Biology subjects

Wu, G.

Publications and source records attributed to Wu, G..

At least 163 records · Page 9Linked to original sources

bioRxiv2020

Cross-regulation between RpfG and HtsHs to regulate antibiotic biosynthesis in Lysobacter

Bacterial two-component systems (TCSs) sense and respond to environmental changes and modulate downstream gene expression. However, the mechanism of cross-talk between multiple TCSs is unclear. In this study, we report a previously uncharacterized mechanism by which the TCS protein RpfG interacts with hybrid two-component system (HyTCS) proteins HtsH1, HtsH2 and HtsH3 to regulate antibiotic biosynthesis in Lysobacter. RpfG, a phosphodiesterase (PDE), can degrade c-di-GMP to 5-pGpG and can regulate antibiotic heat-stable antifungal factor (HSAF) biosynthesis in a PDE- independent manner. Thus, we wondered whether RpfG regulate HSAF biosynthesis through interactions with other factors. Subsequently, we demonstrated that RpfG interacts with three HyTCS proteins (HtsH1, HtsH2 and HtsH3), that can inhibit the PDE enzymatic activity of RpfG. Importantly, deletion of htsH1, htsH2 and htsH3 resulted in significantly decreased HSAF production, and we showed that HtsH1, HtsH2 and HtsH3 depend on their phosphorylation activity to directly regulate HSAF biosynthesis gene expression. Our results reveal that RpfG does not depend on PDE activity to regulate HSAF biosynthesis, rather it interacts with HtsH1, HtsH2 and HtsH3 to do so, a regulatory mechanism that may be a conserved paradigm in Lysobacter and Xanthomonas.

microbiology↗

bioRxiv2020

Single-cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo

A high-resolution protein atlas is essential for understanding the molecular basis of biological processes. Using protein-fusion reporters and imaging-based single-cell analyses, we present a protein expression atlas of C. elegans embryogenesis encompassing 266 transcription factors (TFs) in nearly all (90%) lineage-resolved cells. Single-cell analysis reveals a combinatorial code and cascade that elucidate the regulatory hierarchy between a large number of lineage-, tissue-, and time-specific TFs in spatiotemporal fate patterning. Guided by expression, we identify essential functions of CEH-43/DLX, a lineage-specific TF, and ELT-1/GATA3, a well-known skin fate specifier, in neuronal specification; and M03D4.4 as a pan-muscle TF in converging muscle differentiation in the body wall and pharynx. Finally, systems-level analysis of TF regulatory state uncovers lineage- and time-specific kinetics of fate progression and widespread detours of the trajectories of cell differentiation. Collectively, our work reveals a single-cell molecular atlas and general principles underlying the spatiotemporal patterning of a metazoan embryo.

developmental biology↗

bioRxiv2020

CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity

BackgroundNatalizumab, a humanized monoclonal antibody (mAb) against 4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of 4-integrin in CD11c+ cells should curtail their migration to the CNS and ameliorate experimental autoimmune encephalomyelitis (EAE). MethodsWe generated CD11c.Cre+/-ITGA4fl/fl C57/Bl6 mice to selectively delete 4-integrin in CD11c+ cells. Active immunization and adoptive transfer EAE models were employed. Multi-parameter flow cytometry was utilized to immunophenotype leukocytes. Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells. Results4-integrin expression by CD11c+ cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre+/-ITGA4fl/fl mice. In active EAE, a delayed disease onset was observed in CD11c.Cre+/-ITGA4fl/fl mice, during which CD11c+CD88+ cells were sequestered in the blood. Upon EAE onset, CD11c+CD88+ cells accumulated in the CNS and expressed CD317+. In adoptive transfer experiments, CD11c.Cre+/-ITGA4fl/fl mice had ameliorated clinical disease associated with diminished numbers of CNS CD11c+CD88+CD317+ cells. The transcription profile of CD11c+CD88+CD317+ cells placed them within previously defined microglia-like cells in human CSF. We show that activated, but not naive microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery. ConclusionCD11c+CD88+CD317+ cells in the CNS promote inflammatory damage. Transcriptional analysis identifies CD11c+CD88+CD317+ cells as a unique myeloid subset in human CSF. The disease-propagating effects of these cells can be antagonized using anti-CD317 mAb.

