Biology subjects

Zhang, Q.

Publications and source records attributed to Zhang, Q..

At least 541 records · Page 30Linked to original sources

bioRxiv2021

High performance of a GPU-accelerated variant calling tool in genome data analysis

Rapid advances in next-generation sequencing (NGS) have facilitated ultralarge population and cohort studies that utilized whole-genome sequencing (WGS) to identify DNA variants that may impact gene function. Massive sequencing data require highly efficient bioinformatics tools to complete read alignment and variant calling as the fundamental analysis. Multiple software and hardware acceleration strategies have been developed to boost the analysis speed. This study comprehensively evaluated the germline variant calling of a GPU-based acceleration tool, BaseNumber, using WGS datasets from several sources, including gold-standard samples from the Genome in a Bottle (GIAB) project and the Golden Standard of China Genome (GSCG) project, resequenced GSCG samples, and 100 in-house samples from the China Deafness Genetics Consortium (CDGC) project. Sequencing data were analyzed on the GPU server using BaseNumber, the variant calling outputs of which were compared to the reference VCF or the results generated by the Burrows-Wheeler Aligner (BWA) + Genome Analysis Toolkit (GATK) pipeline on a generic CPU server. BaseNumber demonstrated high precision (99.32%) and recall (99.86%) rates in variant calls compared to the standard reference. The variant calling outputs of the BaseNumber and GATK pipelines were very similar, with a mean F1 of 99.69%. Additionally, BaseNumber took only 23 minutes on average to analyze a 48X WGS sample, which was 215.33 times shorter than the GATK workflow. The GPU-based BaseNumber provides a highly accurate and ultrafast variant calling capability, significantly improving the WGS analysis efficiency and facilitating time-sensitive tests, such as clinical WGS genetic diagnosis, and sheds light on the GPU-based acceleration of other omics data analyses.

bioinformatics↗

bioRxiv2021

A Graph Convolutional Network-based screening strategy for rapid identification of SARS-CoV-2 cell-entry inhibitors

The cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time-consuming and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in [~]2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/471787v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1632bc4org.highwire.dtl.DTLVardef@1ce912borg.highwire.dtl.DTLVardef@9cdc86org.highwire.dtl.DTLVardef@521712_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma

Multiple myeloma (MM), characterized by high intratumour heterogeneity, accounts for [~]10% of all haematologic malignancies. Stratified by the Revised International Staging System (R-ISS), little is known about R-ISS-related plasma cell (PC) heterogeneity, gene expression modules in cytotoxic T/NK cells and immunoregulatory ligands and receptors. Herein, we constructed a single-cell transcriptome atlas of bone marrow in normal and R-ISS-staged MM patients. Focusing on PCs, we identified and validated a subset of GZMA+ cytotoxic PCs. In addition, a malignant PC population with high proliferation capability (proliferating PCs) was associated with unfavourable prognosis and EBV infection in our collected samples. Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), a specific marker of proliferating PCs, was shown to induce MM cell line proliferation and serve as a detrimental marker in MM. Subsequently, three R-ISS-dependent gene modules in cytotoxic CD8+ T and NKT cells were identified and functionally analysed. Finally, cell-cell communication between neutrophils and proliferating PCs with cytotoxic CD8+ T and NKT cells was investigated, which identified intercellular ligand receptors and potential immunotargets such as SIRPA-CD47 and TIGIT-NECTIN3. Collectively, this study provides an R-ISS-related single-cell MM atlas and reveals the clinical significance of two PC clusters, as well as potential immunotargets in MM progression.

cancer biology↗

bioRxiv2021

Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a promising "off-the-shelf" cell product for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryonic body-formation and feeder-based expansion steps, which bring instability, time-consuming, and high costs for manufacture. In this study, we develop an embryonic body-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time window of 27-day induction, millions of hPSC input can produce over billions of iNK cells without the necessity of NK cell-expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells by mechanisms of direct cytotoxity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

