the modulatory role of oolong tea polyphenols (OTP) of circadian rhythm disorder via the GBA. We used 16S rDNA and untargeted metabolomics sequencing techniques to analyze the effects of OTP on intestinal flora diversity and abundance of specific flora in mice with diurnal disorders, and to screen out marker metabolites which may be involved in circadian rhythm regulation. Transcriptomics and 10X single-cell sequencing were used to evaluate the effects of OTP on circadian rhythm genes in liver and hypothalamus and hypothalamus cell types in mice with diurnal disorders. The Y maze and Morris water maze experiments were investigated the effects of OTP on long-term and short-term memory impairment.ResultsBy establishing a circadian rhythm disorder mouse model, our experimental results showed that OTP improved the structural disorder of the intestinal microbiota caused by continuous darkness, especially significantly decreased the ratio of Firmicutes/Bacteroidetes (F/B), thereby modulating the production of metabolites related to pyruvate metabolism, glycolysis/gluconeogenesis, and tryptophan metabolism to alleviate the steady-state imbalance caused by circadian rhythm disorders. In addition, OTP can significantly ameliorate the rhythm oscillation disorder of specific gut microbes and liver clock genes induced by continuous darkness, and made dysrhythmic mice perform well in cognitive behavior tests. Simultaneously, OTP intervention increased the number of rhythmic expression genes in the liver which in the CD group has 156, while in the OTP group has 208. Transplanting fecal microbiota from the OTP group into germ-free mice exhibited that OTP significantly increased the number of hypothalamus cell clusters, up-regulated the number of astrocytes and fibroblasts, and enhanced the expression of circadian rhythm genes Cry2, Per3, Bhlhe41, Nr1d1, Nr1d2, Dbp, and Rorb in hypothalamic cells. ConclusionsOur results confirmed that OTP reduced the F/B ratio, made the daily oscillation of the intestinal microbiota tended to be regular, actively improve the intestinal microecological status, the content of important metabolite closely associated with circadian rhythm such as Tryptophan, Glutamine, 2-indolecarboxylic acid and some others has been significantly increased, the poor expression of clock genes (such as Cry2, Per3, Bhlhe41, Nr1d1, Nr1d2, Dbp and Rorb) in liver and hypothalamus cells has been improved. These results indicated that OTP can significantly improve the metabolic imbalance and cognitive impairment caused by the circadian rhythm disorder, maintain the host's homeostasis, which with potential prebiotic functional characteristics to positively contribute to host health.

2019 ◽  
Vol 67 (32) ◽  
pp. 8847-8854 ◽  
Author(s):  
Tongtong Guo ◽  
Dan Song ◽  
Chi-Tang Ho ◽  
Xin Zhang ◽  
Chundan Zhang ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kazuhito Tsuzuki ◽  
Yuuki Shimizu ◽  
Zhongyue Pu ◽  
Junya Suzuki ◽  
Shukuro Yamaguchi ◽  
...  

Introduction: Circadian rhythm disorder seen in shift-worker or jet-lag is major social health concerns in advanced industrialized countries. The aim of this study was to examine if circadian rhythm disorders would influence on angiogenesis and blood perfusion recovery in a mouse model of hind limb ischemia (HLI). Methods and Results: First, we established a jet-lag model in C57BL/6J (wild type; WT) mice (8-10 weeks old, N=10 for each) using a light controlled isolation box. Mice were exposed to advanced 8-hr light phase once every 4 days in a jet-lag group as previously described. Conversely, control mice were kept a regular condition of LD 12:12 (12-hr light and 12-hr dark). Then, we surgically induced HLI in each group. The results showed that the condition jet-lag deteriorated capillary formation detected by CD31-immunohistochemistry at post-operative day (POD) 28 and tissue blood perfusion recovery demonstrated by laser Doppler perfusion imaging (LDPI) in HLI. The expression of clock genes (i.e. Clock, Bmal1, Per2, Cry1 and 2 ) in ischemic muscles were regulated by jet-lag condition at POD7.Next, we examined whether inhibition of clock gene had any effects on angiogenesis. For this study, we focused on Cryptochrome ( Cry ), which is well known as one of the core-loop forming clock genes producing circadian rhythm in mammals. Our loss-of-function study revealed that the abilities of proliferation, migration and tube formation were significantly inhibited by CRY1 and CRY2 double knockdown in HUVECs. Interestingly, although the knockdown of CRY1 and CRY2 changed the mRNA expression of PERIOD2 , it did not affect those of BMAL1 and CLOCK in HUVECs. Finally, we tested if Cry1 and Cry2 double knockout ( Cry1/2 -DKO) mice of HLI models displayed worse blood perfusion recoveries with deterioration of angiogenesis. Cry1/2 -DKO mice were reported to display circadian rhythm disorder in previous reports. As results, compared with control WT mice, Cry1/2 -DKO mice revealed suppressed capillary density and tissue blood perfusion recovery in HLI model. Conclusion: Our data suggest that a maintenance of circadian rhythm plays an important role in reparative angiogenesis of the tissue ischemia model.