immunology↗

bioRxiv2020

Ontogeny and function of the circadian clock in intestinal organoids

Circadian rhythms regulate diverse aspects of gastrointestinal physiology ranging from the composition of microbiota to motility. However, development of the intestinal circadian clock and detailed molecular mechanisms regulating circadian physiology of the intestine remain largely unknown. The lack of appropriate human model systems that enable organ- and/or diseasespecific interrogation of clock functions is a major obstacle hindering advancements of translational applications using chronotherapy. In this report, we show that both pluripotent stem cell-derived human intestinal organoids engrafted into mice and patient-derived human intestinal enteroids (HIEs) possess robust circadian rhythms, and demonstrate circadian phase-dependent necrotic cell death responses to Clostridium difficile toxin B (TcdB). Intriguingly, mouse and human enteroids demonstrate anti-phasic necrotic cell death responses. RNA-Seq data show ~4% of genes are rhythmically expressed in HIEs. Remarkably, we observe anti-phasic gene expression of Rac1, a small GTPase directly inactivated by TcdB, between mouse and human enteroids. Importantly, the observed circadian time-dependent necrotic cell death response is abolished in both mouse enteroids and human intestinal organoids (HIOs) lacking robust circadian rhythms. Our findings uncover robust functions of circadian rhythms regulating critical clock-controlled genes (CCGs) in human enteroids governing organism-specific, circadian phasedependent necrotic cell death responses. Our data highlight unique differences between mouse and human enteroids, and lay a foundation for human organ- and disease-specific investigation of clock functions using human organoids for translational applications.

molecular biology↗

bioRxiv2020

New gene association measures by joint network embedding of multiple gene expression datasets

Large number of samples are required to construct a reliable gene co-expression network, the samples from a single gene expression dataset are obviously not enough. However, batch effect may widely exist among datasets due to different experimental conditions. We proposed JEBIN (Joint Embedding of multiple BIpartite Networks) algorithm, it can learn a low-dimensional representation vector for each gene by integrating multiple bipartite networks, and each network corresponds to one dataset. JEBIN owns many inherent advantages, such as it is a nonlinear, global model, has linear time complexity with the number of genes, dataset or samples, and can integrate datasets with different distribution. We verified the effectiveness and scalability of JEBIN through a series of simulation experiments, and proved better performance on real biological data than commonly used integration algorithms. In addition, we conducted a differential co-expression analysis of hepatocellular carcinoma between the single-cell and bulk RNA-seq data, and also a contrast between the hepatocellular carcinoma and its adjacency samples using the bulk RNA-seq data. Analysis results prove that JEBIN can obtain comprehensive and stable gene co-expression networks through integrating multiple datasets and has wide prospect in the functional annotation of unknown genes and the regulatory mechanism inference of target genes.

bioinformatics↗

bioRxiv2020

Short-term exposure to intermittent hypoxia in mice leads to changes in gene expression seen in chronic pulmonary disease

Obstructive sleep apnea (OSA) results from episodes of airway collapse and intermittent hypoxia and is associated with a host of health complications including dementia, diabetes, heart failure, and stroke. Although the lung is the first organ to sense changes in inspired oxygen levels, little is known about the consequences of IH to the lung hypoxia-inducible factor (HIF)-responsive pathways. Furthermore, cellular mechanisms causing disease progression across multiple systems in OSA are unknown. We hypothesized that exposure to IH would lead to up- and down-regulation of diverse expression pathways and that individual cell populations would show distinctive responses to IH. We identify changes in circadian and immune pathways in lungs from mice exposed to IH. Among all cell types, endothelial cells show the most prominent transcriptional changes. Interestingly, up-regulated genes in endothelial, fibroblast, and myofibroblast cells were enriched for genes associated with pulmonary fibrosis and pulmonary hypertension. These genes include targets of several drugs currently used to treat chronic pulmonary diseases. Our results reveal potential candidates for cell-targeted therapy seeking to minimize pulmonary effects of OSA. A better understanding of the pathophysiologic mechanisms underlying diseases associated with OSA could improve our therapeutic approaches, directing therapies to the most relevant cells and molecular pathways.

pathology↗

bioRxiv2020

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

BackgroundThe 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. MethodsWe collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. ResultsSystematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. ConclusionsOur studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence SummaryNovel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

microbiology↗

bioRxiv2020

The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

microbiology↗

bioRxiv2020

Altered Temporal Variability of Local and Large-scale Resting-state Brain Functional Connectivity Patterns in Schizophrenia and Bipolar Disorder

