Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transferrable protection by gut microbes against STING-associated lung disease.

ABSTRACT: STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans and mice with STING gain-of-function mutations develop a syndrome known as STING-associated vasculopathy with onset in infancy (SAVI), which is characterized by inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of gain-of-function STING to bacterial CDNs might explain autoinflammatory lung disease in SAVI mice. We report that depletion of gut microbes with oral antibiotics (vancomycin, neomycin, and ampicillin [VNA]) nearly eliminates lung disease in SAVI mice, implying that gut microbes might promote STING-associated autoinflammation. However, we show that germ-free SAVI mice still develop severe autoinflammatory disease and that transferring gut microbiota from antibiotics-treated mice to germ-free animals eliminates lung inflammation. Depletion of anaerobes with metronidazole abolishes the protective effect of the VNA antibiotics cocktail, and recolonization with the metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming a protective role of a metronidazole-sensitive microbe in a model of SAVI.

SUBMITTER: Platt DJ

PROVIDER: S-EPMC8477380 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Protection against STING-associated lung disease

Project description:Transferrable protection by gut microbes against STING-associated lung disease

| PRJEB42379 | ENA

Parkinson's disease: Are gut microbes involved?

Project description: Not available

| S-EPMC8087343 | biostudies-literature

Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling.

Project description:Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173-/-) and cGAS-knockout (Mb21d1-/-) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS-STING-IFN-I pathway. Cyclic-di-AMP - an emerging second messenger of bacteria - may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.

| S-EPMC9467592 | biostudies-literature

Interstitial Lung Disease Caused by STING-associated Vasculopathy with Onset in Infancy.

Project description: Not available

| S-EPMC5027210 | biostudies-literature

Human Gut Microbes Associated with Systolic Blood Pressure.

Project description:Emerging studies have revealed a strong link between the gut microbiome and several human diseases. Since human gut microbiome mirrors variations in lifestyle and environment, whether associations between disease conditions and gut microbiome are consistent across populations-particularly in communities practicing traditional subsistence strategies whose microbiomes differ markedly from industrialists-remains unknown. Cardiovascular diseases are the leading cause of mortality in India affecting 55 million people, and high blood pressure is one of the primary risk factors for cardiovascular diseases. We examined associations between gut microbiome and blood pressure along with 14 other variables associated with lifestyle, dietary habits, disease conditions, and clinical blood markers in the three Assamese populations. Our analysis reveals a robust link between the gut microbiome diversity and composition and systolic blood pressure. Moreover, several genera previously associated with hypertension in non-Indian populations were also associated with systolic blood pressure in this cohort and these genera were predictors of elevated blood pressure in these populations. These findings confer opportunities to design personalized, preventative, and targeted interventions harnessing the gut microbiome to tackle the burden of cardiovascular diseases in India.

| S-EPMC8831042 | biostudies-literature

Engineered Stochastic Adhesion Between Microbes as a Protection Mechanism Against Environmental Stress.

Project description:IntroductionMicrobes aggregate when they display adhesive proteins on their outer membrane surfaces, which then form bridges between microbes. Aggregation protects the inner microbes from harsh environmental conditions such as high concentrations of antibiotics, high salt conditions, and fluctuations in pH. The protective effects of microbial aggregation make it an attractive target for improving the ability of probiotic strains to persist in the gut environment. However, it remains challenging to achieve synthetic microbial aggregation using natural adhesive proteins because these proteins frequently mediate microbial virulence.ObjectivesConstruction of synthetic proteins that mediate aggregation between microbes to enhance the survival of cells delivered to stressful environments.MethodsWe construct synthetic adhesins by fusing adhesive protein domains to surface display peptides. The resulting aggregated populations of bacteria are characterized using immunofluorescence, microscopy, flow cytometry, and quantification of colony forming units.ResultsWe assemble a series of synthetic adhesins, demonstrate their display on the outer membrane of Escherichia coli, and show that they mediate bacterial aggregation. Further engineering of the size and motif composition of the adhesive domain shows that principles from natural adhesins can be applied to our synthetic adhesins. Finally, we show that aggregation allows E. coli cells to resist treatment with antimicrobial peptides and survive inside the gut of Caenorhabditis elegans.ConclusionsOur results demonstrate that synthetic aggregation can allow bacteria to resist biocidal environmental conditions. Synthetic adhesins may be used to facilitate microbial colonization of previously inaccessible environmental niches, either in remote natural environments or inside living organisms.

| S-EPMC6816592 | biostudies-literature

Vaccine-mediated protection against <i>Campylobacter</i>-associated enteric disease.

Project description:Campylobacter coli and Campylobacter jejuni are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. Despite its global importance, Campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring Campylobacter-associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation H2O2-based Campylobacter vaccines that induced strong antibacterial antibodies to multiple Campylobacter proteins including flagellin and provided up to 83% protection against severe C. coli-associated diarrhea. Whole-genome sequencing of circulating Campylobacter strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the Campylobacter vaccine strains used in these studies, indicating that vaccine-mediated immunity was not restricted to a single homologous serotype. Together, these results demonstrate an important advance in vaccine development and a new approach to reducing Campylobacter-associated enteric disease.

| S-EPMC7314533 | biostudies-literature

Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid.

Project description:Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.

| S-EPMC10392757 | biostudies-literature

Synthesis of rotenone loaded zein nano-formulation for plant protection against pathogenic microbes.

Project description:Rotenone (RN) is a naturally occurring isoflavone found in the root or rhizomes of fabaceae (a plant family), known for its insecticidal/pesticidal properties. Rotenone was loaded in zein nanoparticles (ZSC) by antisolvent precipitation method at room temperature. The synthesized nanoparticles showed self-assembled spherical nanostructures having 425.67 ± 7.02 and 471.33 ± 10.60 nm of hydrodynamic radii with -14.23 ± 0.21 and -17.64 ± 0.89 mV zeta potential for ZSC and RNZSC (rotenone loaded zein nanoparticles), respectively. The encapsulation of rotenone was confirmed by FTIR, 1H NMR and DSC studies. A significant encapsulation efficiency of 95.82 ± 0.038% and 5.99 ± 0.002% loading efficiency were determined by HPLC studies. Synthesized RNZSC showed excellent antimicrobial activity against plant pathogens- P. syringae and F. oxysporum. Our studies showed for the first time direct evidence of antimicrobial activity of rotenone against plant pathogens. A similar approach could be adopted for developing several new botanical based nano-formulations with their known insecticidal effect, to control certain plant diseases in an environment friendly and sustainable manner.

| S-EPMC9076286 | biostudies-literature