2020 ◽  
Vol 18 ◽  
pp. 205873922092915
Author(s):  
Dezhan Li ◽  
Wei Huang ◽  
Fang Yang ◽  
Bin Li ◽  
Shanshan Cai

Hypoxic–ischemic encephalopathy (HIE) in neonates can lead to severe chronic neurological deficit, including mental retardation, epilepsy, and sleep–wake cycle (SWC) disorder. Among these defects, little is known about the molecular mechanism of circadian rhythm disorder after HIE. Therefore, further study of sleep problems and its mechanism in HIE children will provide new ideas for clinical treatment of HIE children. For pediatric patients with cerebral ischemia, somnipathy often occurs due to visual and airway abnormalities. From May 2010 to August 2013, 128 newborns with history of HIE were followed up. Meanwhile, 88 normal full-term newborns in the same period were taken as the control group. The clinical data of the patients were collected and the sleep status was assessed by questionnaire. To establish the hypoxic–ischemic brain injury model of neonatal rats and analyze the mechanism of mir-182 in the circadian rhythm disorder caused by pineal function injury. The core clock genes during the regulation of the circadian clock were explored by bioinformatics methods. Patients’ sleep quality was affected by the circadian rhythm and respiratory problems; the pineal gland can regulate the core clock genes in the circadian clock during regulation. miR-182 was highly expressed in the pineal gland after hypoxic–ischemic brain damage (HIBD). Children with mild and moderate HIE showed significant sleep disorders in varying degrees, which provided a clinical basis for improving the long-term prognosis of children with HIE through targeted treatment of sleep disorders. MiR-182 is highly expressed in the pineal gland and is related to the expression of CLOCK protein. CLOCK gene is the target gene of miR-182, which provides a new target for the treatment of rhythm disorder related to the damage of pineal function caused by HIBD.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Liyuan Zhou ◽  
Lin Kang ◽  
Xinhua Xiao ◽  
Lijing Jia ◽  
Qian Zhang ◽  
...  

The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the “metabolic memory” and the Developmental Origins of Health and Disease (DOHaD) hypothesis. The mechanism of “metabolic memory” has become a hot topic in the field of DM worldwide and could be a key to understanding the pathogenesis of DM. In recent years, several large cohort studies have shown that shift workers have a higher risk of developing type 2 diabetes mellitus (T2DM) and worse control of blood glucose levels. Furthermore, a maternal high-fat diet could lead to metabolic disorders and abnormal expression of clock genes and clock-controlled genes in offspring. Thus, disorders of circadian rhythm might play a pivotal role in glucose metabolic disturbances, especially in terms of early adverse nutritional environments and the development of metabolic diseases in later life. In addition, as a peripheral clock, the gut microbiota has its own circadian rhythm that fluctuates with periodic feeding and has been widely recognized for its significant role in metabolism. In light of the important roles of the gut microbiota and circadian clock in metabolic health and their interconnected regulatory relationship, we propose that the “gut microbiota-circadian clock axis” might be a novel and crucial mechanism to decipher “metabolic memory.” The “gut microbiota-circadian clock axis” is expected to facilitate the future development of a novel target for the prevention and intervention of diabetes during the early stage of life.


2019 ◽  
Vol 37 (3) ◽  
pp. 579-599
Author(s):  
Melanie Pogach ◽  
Robert Joseph Thomas

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Carlos Magno da Costa Maranduba ◽  
Sandra Bertelli Ribeiro De Castro ◽  
Gustavo Torres de Souza ◽  
Cristiano Rossato ◽  
Francisco Carlos da Guia ◽  
...  

Many immune-based intestinal disorders, such as ulcerative colitis and Crohn’s disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work—gut microbiota, immune system, and their influence in the neuroimmune system.


2020 ◽  
Vol 1 (4) ◽  
pp. 1-6
Author(s):  
Abram Estafanous ◽  
Karim Sedky

Delayed sleep phase syndrome (DSPS) is a circadian rhythm disorder where individuals experience difficulty modifying the time they go to sleep and wake up in response to environmental changes. The circadian rhythm itself is regulated by a variety of clock genes, and various other genes (e.g., AA-NAT gene, CKIϵ gene) code for proteins that regulate clock genes. Various polymorphisms of the clock gene influencers have been shown to increase susceptibility to DSPS. This paper seeks to examine how certain cultural characteristics (e.g., napping, timing of meals, exposure to artificial light) and the presence of the AA-NAT gene (G619A polymorphism) and the CKIϵ gene (S408N polymorphism) influence the prevalence of DSPS amongst Japanese and Brazilian populations.


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