Schizophrenia and bipolar disorder share some common clinical features and are both characterized by aberrant resting-state functional connectivity (FC). However, little is known about the common and specific aberrant features of the dynamic FC patterns in these two disorders. In this study, we explored the differences in dynamic FC among schizophrenia patients (n = 66), type I bipolar disorder patients (n = 53) and healthy controls (n = 66), by comparing temporal variabilities of FC patterns involved in specific brain regions and large-scale brain networks. Compared with healthy controls, both patient groups showed significantly increased regional FC variabilities in subcortical areas including the thalamus and basal ganglia, as well as increased inter-network FC variability between the thalamus and sensorimotor areas. Specifically, more widespread changes were found in the schizophrenia group, involving increased FC variabilities in sensorimotor, visual, attention, limbic and subcortical areas at both regional and network levels, as well as decreased regional FC variabilities in the default-mode areas. The observed alterations shared by schizophrenia and bipolar disorder may help to explain their overlapped clinical features; meanwhile, the schizophrenia-specific abnormalities in a wider range may support that schizophrenia is associated with more severe functional brain deficits than bipolar disorder.

neuroscience↗

bioRxiv2019

A single-sample circadian biomarker that performs across populations and platforms

BackgroundFor circadian medicine to influence health, such as when to take a drug or undergo a procedure, a practical way to measure body time is needed. Recent machine learning algorithms show that gene expression data from blood and skin can provide reliable estimates of body time. However, for clinical viability, a biomarker must be easily measured and generalizable to a broad population. It is not clear that any circadian biomarker yet satisfies these criteria.\n\nResultsWe analyzed 24 h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal and population data. Circadian clock function was strongest in the epidermis, regardless of body site. We identified a 12-gene biomarker set that reported circadian phase to within 3 hours from a single sample of epidermis--the skins most superficial layer. This set performed well across body sites, ages, sexes, and detection platforms.\n\nConclusionsThis research shows that the clock in epidermis is more robust than dermis regardless of body site. To encourage ongoing validation of this biomarker in diverse populations, diseases, and experimental designs, we developed SkinPhaser--a user-friendly app to test biomarker performance in datasets (https://github.com/gangwug/SkinPhaser).

systems biology↗

bioRxiv2019

The genome of the butternut canker pathogen, Ophiognomonia clavigignenti-juglandacearum shows an elevated number of genes associated with secondary metabolism and protection from host resistance responses in comparison with other members of the Diaporthales

Ophiognomonia clavigignentijuglandacearum (Oc-j) is a plant pathogenic fungus that causes canker and branch dieback diseases in the hardwood tree butternut, Juglans cinerea. Oc-j is a member of the order of Diaporthales, which includes many other plant pathogenic species, several of which also infect hardwood tree species. In this study, we sequenced the genome of Oc-j and achieved a high-quality assembly and delineated the phylogeny of Oc-j within the Diaporthales order using a genome-wide multi-gene approach. We also further examined multiple gene families that might be involved in plant pathogenicity and degradation of complex biomass, which are relevant to a pathogenic life-style in a tree host. We found that the Oc-j genome contains a greater number of genes in these gene families compared to other species in Diaporthales. These gene families include secreted CAZymes, kinases, cytochrome P450, efflux pumps, and secondary metabolism gene clusters. The large numbers of these genes provide Oc-j with an arsenal to cope with the specific ecological niche as a pathogen of the butternut tree.

genomics↗

bioRxiv2019

Variations of gut microbiome profile under different storage conditions and preservation periods: A multi-dimensional evaluation