immunology↗

bioRxiv2021

Systems genetics uncovers microbe-lipid-host connections in the murine gut

The molecular bases of how host genetic variation impact gut microbiome remain largely unknown. Here, we used a genetically diverse mouse population and systems genetics strategies to identify interactions between molecular phenotypes, including microbial functions, intestinal transcripts and cecal lipids that influence microbe-host dynamics. Quantitative trait loci (QTL) analysis identified genomic regions associated with variations in bacterial taxa, bacterial functions, including motility, sporulation and lipopolysaccharide production, and levels of bacterial- and host-derived lipids. We found overlapping QTL for the abundance of Akkermansia muciniphila and cecal levels of ornithine lipids (OL). Follow-up studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that OL have immunomodulatory effects and identified intestinal transcripts co-regulated with these traits. Collectively, these results suggest that OL are key players in A. muciniphila-host interactions and support the role of host genetics as a determinant of responses to gut microbes.

genetics↗

bioRxiv2021

Adaptor linked K63 di-Ubiquitin activates Nedd4/Rsp5 E3 ligase

Nedd4/Rsp5 family E3 ligases mediate numerous cellular processes, many of which require the E3 ligase to interact with PY-motif containing adaptor proteins. Several Arrestin-Related Trafficking adaptors(ARTs) of Rsp5 were self-ubiquitinated for activation, but the regulation mechanism remains elusive. Remarkably, we demonstrate that Art1, Art4, and Art5 undergo K63-linked di-ubiquitination by Rsp5. This modification enhances the PM recruitment of Rsp5 by Art1 or Art5 upon substrate induction, required for cargo protein ubiquitination. In agreement with these observations, we find that di-ubiquitin strengthens the interaction between the Pombe orthologs of Rsp5 and Art1, Pub1 and Any1. Further, we discover that the HECT domain exosite protects the K63-linked di-ubiquitin on the adaptors from cleavage by the deubiquitination enzyme Ubp2. Strikingly, loss of this protection results in the loss of K63-linked di-ubiquitin from the adaptors and diverts the adaptors for K48-linked poly-ubiquitination and proteasome-mediated degradation. Together, our study uncovers a novel ubiquitination modification implemented by Rsp5 adaptor proteins, underscoring the regulatory mechanism of how adaptor proteins control the recruitment and activity of Rsp5 for the turnover of membrane proteins.

cell biology↗

bioRxiv2021

Using light-sheet microscopy to study spontaneous activity in the developing lateral-line system

Hair cells are the sensory receptors in the auditory and vestibular systems of all vertebrates, and in the lateral-line system of aquatic vertebrates. During development, spontaneous activity in hair cells shapes the formation of these sensory systems. In auditory hair cells of mice, coordinated waves of spontaneous activity can be triggered by concomitant activity in nearby supporting cells. But in mammals, developing auditory and vestibular hair cells can also autonomously generate spontaneous events independent of supporting cell activity. To date, significant progress has been made studying spontaneous activity in the auditory and vestibular systems of mammals, in isolated cultures. The purpose of this work is to explore the zebrafish lateral-line system as a model to study and understand spontaneous activity in vivo. Our work applies genetically encoded calcium indicators along with light-sheet fluorescence microscopy to visualize spontaneous calcium activity in the developing lateral-line system. Consistent with our previous work, we show that spontaneous calcium activity is present in developing lateral-line hair cells. We now show that supporting cells that surround hair cells, and cholinergic efferent terminals that directly contact hair cells are also spontaneously active. Using two-color functional imaging we demonstrate that spontaneous activity in hair cells does not correlate with activity in either supporting cells or cholinergic terminals. We find that during lateral-line development, hair cells autonomously generate spontaneous events. Using localized calcium indicators, we show that within hair cells, spontaneous calcium activity occurs in two distinct domains-the mechanosensory bundle and the presynapse. Further, spontaneous activity in the mechanosensory bundle ultimately drives spontaneous calcium influx at the presynapse. Comprehensively, our results indicate that in developing lateral-line hair cells, autonomously generated spontaneous activity originates with spontaneous mechanosensory events. Overall, with robust spontaneous activity three different cell types, the developing lateral line is a rich model to study these activities in an intact sensory organ. Future work studying this model may further our understanding of these activities and their role in sensory system formation, function and regeneration.

developmental biology↗

bioRxiv2021

Disassembly of hemidesmosomes promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin into focal adhesions

