Biology subjects

Tan, B.

Publications and source records attributed to Tan, B..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Design of SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model

The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. In this study, we designed and synthesized 85 noncovalent PLpro inhibitors that bind to the newly discovered Val70Ub site and the known BL2 groove pocket. Potent compounds inhibited PLpro with inhibitory constant Ki values from 13.2 to 88.2 nM. The co-crystal structures of PLpro with eight leads revealed their interaction modes. The in vivo lead Jun12682 inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50 from 0.44 to 2.02 {micro}M. Oral treatment with Jun12682 significantly improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting PLpro inhibitors are promising oral SARS-CoV-2 antiviral candidates. One-Sentence SummaryStructure-guided design of SARS-CoV-2 PLpro inhibitors with in vivo antiviral efficacy in a mouse model.

microbiology↗

bioRxiv2023

Machine learning-based exploration, expansion and definition of the atropopeptide family of ribosomally synthesized and posttranslationally modified peptides

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) constitute a diverse class of natural products. Atropopeptides are a recent addition to the fast-growing number of RiPP families. Characterized members of the peptide family feature a particular intricate three-dimensional shape. Here we developed AtropoFinder, a machine learning-based algorithm to chart the biosynthetic landscape of the atropopeptides. AtropoFinder identified more than 650 atropopeptide biosynthetic gene clusters (BGCs). Through bioinformatics and modeling analyses, we pinpointed crucial motifs and residues in leader and core peptide sequences, prompting a refined definition of the atropopeptide RiPP family. Our study revealed that a substantial subset of atropopeptide BGCs harbors multiple tailoring genes, thus suggesting a broader structural diversity than previously anticipated. To verify AtropoFinder, we heterologously expressed four atropopeptide BGCs, which resulted in the identification of novel atropopeptides with varying peptide lengths, number and type of modifications. Most notably, our study resulted in the characterization of an atropopeptide that is more extensively modified than previously identified members, resulting in an even more rigid 3-dimensional shape. Moreover, one characterized atropopeptide BGC encoding a single P450 is involved in the biosynthesis of two peptides with the same sequence but distinct and non-overlapping modification patterns. This work expands the atropopeptide chemical space, advances our understanding of atropopeptide biosynthesis and underscores the potential of machine learning in uncovering the uncharted biosynthetic diversity encoded in RiPP biosynthetic blueprints.

bioinformatics↗

bioRxiv2023

Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Addiction prioritizes drug use over innate needs by "hijacking" brain circuits that direct motivation, but how this develops remains unclear. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we find that drugs of abuse augment ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell-type-specific manner. Combining "FOS-Seq", CRISPR-perturbations, and snRNA-seq, we identify Rheb as a shared molecular substrate that regulates cell-type-specific signal transductions in NAc while enabling drugs to suppress natural reward responses. Retrograde circuit mapping pinpoints orbitofrontal cortex which, upon activation, mirrors drug effects on innate needs. These findings deconstruct the dynamic, molecular, and circuit basis of a common reward circuit, wherein drug value is scaled to promote drug-seeking over other, normative goals.

neuroscience↗

bioRxiv2023

Cellular and Molecular Basis of Leptin Resistance

Obese humans and diet induced obese mice (DIO) have high leptin levels and fail to respond to the exogenous hormone suggesting that obesity is caused by leptin resistance, the pathogenesis of which is unknown. We found that leptin treatment reduced plasma levels of mTOR ligands leading us to hypothesize that mTOR activation might inhibit leptin signaling. Rapamycin, an mTOR inhibitor, reduced fat mass and increased leptin sensitivity in DIO mice but not in mice with defects in leptin signaling. Rapamycin restored leptins actions on POMC neurons but failed to reduce the weight of mice with defects in melanocortin signaling. mTOR activation in POMC neurons caused leptin resistance while POMC specific mutations in mTOR activators decreased the weight gain of DIO mice. Thus increased mTOR activity in POMC neurons is necessary and sufficient for the development of leptin resistance in DIO mice establishing a key pathogenic mechanism leading to obesity.

neuroscience↗

bioRxiv2023

A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT- based biosensing and biocomputing systems with genetically controllable and modular design elements.

bioengineering↗

bioRxiv2023

Automated, unbiased optoretinography reveals comprehensive nanoscopic dynamics of the outer retina in rodents