Gut dysbiosis contributes to the development of various human diseases. There are thousands of publications per year for investigating the role of gut microbiota in development of various diseases. However, emerging evidence has indicated data inconsistency between different studies frequently, but gained very little attention by scientists. There are many factors that can cause data variation and inconsistency during the process of microbiota study, in particular, sample storage conditions and subsequent sequencing process. Here, we systemically evaluated the impacts of six fecal sample storage conditions (including -80 {degrees}C, -80 {degrees}C with 70% ethanol (ET_-80 {degrees}C), 4{degrees}C with 70% ethanol (ET_4{degrees}C), and three commercial storage reagents including OMNIgene*GUT OMR-200 (GT), MGIEasy (MGIE), and Longsee (LS)), storage periods (1, 2 weeks or 6 months), and sequencing platform on gut microbiome profile using 16S rRNA gene sequencing. Our results suggested that -80{degrees}C is acceptable for fecal sample storage, and the addition of 70% ethanol offers some benefits. Meanwhile, we found that samples in ET_4 {degrees}Cand GT reagents are comparable, both introduced multi-dimensional variations. The use of MGIE resulted in the least alteration, while the greatest changes were observed in samples stored in LS reagents during the whole experiment. Finally, we also confirmed that variations caused by storage condition were larger than that of storage time and sequencing platform.\n\nIMPORTANCEIn the current study, we performed a multi-dimensional evaluation on the variations introduced by types of storage conditions, preservation period and sequencing platform on the basis of data acquired from 16S rRNA gene sequencing. The efficacy of preservation methods was comprehensively evaluated by DNA yield and quality, and {beta} diversity, relative abundance of the dominant bacteria and functional bacteria associated with SCFAs producing and BAs metabolism. Our results confirmed that variations introduced by storage condition were larger than that of storage periods and sequencing platform. Collectively, our study provided a comprehensive view to the impacts of storage conditions, storage times, and sequencing platform on gut microbial profile.

microbiology↗

bioRxiv2019

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, non-visual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocyte-specific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.

physiology↗

bioRxiv2019

A Large-scale Study Reveals 24 hour Operational Rhythms in Hospital Treatment

Hospitals operate 24 hours a day, and it is assumed that critical decisions occur continuously around the clock. However, many aspects of hospital operation occur at particular times of day, including medical team rounding and shift changes. It is unclear if this impacts patient care, as an empirical account of 24 h treatment patterns is lacking. We analyzed the daily distribution of ~120K doses of 12 separate drugs in 1,486 inpatients at a major childrens hospital in the U.S. Treatment orders and administration were strongly time-of-day-dependent, marked by distinct morning time surges and overnight lulls. These 24 h rhythms in treatment were remarkably consistent across drugs, diagnoses, and hospital units. In sum, nearly one-third of all 116,975 orders for treatment were placed between 8 AM and 12 PM. This rhythm in hospital medicine coincided with medical team rounding time, not necessarily immediate medical need. Lastly, we show that the clinical response to hydralazine, an acute antihypertensive, is dosing time-dependent and greatest at night, when the fewest doses were administered. The prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and reveal a potential operational barrier to best clinical care.\n\nSIGNIFICANCE STATEMENTThe order and administration of hospital treatment was characterized by morning time surges and overnight lulls, regardless of drug type, diagnosis or care unit. As the first large-scale account of 24 h rhythms in hospital medicine, this study identifies a potential operational barrier to best clinical care. Critical clinical decisions should be made around the clock; pain, infection, hypertensive crisis, and other conditions do not occur selectively in the morning. Systemic bias in the timing of medicine is also at odds with circadian biology, which can influence when certain treatments are most effective or safe. Prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and suggest that time of day in hospital operations deserves further consideration.

epidemiology↗

bioRxiv2019

Coupling multiplex pre-amplification and droplet digital PCR for longitudinal monitoring of ESR1 and PIK3CA mutations from plasma cell-free DNA

Here we report on the development of a sensitive and cost-effective method to longitudinally track ESR1 and PIK3CA mutations from cfDNA in patients with metastatic breast cancer (MBC) using a streamlined and de-centralized workflow. Hotspot mutations in ESR1 have been shown to cause resistance to aromatase inhibitor-based and anti-estrogenic therapies, while PIK3CA mutations have high prevalence in MBC. As a result, their utility as circulating biomarkers to predict or monitor response in the clinical development of investigational compounds has been the focus of many studies. Six regions in ESR1 and PIK3CA genes containing 20 hotspot mutations were pre-amplified, followed by optimized singleplex ddPCR assays to detect allele frequencies of individual mutations. Without pre-amplification, the limit of detection (LOD) and limit of linearity (LOL) of individual ddPCR assays were at 0.05-0.1% and 0.25% level, respectively. With pre-amplification, the LOD and LOL were slightly elevated at 0.1-0.25% and 0.25-0.5% levels, respectively. High concordance was achieved to the BEAMing assay (Sysmex Inostics) for mutation positive assays (r=0.98, P<0.0001). In conclusion, coupling pre-amplification and ddPCR assays allowed us for the detection of up to 20 hot spot mutations in ESR1 and PIK3CA with high sensitivity and reproducibility.

