Biology subjects

He, Z.

Publications and source records attributed to He, Z..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

The Alfin-like transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via a peroxidase GmPRDX6

Soybean is a valuable oil crop cultivated throughout the world, but also highly susceptible to environmental stressors. The development of approaches to enhancing soybean stress resistance is thus vital to improving yields. In prior studies, Alfin has been shown to serve as an epigenetic regulator of plant growth and development. No studies of Alfin have yet been reported in soybean, however. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related transcription factor GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of the peroxidase GmPRDX6. Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to directly bind the GmPRDX6 promoter. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 can promote the upregulation of GmPRDX6, which subsequently localizes to the ER, reduced ROS levels, promotes ER homeostasis, and helps ensure the normal growth of soybean even under ER stress. This study highlights a novel genetic target for the future molecular breeding of stress-resistant soybean cultivars. HIGHLIGHTGmAlfin09 can increase the expression of GmPRDX6 to reduce ROS level under ER stress.

plant biology↗

bioRxiv2023

Comparison of the effects of PTH (1-34), PTHrP (1-36) and abaloparatide on the murine osteoblast transcriptome.

Teriparatide (PTH(1-34)) and its analogs, PTHrP(1-36) and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy over long-term use is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize that they may also differentially modulate the osteoblast transcriptome. We show that treatment of mouse calvarial osteoblasts with 1 nM of the 3 peptides for 4 h results in RNA-Seq data with PTH(1-34) regulating 367 genes, including 194 unique genes; PTHrP(1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed differences in Wnt signaling, cAMP-mediated signaling, bone mineralization, morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, cytokine receptor/binding activity and many other actions in molecular functions. The 3 peptides increased Vdr, Cited1 and Pde10a mRNAs in a pattern similar to Rankl, i.e., PTH(1-34) > ABL > PTHrP(1-36). mRNA abundance of other genes based on gene/pathway analyses, including Wnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epha3, Tcf7, Crem, Fzd5, Pp2r2a, and Dvl3 showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, siRNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH(1-34)-treated cells revealed that Vdr and Wnt4 genes are regulated by SIKs and CRTCs, while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to examine the global effects of these peptides on the osteoblast transcriptome. Further delineation of which signaling events are attributable to PTH(1-34), PTHrP(1-36) or ABL exclusively and which are shared among all 3 will help improve our understanding of the effects these peptides have on the osteoblast and lead to the refinement of PTH-derived treatments for osteoporosis.

physiology↗

bioRxiv2023

VHL Mutation Drives Human Clear Cell Renal Cell Carcinoma Progression Through PI3K/AKT-Dependent Cholesteryl Ester Accumulation

BackgroundCholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. MethodsEnabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. FindingsSurprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIF and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. InterpretationCollectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. FundingThis work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No.2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

cancer biology↗

bioRxiv2023

EFNB1 level affects drug response in DLBCL cell lines

Targeted therapy was a promising therapy for aggressive B-cell lymphoma. However, drug resistance was still an unavoidable problem. Here, we explored the effect of EFNB1 on drug response. Analysis of IC50 data showed that high level of EFNB1 was associated with resistance to most targeted drugs targeting BCR in human DLBCL cell lines. Drug response assay showed that Efnb1 could enhance SRC phosphorylation and increased the sensitivity of cells to SRC inhibitors. Meanwhile, Efnb1 could sensitize cells to most cytotoxic drugs, especially DOX and VCR. Efnb1 could confer cells sensitivity to VCR by enhancing the phosphorylation of Stmn1 at serine 28. Survival analysis revealed that the expression level of genes phosphorylated in Efnb1 cells were associated with poor prognosis of human DLBC. Together, this study revealed that EFNB1 level, as a non-genetic mechanism, greatly affected drug response of targeted drugs and cytotoxic drugs through the phosphorylation network. Our findings would provide important insights into EFNB1-SRC activated B-cell lymphoma and efficacy evaluation.

pharmacology and toxicology↗

bioRxiv2022

MIDAS: a deep generative model for mosaic integration and knowledge transfer of single-cell multimodal data