Phototransduction involves changes in concentration of ions and other solutes within photoreceptors and in subretinal space, which affect osmotic pressure and the associated water flow. Corresponding expansion and contraction of cellular layers can be imaged using optoretinography (ORG), based on phase-resolved optical coherence tomography (OCT). Until now, ORG could reliably detect only photoisomerization and phototransduction in photoreceptors, primarily in cones under very bright stimuli. By employing a novel subpixel bulk motion correction algorithm, which enabled imaging of the nanometer-scale tissue dynamics during minute-long recordings, and unsupervised learning of spatiotemporal patterns, we discovered optical signatures of the other retinal structures response to visual stimuli. These include inner and outer segments of rod photoreceptors, retinal pigment epithelium, and subretinal space in general. High sensitivity of our technique enabled detection of the retinal responses to very dim stimuli: down to 0.01% bleach level, corresponding to natural levels of scotopic illumination. We also demonstrated that with a single flash, the optoretinogram can map retinal responses across a 12{degrees}field of view, potentially replacing multifocal electroretinography, with its long acquisition time and low spatial resolution. This new technique expands the diagnostic capabilities and practical applicability of optoretinography, providing a more complete replacement of electroretinography, while combining structural and functional retinal imaging in the same OCT machine.

bioengineering↗

bioRxiv2022

Epigenetically silencing gluconeogenic enzyme PCK1 by EZH2 promotes renal tubulointerstitial fibrosis

Renal fibrosis is the common pathological pathway of various chronic kidney diseases (CKD) in progression to the end stage of renal failure. Impaired renal gluconeogenesis has been recently identified as a hallmark of CKD. The role of gluconeogenesis in renal fibrosis is currently unknown. Through RNA sequencing and cleavage under targets and tagmentation (CUT&Tag) sequencing analysis, we found that the phosphoenolpyruvate carboxykinase 1 (PCK1), a critical enzyme in gluconeogenesis, is negatively regulated by the methyltransferase enhancer of zeste homolog 2 (EZH2) in fibrotic kidneys, which was further confirmed by quantitative PCR, CUT&Tag and Western blotting analysis in unilateral ureteral obstruction (UUO) kidneys and renal cells. We further showed that pharmaceutical inhibition or conditional knockout of EZH2 increased PCK1 expression and attenuated renal fibrosis in two other mouse models. Moreover, the concentration of lactate, a glucogenic metabolic intermediate, was increased in mouse fibrotic kidneys, which was reduced by EZH2 inhibition. We further showed that glucose production was impaired in folic acid induced nephrotic mice and restored by EZH2 inhibition as assessed by pyruvate tolerance test. Importantly, the direct anti-gluconeogenesis effect of EZH2 on renal proximal epithelial cells was shown in human HK2 cells by analysis of gluconeogenic gene expression and production of glucose or lactate. Finally, inhibition of PCK1 by 3-mercaptopropionic acid abrogated the anti-fibrotic effect of EZH2 inhibitor in UUO kidneys. We conclude that EZH2 promotes renal tubulointerstitial fibrosis through epigenetic inhibition of PCK1. Our study suggests that therapeutic restoration of the impaired renal gluconeogenesis is beneficial to CKD patients. Translational StatementRenal fibrosis is the common pathological pathway of various chronic kidney diseases (CKD) in progression to the end stage of renal failure. Impaired renal gluconeogenesis has been recently identified as a hallmark of CKD. In this study, we found that the methyltransferase EZH2 is negatively correlated with the expression of the gluconeogenic enzyme PCK1 in fibrotic kidneys. Epigenetic inhibition of PCK1 by EZH2 promotes renal tubulointerstitial fibrosis. Our study indicates that renal gluconeogenesis in CKD can be epigenetically regulated and therapeutically targeted. Epigenetic restoration of renal gluconeogenesis is a potential therapeutic strategy to treat CKD patients with tubulointerstitial fibrosis.

molecular biology↗

bioRxiv2022

Shot-noise limited phase-sensitive imaging of moving samples by phase-restoring subpixel motion correction in Fourier-domain optical coherence tomography