genetics↗

bioRxiv2019

Genomic acquisitions in emerging populations of Xanthomonas vasicola pv. vasculorum infecting corn in the U.S. and Argentina

Xanthomonas vasicola pv. vasculorum (Xvv) is an emerging bacterial plant pathogen that causes bacterial leaf streak on corn. First described in South Africa in 1949, reports of this bacteria have greatly increased in the past years in South America and in the U.S., where it is now present in most of the corn producing states. Phenotypic characterization showed that the emerging U.S. and South American Xvv populations may have increased virulence in corn compared to older strains. To understand the genetic mechanisms behind the increased virulence in this group, we used comparative genomics to identify gene acquisitions in Xvv genomes from the U.S. and Argentina. We sequenced 41 genomes of Xvv and the related sorghum-infecting X. vasicola pv. holcicola (Xvh). A comparison of all available X. vasicola genomes showed the phylogenetic relationships in the group and identified clusters of genes associated with the emerging Xvv populations. The newly acquired gene clusters showed evidence of horizontal transfer to Xvv and included candidate virulence factors. One cluster, in particular, corresponded to a prophage transferred from Xvh to all Xvv from Argentina and the U.S. The prophage contains putative secreted proteins, which represent candidates for virulence determinants in these populations and await further molecular characterization.

microbiology↗

bioRxiv2019

Differential and Age Dependent Expression of Specific Sialoglycans on HeLa Cells -Revealed by Direct Fluorescent Glycan Labeling

Cells are covered with glycans. The expression and distribution of specific glycans on cell surface are important for various cellular functions. Imaging these glycans is essential to elucidate their biological roles. Here, utilizing enzymatic incorporation of fluorophore-conjugated sialic acids, dubbed as direct fluorescent glycan labeling (DFGL), we report the imaging of N- and O-glycans and particularly tumor specific sialyl T antigen on HeLa cells. It is found that while Core-1 O-glycans are relatively evenly distributed on cells, the expression of N-glycans tend to be more peripheral. More interestingly, the expression of sialyl T antigen displays random and sporadic patterns. In technique side, DFGL allows convenient labeling or imaging of various glycans on intact glycoproteins or cell surfaces with variety of fluorescent dyes.

cancer biology↗

bioRxiv2019

Remodeling gut microbiota by Streptococcus thermophilus 19 attenuates inflammation in septic mice

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is the leading cause of death in burn patients. Streptococcus thermophilus 19 is a highly effective probiotic, with well-studied health benefits, but its role in protecting viscera against injury caused by sepsis and the underlying mechanism is poorly understood. The goal of this study was to evaluate protection potency of S. thermophilus against inflammation in mice and evaluate the influence of sepsis and S. thermophilus on microbial community. We tested the utility of S. thermophilus 19 in attenuating inflammation in vitro and vivo of LPS-induced sepsis mouse model. We also evaluated the influence of sepsis and S. thermophilus on microbial community. In vitro, S. thermophilus 19 decrease the expression of inflammatory factors. Additionally, in a lipopolysaccharide-induced septic mouse model, mice administered the probiotic 19 was highly resistant to Lps and exhibited decreased expression of inflammatory factors compared to Lps-treated control mice. A MiSeq-based sequence analysis revealed that gut microbiota alterations in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of oral probiotics 19. Together these findings indicate that S. thermophilus 19 may be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases. In an analysis of the gut microbiota of the all group mice, we found that sepsis is associated with gut microbiota and probiotics attenuate the inflammation through remodeling gut microbiota. ImportanceSepsis is life-threatening organ dysfunction which is the leading cause of death in burn patients. Although our understanding of sepsis has increased substantially in recent years, its still reported to be the leading cause of death in seriously ill patients. Evidences showed that gut microbiota play an important role in sepsis. Moreover, probiotics have been used to prevent numbers of gut health disorders and alleviate inflammation associated with some human diseases by promoting changes in the gut microbiota composition. Hence, to investigate the mechanism of probiotics in the treatment of sepsis has emerged. The significance of our research is in identifying the role of gut microbiota in sepsis and found an effective probiotic that reduces inflammation, S. thermophilus 19, and investigating the therapeutic effect and mechanism of S. thermophilus 19 on sepsis, which might be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases.

microbiology↗