AO_SCPLOWBSTRACTC_SCPLOWRapidly developing single-cell multi-omics sequencing technologies generate increasingly large bodies of multimodal data. Integrating multimodal data from different sequencing technologies, i.e. mosaic data, permits larger-scale investigation with more modalities and can help to better reveal cellular heterogeneity. However, mosaic integration involves major challenges, particularly regarding modality alignment and batch effect removal. Here we present a deep probabilistic framework for the mosaic integration and knowledge transfer (MIDAS) of single-cell multimodal data. MIDAS simultaneously achieves dimensionality reduction, imputation, and batch correction of mosaic data by employing self-supervised modality alignment and information-theoretic latent disentanglement. We demonstrate its superiority to other methods and reliability by evaluating its performance in full trimodal integration and various mosaic tasks. We also constructed a single-cell trimodal atlas of human peripheral blood mononuclear cells (PBMCs), and tailored transfer learning and reciprocal reference mapping schemes to enable flexible and accurate knowledge transfer from the atlas to new data. Applications in mosaic integration, pseudotime analysis, and cross-tissue knowledge transfer on bone marrow mosaic datasets demonstrate the versatility and superiority of MIDAS.

bioinformatics↗

bioRxiv2022

Myeloid-specific KDM6B inhibition sensitizes Glioblastoma to PD1 blockade

Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated high expression of an epigenetic enzyme - histone 3 lysine 27 demethylase (KDM6B) in intra- tumoral immune-suppressive myeloid cell subsets. Importantly, myeloid-cell specific Kdm6b deletion enhanced pro-inflammatory pathways and improved survival in GBM tumor-bearing mice. Mechanistic studies elucidated that the absence of Kdm6b enhances antigen-presentation, interferon response and phagocytosis in myeloid cells by inhibiting mediators of immune suppression including Mafb, Socs3 and Sirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype of Kdm6b deleted myeloid cells and enhanced anti-PD1 efficacy. Thus, this study identified KDM6B as an epigenetic regulator of the functional phenotype of myeloid cell subsets and a potential therapeutic target to improve response to ICT.

immunology↗

bioRxiv2022

The endogenous modulation of visual plasticity in human adults

The adult human visual system can exhibit a degree of neuroplastic change under the right conditions which has implications for future treatments to recover vision loss that have occurred in infancy. The exogenous factors that promote neuroplastic change have been the focus of human psychophysical, electrophysiological and neuroimaging research over the last decade. What has not been considered is the importance of endogenous factors. In this study we modulate the neural oscillations that determines the internal neural state to demonstrate that endogenous factors play a critical role in not only baseline contrast sensitivity but also the extent to which the adult visual system can undergo neuroplastic change in binocular balance.

neuroscience↗

bioRxiv2022

Distinct Heterogeneity in the Naive T cell Compartments of Children and Adults

AbstractThe naive T cell compartment undergoes multiple changes across age that associate with altered susceptibility to infection and autoimmunity. In addition to the acquisition of naive-like memory T cell subsets, mouse studies describe substantial molecular reprogramming of the naive compartment in adults compared with adolescents. However, these alterations are not well delineated in human aging. Using a new trimodal single cell technology (TEA-seq), we discovered that the composition and transcriptional and epigenetic programming of the naive T cell compartment in children (11-13 yrs) is distinct from that of older adults (55-65 yrs). Naive CD4 T cells, previously considered relatively resistant to aging, exhibited far more pronounced molecular reprogramming than naive CD8 T cells, in which alterations are preferentially driven by shifts in naive-like memory subsets. These data reveal the complex nature of the naive T cell compartment that may contribute to differential immune responses across the spectrum of human age. One Sentence SummaryThe naive CD8 and CD4 T cell compartments in humans are heterogeneous and impacted differently with age, in which naive CD8 T cell subsets dramatically shift in composition and true naive CD4 T cells display significant molecular re-programming.

immunology↗

bioRxiv2022

An Integrated Physiological, Cytology and Proteomics Reveals Network of Sugarcane Protoplasts Responses to Enzymolysis