Phase-sensitive Fourier-domain optical coherence tomography (FD-OCT) enables in-vivo, label- free imaging of cellular movements with detection sensitivity down to the nanometer scale, and it is widely employed in emerging functional imaging modalities, such as optoretinography (ORG), Doppler OCT, and optical coherence elastography. However, when imaging tissue dynamics in vivo, tissue movement or bulk motion introduces decorrelation noise that compromises motion detection performance, particularly in terms of sensitivity and accuracy. Here, we demonstrate that the motion-related decorrelation noise in FD-OCT can be accurately corrected by restoring the initial sampling points using our proposed Phase-Restoring Subpixel Image Registration (PRESIR) method. Derived from a general FD-OCT model, the PRESIR method enables translational shifting of complex-valued OCT images over arbitrary displacements with subpixel precision, while accurately restoring phase components. Unlike conventional approaches that shift OCT images either in the spatial domain at the pixel level or in the spatial frequency domain for subpixel correction, our method reconstructs OCT images by correcting axial displacement in the spectral domain (k domain) and lateral displacement in the spatial frequency domain. We validated the PRESIR method through simulations, phantom experiments, and in-vivo optoretinography in both rodents and human subjects. Our approach significantly reduced decorrelation noise during the imaging of moving samples, achieving phase sensitivity close to the fundamental limit determined by the signal-to-noise ratio (SNR).

bioengineering↗

bioRxiv2022

Distribution of Critical Areas for Ecological Conservation in Multiple Scenarios ---- Emphasizing the Impact of Human Activities

Determining critical ecological protected areas at the city (county) spatial scale is crucial for coordinating regional ecological environment management, control, and governance. It is a recognized consensus in academia that human activities significantly impact natural ecosystems. Many scholars ignore this point in the research process and only use several factors to characterize human influence. Therefore, this study takes Aksu City and Wensu County, important cities and towns in southern Xinjiang, as examples, focusing on the impact of human activities on the distribution of critical ecological protection areas. First, we simulated the range, intensity, and local natural conditions of human activities in the study area using geospatial data. We created corresponding resistance surfaces (human activity resistance surface and natural landscape resistance surface). We then assign different weights to the two resistance surfaces based on several possible scenarios, resulting in different synthetic resistance surfaces. Finally, we used the Linkage Mapper plugin to identify critical ecological reserves and compared several results. The results show that: Human activities have greatly interfered with the migration and dispersal of species, affecting the distribution of critical ecological reserves. The specific performance is that in the urban center area with high intensity of human activities, the number and location of the surrounding ecological corridors change significantly with the increase in the proportion of human activity resistance and the total area remains unchanged; As part of the ecological corridors, the ecological pinch points changes with the location of the corridor, and the whole area remains unchanged; The threshold range of the restoration value of ecological barrier points is reduced. The maximum value generated by the restoration of ecological barrier points is reduced, which shows that the restoration value of ecological barrier points decreases with increased human activities.

ecology↗

bioRxiv2021

The connection between Rap1 and Talin1 in CD4+ T Lymphocytes

Agonist induced increase in integrin affinity for ligands (activation) plays a pivotal role in T cell trafficking and functions. Activation requires Rap1 GTPase-mediated recruitment of talin1 to the integrins in the plasma membrane. Rap1-interacting adaptor molecule (RIAM) is a Rap1 effector that serves this function in T cells. In addition, Rap1 directly binds to talin1 to enable integrin activation in platelets. Here, we assessed the relative contributions of the Rap1-talin1 interaction and RIAM and provide a complete accounting of the connections between Rap1 and talin1 that support integrin activation in conventional CD4+ (Tconv) and CD25HiFoxp3+CD4+ regulatory T (Treg) cells. Disruption of both Rap1 binding sites in talin1 (talin1 (R35E,R118E)) causes a partial defect in L{beta}2, 4{beta}1 and 4{beta}7 integrin activation in both Tconv and Treg cells with resulting defects in T cell homing and functions. Over-expression of RIAM bypasses the integrin activation defect in Tconv cells expressing talin1 (R35E,R118E), indicating that RIAM can substitute for Rap1 binding to talin in integrin activation. Conversely, deletion of RIAM in talin1 (R35E,R118E) Tconv cells abrogates activation of L{beta}2, 4{beta}1 and 4{beta}7. RIAM and lamellipodin (LPD) are mammalian members of the MRL protein family; LPD plays a more important role than RIAM in Treg cell integrin activation. Nevertheless, loss of RIAM profoundly exacerbates the defects in Treg cell function caused by the talin1 (R35E,R118E) mutation. Most importantly, deleting both MRL proteins combined with talin1 (R35E,R118E) phenocopies the complete lack of integrin activation observed in Rap1a/b null Treg cells. In sum, these data reveal the functionally significant connections between Rap1 and talin1 that enable L{beta}2, 4{beta}1 and 4{beta}7 integrin activation in T cells.