Loss of 6{beta}4-dependent hemidesmosomes has been observed during prostate cancer progression. However, the significance and underlying mechanisms by which aberrant hemidesmosome assembly may modulate tumorigenesis remain elusive. Using an extensive CRISPR/Cas9-mediated genetic engineering approaches in different prostate cancer cell lines combined with in vivo tumorigenesis studies in mice, bone marrow-on-chip assays and bioinformatics, as well as histological analysis of prostate cancer patient cohorts, we demonstrated that simultaneous loss of PTEN and hemidesmosomes induced several tumorigenic properties including proliferation, migration, resistance to anoikis, apoptosis, and drug treatment in vitro, and increased metastatic capacity in vivo. Our studies showed that these effects were driven by activation of EGFR/PI3K/Akt and FAK/Src-pathways and were abolished by plectin downregulation. Therefore, dual loss of PTEN and hemidesmosomes may have diagnostic value helping to stratify prostate cancer patients with high risk for development of aggressive disease and highlight plectin as a potential therapeutic target in prostate cancer.

cancer biology↗

bioRxiv2021

Base-resolution prediction of transcription factor binding signals by a deep learning framework

Transcription factors (TFs) play an important role in regulating gene expression, thus the identification of the sites bound by them has become a fundamental step for molecular and cellular biology. In this paper, we developed a deep learning framework leveraging existing fully convolutional neural networks (FCN) to predict TF-DNA binding signals at the base-resolution level, called FCNsignal. The proposed FCNsignal can simultaneously achieve the following tasks: (i) modeling the base-resolution signals of binding regions; (ii) discriminating binding or non-binding regions; (iii) locating TF-DNA binding regions; (iv) predicting binding motifs. The experimental results on 53 TF ChIP-seq datasets and 6 chromatin accessibility ATAC-seq datasets show that our proposed framework outperforms some existing state-of-the-art methods. In addition, we explored to use the trained FCNsignal to locate all potential TF-DNA binding regions on a whole chromosome and predict DNA sequences of arbitrary length, and the results show that our framework can find most of the known binding regions and accept sequences of arbitrary length. Furthermore, we demonstrated the potential ability of our framework in discovering causal disease-associated single-nucleotide polymorphisms (SNPs) through a series of experiments. Author summaryIdentification of transcription factor binding sites (TFBSs) is fundamental to study gene regulatory networks in biological systems, as TFs activate or suppress the transcription of genes by binding to specific TFBSs. With the development of high-throughput sequencing technologies and deep learning (DL), several DL-based approaches have been developed for systematically studying TFBSs, achieving impressive performance. Nevertheless, these methods either excessively focus on discriminating binding or non-binding sequences or individually accomplish multiple TFBSs-associated tasks. In this work, we provide an integrated framework, which utilizes the FCN architecture to predict TF-DNA binding signals at the base-resolution level, to simultaneously study multiple TFBSs-associated tasks. More importantly, we also demonstrate that our proposed framework has the ability to locate all potential TF-DNA binding regions from DNA sequences of arbitrary length. We hope that our framework can provide a new perspective on studying the mechanism of TF-DNA binding and its related tasks.

bioinformatics↗

bioRxiv2021

Dominant species determine ecosystem stability across scales in Inner Mongolian grassland

There is an urgent need to extend knowledge on ecosystem temporal stability to larger spatial scales because presently available local-scale studies generally do not provide effective guide for management and conservation decisions at the level of an entire region with diverse plant communities. We investigated temporal stability of plant biomass production across spatial scales and hierarchical levels of community organization and analyzed impacts of dominant species, species diversity and climatic factors using a multi-site survey of Inner Mongolian grassland. We found that temporal stability at a large spatial scale, i.e. a large area aggregating multiple local communities, was related to temporal stability of and asynchrony among spatially separated local communities and large-scale population dynamics of dominant species, yet not to species richness. Additionally, a lower mean and higher variation of yearly precipitation destabilized communities at local and large scales by destabilizing dominant species population dynamics. We argue that, for semi-arid temperate grassland, dynamics and precipitation responses of dominant species and asynchrony among local communities stabilize ecosystems at large spatial scales. Our results indicate that reduced amounts and increased variation of precipitation may present key threats to the sustainable provision of biological products and services to human well-being in this region.