The protoplast experimental system has been becoming a powerful tool for functional genomics and cell fusion breeding. However, the physiology and molecular mechanism during enzymolysis is not completely understood and has become a major obstacle to protoplast regeneration. Our study used physiological, cytology, iTRAQ (Isobaric Tags for Relative and Absolute Quantification) -based proteomic and RT-PCR analyses to compare the young leaves of sugarcane (ROC22) and protoplasts of more than 90% viability. We found that oxidation product MDA content increased in the protoplasts after enzymolysis and several antioxidant enzymes such as POD, CAT, APX, and O2- content significantly decreased. The cytology results showed that after enzymolysis, the cell membranes were perforated to different degrees, the nuclear activity was weakened, the nucleolus structure was not obvious, and the microtubules depolymerized and formed many short rod-like structures in protoplasts. The proteomic results showed that 1,477 differential proteins were down-regulated and 810 were up-regulated after enzymolysis of sugarcane young leaves. The GO terms, KEGG and KOG enrichment analysis revealed that differentially abundant proteins were mainly involved in bioenergetic metabolism, cellular processes, osmotic stress, and redox homeostasis of protoplasts, which would allow protein biosynthesis or / degradation. The RT-PCR analysis revealed the expression of osmotic stress resistance genes such as DREB, WRKY, MAPK4, and NAC were up-regulated. Meanwhile, the expression of key regeneration genes such as CyclinD3, CyclinA, CyclinB, Cdc2, PSK, CESA and GAUT were significantly down-regulated in the protoplasts. Hierarchical clustering, identification of redox proteins and oxidation products showed that these proteins were involved in dynamic networks in response to oxidative stress after enzymolysis. We used a variety of methods to figure out how young sugarcane leaves react to enzymes.

cell biology↗

bioRxiv2022

Context-dependent requirement of G protein coupling for Latrophilin-2 in target selection of hippocampal axons

The formation of neural circuits requires extensive interactions of cell-surface proteins to guide axons to their correct target neurons. Trans-cellular interactions of the adhesion G protein-coupled receptor latrophilin-2 (Lphn2) with its partner teneurin-3 instruct the precise assembly of hippocampal networks by reciprocal repulsion. Lphn2 acts as a receptor in distal CA1 neurons to direct their axons to proximal subiculum, and as a repulsive ligand in proximal subiculum to direct proximal CA1 axons to distal subiculum. It remains unclear if Lphn2-mediated intracellular signaling is required for its role in either context. Here, we show that Lphn2 couples to G12/13 in heterologous cells, which is increased by constitutive exposure of the tethered agonist. Specific mutations of Lphn2s tethered agonist region disrupt its G protein coupling and autoproteolytic cleavage, whereas mutating the autoproteolytic cleavage site prevents cleavage but preserves a functional tethered agonist. Using an in vivo misexpression assay, we demonstrate that wild-type Lphn2 misdirects proximal CA1 axons to proximal subiculum and that Lphn2 tethered agonist activity is required for its role as a repulsive receptor. By contrast, neither tethered agonist activity nor autoproteolysis was necessary for Lphn2s role as a repulsive ligand. Thus, tethered agonist activity is required for Lphn2-mediated neural circuit assembly in a context-dependent manner.

developmental biology↗

bioRxiv2022

lncRNA-WAL Promotes Aggressiveness of Triple-Negative Breast Cancer via inducing β-Catenin nuclear translocation.

Because of its insensitive to existing radiotherapy, chemotherapy and targeted treatments, Triple-negative breast cancer (TNBC) remains a great challenge to overcome. More and more evidence has indicated abnormal wnt/{beta}-catenin pathway activation in TNBC but not luminal or her2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between Activated and inactivated Wnt/{beta}-catenin pathway of TNBC tissues, lnc-WAL (Wnt/{beta}-catenin associated lncRNA; WAL) was selected as the top up-regulated lncRNA in Wnt/{beta}-catenin pathway activation compared with the inactivation group. RIP-seq was analyzed between {beta}-catenin and IgG groups of, where lnc-WAL could interact with {beta}-catenin. Clinically, increased lnc-WAL in the TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted the EMT, the ability of breast cancer stem cells (BCSC), proliferation, migration and invasion of TNBC cells. Mechanistically, lnc-WAL inhibited {beta}-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, {beta}-catenin was accumulated in nuclear and activated the target genes. Importantly, Wnt/{beta}-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/{beta}-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL maybe as potential therapeutic target against TNBC.

genetics↗

bioRxiv2022

Metaplasticity: Dark exposure boosts excitability and visual plasticity in adult human cortex

AO_SCPLOWBSTRACTC_SCPLOWAn interlude of dark exposure for about one week is known to shift the excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting cortical plasticity across species and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies on humans remains elusive. Here, we use magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60-min dark exposure, and measure binocular combination as a behavioral assay to assess visual plasticity in 18 normally sighted human adults (13 females). To induce neuroplastic changes in the observers, 60-min monocular deprivation was performed, which is known to shift sensory eye balance in favor of the previously deprived eye. We report that prior dark exposure strengthens cortical excitability in V1 and boosts visually plasticity in normal adults. Our findings are surprising, given the fact that the interlude is very brief. We present direct evidence that an environmental manipulation that reduces intracortical inhibition can act as a metaplastic facilitator for visual plasticity in adult humans.