cell biology↗

bioRxiv2021

Retrospective analysis of enhancer activity and transcriptome history

Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. Here, we utilize an inducible DCM-RNA-polymerase-subunit-b fusion protein, to label active genes and enhancers with a bacterial methylation mark that does not affect gene transcription and is propagated in S-phase. We applied this DCM-time-machine (DCM-TM) technology to study intestinal homeostasis, following enterocyte differentiation back in time, revealing rapid and simultaneous activation of enhancers and nearby genes during intestinal stem cell (ISC) differentiation. We provide new insights in the absorptive-secretory lineage decision in ISC differentiation, and show that ISCs retain a unique chromatin landscape required to maintain ISC identity and delineate future expression of differentiation associated genes. DCM-TM has wide applicability in tracking cell states, providing new insights in the regulatory networks underlying cell state changes in development and differentiation.

developmental biology↗

bioRxiv2021

Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Methods: 513 participants with Alzheimers Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinsons Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH. Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.

neuroscience↗

bioRxiv2021

CNAHap: a germline haplotyping method using tumor allele-specific copy number alteration

Haplotype phasing is indispensable to study human genetics. The pervasiveness of large copy number variant segments in solid tumors brings possibilities to resolve long germline phasing blocks utilizing allele imbalance in tumor data. Although there exist such studies, none of them provide easy-use software based on availability and usability. Herein, we present a novel tool, CNAHap, to determine the allele-specific copy number in tumor and then phase germline variants according to the imbalanced alleles in tumor genomes. We also provide interactive web interfaces to visualize the copy number and phase landscape from CNAHap. On in silico datasets, CNAHap demonstrates higher allele-specific copy number calling accuracy than the benchmark tool and generates long phasing blocks. As a case study on Hepatocellular carcinoma, CNAHap successfully generates huge phase blocks with the averages of N50 and N90 as 25M and 7M, respectively, and finds the Olfactory receptor family is recurrent amplified. Our results illustrate the efficacy of CNAHap in determining tumor allele-specific copy numbers and their long germline haplotypes. CNAHap is available at https://github.com/bowentan/CNAHap and the CNAHap visualization web interfaces are hosted at bio.oviz.org.

bioinformatics↗

bioRxiv2021

Genetic and epigenetic determinants of reactivation of Mecp2 and the inactive X chromosome in neural stem cells.

Rett Syndrome is a neurodevelopmental disorder in girls that is caused by heterozygous inactivation of the chromatin remodeler gene MECP2. Rett Syndrome may therefore be treated by reactivation of the wild type copy of MECP2 from the inactive X chromosome. Most studies that model Mecp2 reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model system for monitoring Mecp2 reactivation that is more sensitive and versatile than any bioluminescent and fluorescent system currently available. The model consists of neural stem cells derived from female mice with a dual reporter system where MECP2 is fused to NanoLuciferase and TdTomato on the inactive X chromosome. We show by bioluminescence and fluorescence that Mecp2 is synergistically reactivated by 5-Aza treatment and Xist knockdown. As expected, other genes on the inactive X chromosome are also reactivated, the majority of which overlaps with genes reactivated early during reprogramming of mouse embryonic fibroblasts to iPSCs. Genetic and epigenetic features such as CpG density, SINE elements, distance to escapees and CTCF binding are consistent indicators of reactivation, whereas different higher order chromatin areas are either particularly prone or resistant to reactivation. Our MeCP2 reactivation monitoring system thereby suggests that genetic and epigenetic features on the inactive X chromosome affect reactivation of its genes, irrespective of cell type or procedure of reactivation.

molecular biology↗

bioRxiv2020

Remdesivir inhibits renal fibrosis in obstructed kidneys

AimKidney impairment is observed in patients with COVID-19. We aimed to demonstrate the effect of anti-COVID-19 agent remdesivir on renal fibrosis. MethodsRemdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-{beta} stimulated renal fibroblasts (NRK-49F) and human renal epithelial cells (HK2). Cell viability was determined by CCK8 assay, and fibrotic markers were measured by Western blotting. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Massons trichrome staining and Western blotting. ResultsRemdesivir and GS-441524 inhibited cell proliferation and the expression of fibrotic markers (fibronectin, pSmad3, and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis of UUO kidneys. Renal and liver function were not changed in remdesivir treated UUO mice. Remdesivir can not be detected, but two remdesivir metabolites were detected after injection. ConclusionRemdesivir inhibits renal fibrosis in obstructed kidneys.