ecology↗

bioRxiv2021

A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure

The COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.

biochemistry↗

bioRxiv2021

Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cells

The expression of transcription factor Hoxb5 specifically marks the functional hematopoietic stem cells (HSC) in mice. However, our recent work demonstrated that ectopic expression of Hoxb5 exerted little effect on HSC but could convert B cell progenitors into functional T cells in vivo. Thus, cell type- and development stage-specific roles of Hoxb5 in hematopoietic hierarchy await more extensive exploration. Here, with a mouse strain engineered with conditional expression of Hoxb5, we unveiled that induced expression of Hoxb5 in mouse multipotent progenitor cells (MPP) led to the generation of a de novo Sca1+cKit+Mac1+CD48+ (Mac1+CD48+SK) cell type, which has the ability to repopulate long-term multi-lineage hematopoiesis in serial transplant recipients. RNA-seq analyses showed that Mac1+CD48+SK cells exhibited an acquired machinery of DNA replication and cell division, which resembled nature fetal liver HSC cells (FL HSC). In short, our current study uncovers that Hoxb5 is able to empower MPP with self-renewal potential, thereby providing new strategies to reprogram blood progenitor cells into HSC-like cells.

cell biology↗

bioRxiv2021

Mitoxantrone modulates a glycosaminoglycan-spike complex to inhibit SARS-CoV-2 infection

Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA-approved topoisomerase inhibitor, targets a spike-GAG complex to compromise the fusogenic function of spike in viral entry. As a single agent, Mitoxantrone inhibits the infection of an authentic SARS-CoV-2 strain in a cell-based model and in human lung EpiAirway 3D tissues. Gene expression profiling supports the plasma membrane as a major target of Mitoxantrone but also underscores an undesired activity targeting nucleosome dynamics. We propose that Mitoxantrone analogs bearing similar GAG-binding activities but with reduced affinity for DNA topoisomerase may offer an alternative therapy to overcome breakthrough infections in the post-vaccine era.

cell biology↗

bioRxiv2021

iHypoxia: an integrative database of the expression dynamics of proteins in response to hypoxia in animals

Decreased oxygen concentrations (hypoxia) outside of the physiological range may severely subvert cell, tissue, and organism survival. Mammals have evolved mechanisms to sense hypoxia and induce a series of hypoxic responses. In recent years, high-throughput techniques have greatly promoted global perturbation studies of protein expression during hypoxia, and these studies have contributed to the understanding of the complex regulatory networks of hypoxia. In this study, we developed an integrated resource for the expression dynamics of proteins in response to hypoxia (iHypoxia), which contains 1,629 expression events of 1,215 proteins identified by low-throughput experiments (LTEs) and 154,953 quantitative expression events of 36,194 proteins identified by high-throughput experiments (HTEs) from five mammals that exhibit a response to hypoxia. Various experimental details such as the hypoxic experimental conditions, expression patterns, and samples were carefully collected and integrated. In addition, we conducted an orthologous search and identified 581,763 proteins that may respond to hypoxia among 50 animals. An enrichment analysis of human proteins identified from LTEs showed that these proteins were enriched in certain drug targets and cancer genes. The annotation of known posttranslational modification (PTM) sites to proteins identified by LTEs revealed that these proteins underwent extensive PTMs, particularly phosphorylation, ubiquitination and acetylation. Based on the results, iHypoxia provides a convenient and user-friendly method for users to obtain hypoxia-related information of interest. We anticipate that iHypoxia, which is freely accessible at http://ihypoxia.omicsbio.info, will advance the understanding of hypoxia and serve as a valuable data resource.