neuroscience↗

bioRxiv2022

Oncogenic EFNA4 amplification promotes lung adenocarcinoma lymph node metastasis

Lymph nodes metastases are common in patients with lung cancer. And those patients are often at a higher risk for death from lung tumor than those with tumor-free lymph nodes. So-matic DNA alterations are key drivers of cancer, and copy number alterations (CNAs) are a major type of DNA alteration that promotes lung cancer progression. Here, we performed genome-wide DNA copy number analysis, and identified a novel lung cancer metastasis related gene, EFNA4. EFNA4 genome locus was significantly amplified and EFNA4 mRNA expression was significantly up-regulated in lung cancer compared with normal lung tissue, and also in lung cancer with lymph node metastases compared with lung cancer without metastasis. EFNA4 encodes Ephrin A4, which is the ligand for Eph receptors. The function of EFNA4 in human lung cancer remains largely unknown. Through cell line experiments we showed that EFNA4 overexpression contributes to lung tumor cells growth, migration and adhesion. Conversely, EFNA4 knockdown or knockout led to the growth suppression of cells and tumor xenografts in mice. Lung cancer patients with EFNA4 over-expression have poor prognosis. Together, by elucidating a new layer of the role of EFNA4 in tumor proliferation and migration, our study demonstrates a better understanding of the function of the significantly amplified and overexpressed gene EFNA4 in lung tumor metastasis and suggests EFNA4 as a potential target in metastatic lung cancer therapy. Simple SummaryLymph nodes are likely to be the first stop for lung cancer metastasis. To further investigate the mechanism of lung cancer lymph node metastasis, we performed cancer genome analysis and found that EFNA4, a member of the ephrin (EPH) family, is amplified and up-regulated in lung tumor patients, especially in patients with lymph node metastases. In vitro and in vivo experiments show that overexpression of EFNA4 promotes lung tumor cell proliferation and migration, while knockdown or knockout of EFNA4 inhibits cell proliferation and migration. Altogether, our results suggest that the DNA amplification of EFNA4 genome locus could play an oncogenic function in promoting lung cancer lymph node metastasis.

cancer biology↗

bioRxiv2022

Estimating temporally variable selection intensity from ancient DNA data with the flexibility of modelling linkage and epistasis

Innovations in ancient DNA (aDNA) preparation and sequencing technologies have exponentially increased the quality and quantity of aDNA data extracted from ancient biological materials. The additional temporal component from the incoming aDNA data can provide improved power to address fundamental evolutionary questions like characterising selection processes that shape the phenotypes and genotypes of contemporary populations or species. However, utilising aDNA to study past selection processes still involves considerable hurdles like how to eliminate the confounding factor of genetic interactions in the inference of selection. To address this issue, we extend the approach of He et al. (2022) to infer temporally variable selection from the aDNA data in the form of genotype likelihoods with the flexibility of modelling linkage and epistasis in this work. Our posterior computation is carried out by a robust adaptive version of the particle marginal Metropolis-Hastings algorithm with a coerced acceptance rate. Our extension inherits the desirable features of He et al. (2022) such as modelling sample uncertainty resulting from the damage and fragmentation of aDNA molecules and reconstructing underlying gamete frequency trajectories of the population. We evaluate its performance through extensive simulations and show its utility with an application to the aDNA data from pigmentation loci in horses.

genetics↗

bioRxiv2022

Estimating temporally variable selection intensity from ancient DNA data

Novel technologies for recovering DNA information from archaeological and historical specimens have made available an ever-increasing amount of temporally spaced genetic samples from natural populations. These genetic time series permit the direct assessment of patterns of temporal changes in allele frequencies, and hold the promise of improving power for the inference of selection. Increased time resolution can further facilitate testing hypotheses regarding the drivers of past selection events such as the incidence of plant and animal domestication. However, studying past selection processes through ancient DNA (aDNA) still involves considerable obstacles such as postmortem damage, high fragmentation, low coverage and small samples. To circumvent these challenges, we introduce a novel Bayesian framework for the inference of temporally variable selection based on genotype likelihoods instead of allele frequencies, thereby enabling us to model sample uncertainties resulting from the damage and fragmentation of aDNA molecules. Also, our approach permits the reconstruction of the underlying allele frequency trajectories of the population through time, which allows for a better understanding of the drivers of selection. We evaluate its performance through extensive simulations and demonstrate its utility with an application to the ancient horse samples genotyped at the loci for coat colouration. Our results reveal that incorporating sample uncertainties can further improve the inference of selection.