pharmacology and toxicology↗

bioRxiv2019

SpecHap: a fast haplotyping method based on spectral graph theory

Haplotype phasing is essential to study diploid eukaryotic organisms. High-throughput sequencing, including next-generation sequencing and third-generation sequencing from different technologies, brings possibilities for haplotype assembly. Although there exist multiple haplotype phasing algorithms, only a few are portable across sequencing technologies with the premise of efficiency and accuracy. Herein, we proposed SpecHap, a novel haplotype assembly tool that leverages spectral graph theory, transforming haplotype phasing into an algebraic problem. On both in silico and whole-genome-sequencing datasets, SpecHap consumed less memory and required less CPU time, yet achieved comparable accuracy comparing to state-of-art methods across all the test instances of next-generation sequencing, linked-reads, high-throughput chromosome conformation capture sequencing, PacBio single-molecule real-time sequencing and Oxford Nanopore long-reads sequencing data. Furthermore, SpecHap successfully phased an individual Ambystoma mexicanumm, a species with gigantic diploid genomes, within 6 CPU hours and 945MB peak memory usage, while other tools failed to yield results either due to a memory overflow (40GB) or a time limit excess (5 days). Our results demonstrated that SpecHap is scalable, efficient and accurate for diploid phasing, supporting diverse sequencing platforms.

bioinformatics↗

bioRxiv2019

Integrating genome-wide association mapping of additive and dominance genetic effects to improve genomic prediction accuracy in Eucalyptus

Genome-wide association studies (GWAS) is a powerful and widely used approach to decipher the genetic control of complex traits. A major challenge for dissecting quantitative traits in forest trees is statistical power. In this study, we use a population consisting of 1123 samples from two successive generations that have been phenotyped for growth and wood property traits and genotyped using the EuChip60K chip, yielding 37,832 informative SNPs. We use multi-locus GWAS models to assess both additive and dominance effects to identify markers associated with growth and wood property traits in the eucalypt hybrids. Additive and dominance association models identified 78 and 82 significant SNPs across all traits, respectively, which captured between 39 and 86% of the genomic-based heritability. We also used SNPs identified from the GWAS and SNPs using less stringent significance thresholds to evaluate predictive abilities in a genomic selection framework. Genomic selection models based on the top 1% SNPs captured a substantially greater proportion of the genetic variance of traits compared to when all SNPs were used for model training. The prediction ability of estimated breeding values was significantly improved for all traits using either the top 1% SNPs or SNPs identified using a relaxed p-value threshold (p<10-3). This study highlights the added value of also considering dominance effects for identifying genomic regions controlling growth traits in trees. Moreover, integrating GWAS results into genomic selection method provides enhanced power relative to discrete associations for identifying genomic variation potentially useful in tree breeding.

genetics↗

bioRxiv2019

Admistration of Exogenous Melatonin Improves the Diurnal Rhythms of Gut Microbiota in High Fat Diet-Fed Mice

Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of admistartion of exogenous melatonin on the diurnal variation in gut microbiota in high fat diet (HFD)-fed mice is obscure. Here, we further confirmed the anti-obesogenic effect of melatonin on in mice feed with HFD for two weeks. Samples were collected every 4 h within a 24-h period and diurnal rhythms of clock genes expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm only in the control and melatonin treated mice, but not in the HFD-fed mice. Rhythmicity of these parameters were similar between control and melatonin treated HFD mice compared with the HFD group, indicating an improvement of melatonin in the diurnal clock of host metabolism in HFD-fed mice. 16S rDNA sequencing showed that most microbiota exhibited a daily rhythmicity and the trends differentiated at different groups and different time points. We also identified several specific microbiota correlating with the circadian clock genes and serum lipid indexes, which might contribute the potential mechanism of melatonin in HFD-fed mice. Interestingly, administration of exogenous melatonin only at daytime exhibited higher resistance to HFD-induced lipid dysmetabolism than nighttime treatment companying with altered gut microbiota (Lactobacillus, Intestinimonas, and Oscillibacter). Importantly, the responses of microbiota transplanted mice to HFD feeding also varied at different transplanting times (8:00 and 16:00) and different microbiota donors. In summary, daily oscillations in the expression of circadian clock genes, serum lipid indexes, and gut microbiota, appears to be driven by a short-time feeding of an HFD. Administration of exogenous melatonin improved the compositions and diurnal rhythmicity of gut microbiota, which might be linked to host diurnal rhythm and metabolism.\n\nImportancePrevious studies show that a circadian hormone, melatonin, involves in host lipid metabolism by reprogramming gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of melatonin drinking on the diurnal variation in gut microbiota in high fat diet-fed mice is obscure. Here, we found that 24-h oscillations were widely occurred in circadian clock genes, serum lipid indexes, and gut microbiota. Melatonin drinking improved the compositions and circadian rhythmicity of gut microbiota, which might be linked to host circadian rhythm and metabolism.

microbiology↗