bioinformatics↗

bioRxiv2021

Realization of phosphorylation hypothesis of sleep by mammalian CaMKIIβ

The reduced sleep duration observed in Camk2a and Camk2b knockout mice revealed the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CAMKII{beta} as sleep-promoting kinases and lead to the phosphorylation hypothesis of sleep. However, the underlying mechanism of sleep regulation by kinases and protein phosphorylation is largely unknown. Here, we demonstrate that the phosphorylation states of CaMKII{beta} regulates sleep duration and sleep needs. Importantly, the activation or inhibition of CaMKII{beta} can increase or decrease sleep duration by almost two-fold, supporting the role of CaMKII{beta} as a core sleep regulator in mammals. This sleep regulation depends on the kinase activity of CaMKII{beta} in excitatory neurons. Furthermore, CaMKII{beta} mutants mimicking different phosphorylation states can regulate various sleep steps including sleep induction, sleep maintenance, and sleep cancelation. Key CaMKII{beta} residues responsible for the mode switch undergo ordered (auto-)phosphorylation. We thus propose that ordered multi-site phosphorylation of CaMKII{beta} underlies multi-step sleep regulation in mammals.

neuroscience↗

bioRxiv2021

A Phytochrome B-PIF4-MYC2 Module Tunes Secondary Cell Wall Thickening in Response to Shaded Lighting

Secondary cell walls (SCW) in stem xylem cells provide mechanical strength and structural support for growth. SCW thickening is light- regulated and varies under different light growth conditions. Our previous study revealed that blue light enhances SCW thickening through the activity of MYC2 directed by CRYPTOCHROME1 (CRY1) signaling in stem xylary fiber cells. In this study, we demonstrate that the low ratio of red: far-red light (R:FR) of the shaded light condition inhibits SCW thickening in the inflorescence stem of Arabidopsis. Phytochrome B (PHYB) plays a dominant role in perceiving the R:FR balance. Under white and red-light conditions, phyB mutants display thinner SCWs in xylary fibers, but thicker SCWs are deposited in the PHYTOCHROME INTERACTING FACTORS (PIFs) quadruple mutant pif1pif3pif4pif5 (pifq), suggesting involvement of the PHYB-PIFs signaling module in regulating SCW thickening. Interaction of PIF4 with MYC2 affects MYC2 localization in nuclei and inhibits its transactivation activity on the NST1 promoter. Shade conditions mediate the PIF4 interaction with MYC2 to regulate SCW thickening. Genetic analysis confirms that the regulation of SCW thickening by PIFs is dependent on MYC2 function. Together, these data reveal a molecular mechanism for the effect of shaded light inhibition on SCW thickening in stems of Arabidopsis.

plant biology↗

bioRxiv2021

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

microbiology↗

bioRxiv2021

The gut microbial signature of gestational diabetes mellitus and the association with diet intervention

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The link between microbiota and diet management contributes to metabolic homeostasis in GDM. Therefore, it is crucial to understand the structure of the gut microbiota in GDM and to explore the effect of dietary management on the microbiota structure. In this study, we analyzed the composition of the gut microbiota between 27 GDM and 30 healthy subjects at two time points using Illumina HiSeq 2500 platform. The taxonomy analyses suggested that the overall bacteria clustered by diabetes status, rather than diet intervention. Of particular interest, the phylum Acidobacteria in GDM was significantly increased, and positively correlated with blood glucose levels. Moreover, Partial least-squares discriminant analysis (PLS-DA) revealed that certain genera in the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Lentisphaerae characterized the GDM gut microbiota. Correlation analysis indicated that blood glucose levels and BMI index were correlated with the relative abundance of SCFAS-producing genera. Through the comparison between the GDM and healthy samples with or without diet intervention, we discovered that the role of short-term diet management in GDM processes is associated with the change in the Firmicutes/Bacteroidetes ratio and some specific taxa, rather than an alternative gut microbial pattern. Our study have important implications for understanding the beneficial effects of diet intervention on the specific gut microbiota and thus possibly their metabolism in pregnant women with GDM. ImportanceUnderstanding the composition and dynamics of the gut microbiota in GDM women under diet intervention is important because there may be opportunities for preventive strategies. We examined the relationships between GDM gut microbiota at two times before and after the diet intervention during second trimester of pregnancy and clinical characteristics in cohort of GDM women. We found that short-term diet management in GDM processes is associated with changes in the Firmicutes/Bacteroidetes ratio and some specific taxa rather than an alternative gut microbial pattern. Our study highlights the importance of considering diet intervention as the rescue of microbial dysfunction of GDM disease and can serve as a strategy for early prevention in future study.

microbiology↗