genetics↗

bioRxiv2022

Temporal single cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury

Non-neuronal cells play key roles in the complex cellular interplay that follows central nervous system (CNS) insult. To understand this interplay at a tissue level, we generated a single-cell atlas of immune, glial and retinal pigment epithelial cells from adult mouse retina before and at multiple time points after axonal transection (optic nerve crush; ONC), identifying rare and undescribed subsets, and delineating changes in cell composition, expression programs, and interactions. Computational analysis charted an inflammatory cascade after injury with three phases. The early phase consisted of reactivation of retinal macroglia and microglia, providing chemotactic signals for immune infiltration, concurrent with infiltration of CCR2+ monocytes from the circulation. In the second phase, these differentiated to macrophage subsets resembling resident border-associated macrophages. In parallel, a multicellular interferon program, likely driven by microglia-derived type-I interferon, was synchronously activated across resident glia, expanding beyond rare interferon-responding subsets of glia unexpectedly present in the naive retina. Our findings provide insights regarding post-injury CNS tissue dynamics and a framework to decipher cellular circuitry, spatial relationships and molecular interactions following tissue injury.

immunology↗

bioRxiv2022

Mechanical vibration modulates regional cerebral blood flow and biomechanical co-variance network in a frequency-dependent manner

Human brain experiences vibration of certain frequency during various physical activities such as vehicle transportation and machine operation or accidents, which may cause traumatic brain injury or other brain diseases. However, little is known about what happened to brain after vibration stimuli. Here, with a custom-built electromagnetic actuator, vibration was induced in the brain while cerebral blood flow (CBF) and brain stiffness were measured at 20, 30, 40 Hz for 52 healthy volunteers. With increasing frequency, multiple regions of the brain showed increasingly reduced CBF, while the size of such regions also expanded. The vibration-induced CBF reduction regions largely fell inside the brains default mode network (DMN), with about 58 or 46 % overlap at 30 or 40 Hz, respectively. By establishing a biomechanical co-variance network based on tissue stiffness, analysis of small-world properties and modularity showed an increased disruption of the network with increased frequency. These findings demonstrate frequency-dependent features of vibration modulation to brain. Furthermore, the overlap between CBF reduction regions and DMN, and the vibration-induced decrease of biomechanical network connections suggest a interweaved relationship between blood flow, tissue stiffness, and cognitive functions. These may provide critical insights into the mechanical stimulus to brain and vibration-induced brain pathologies.

neuroscience↗

bioRxiv2022

Integrated analysis of intestinal microbiota and metabolomic reveals that decapod iridescent virus 1 (DIV1) infection induces secondary bacterial infection and metabolic reprogramming in Marsupenaeus japonicus

In recent years, with global warming and increasing marine pollution, some novel marine viruses have become widespread in the aquaculture industry, causing huge losses to the aquaculture industry. Decapod iridescent virus 1 (DIV1) is one of the newly discovered marine viruses that has been reported to be detected in a variety of farmed crustacean and wild populations. Previous studies have found that DIV1 can induce the Warburg effect. To further explore the effect of DIV1-induced metabolic reprogramming on Marsupenaeus japonicus intestinal metabolome and microbiota and the consequence on immune response, histological analysis, enzyme activity analysis and the integrated analysis of intestinal microbiome and metabolomics were performed in this study. The results showed that obvious injury in the intestinal mucosa was observed after DIV1 infection. The oxidative and antioxidant capacity of the shrimp intestine was unbalanced, the activity of lysozyme was decreased, and the activities of digestive enzymes were disordered, causing secondary bacterial infection. In addition, the increased abundance of harmful bacteria, such as Photobacterium and Vibrio, synergized with DIV1 to promote the Warburg effect and induce metabolic reprogramming, thereby providing material and energy for DIV1 replication. This study is the first to report the changes of intestinal microbiota and metabolites of M. japonicus under DIV1 infection, demonstrating that DIV1 can induce secondary bacterial infection and metabolic reprogramming, and several highly related bacteria and metabolites were screened as biomarkers. These biomarkers can be leveraged for diagnosis of pathogenic infections or incorporated as exogenous metabolites to enhance immune response.

microbiology↗