Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE143729 | GEO | 2020/03/01
REPOSITORIES: GEO
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2012-10-30 | E-GEOD-38151 | biostudies-arrayexpress
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2019-12-30 | GSE108156 | GEO
Project description:The use of some antibiotics, including florfenicol and enrofloxacin, is allowed in aquaculture in China. Accordingly, to better address the concerns and questions associated with the impact of administered enrofloxacin and florfenicol to grass carp, here we investigated the transcriptome of the intestine of C. idella treated with these oral antibiotics. The aim of this study was to provide an in-depth evaluation of the antibiotic-induced patterns and dynamics of the microbiota grass carp and the potential mechanism involved.
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Project description:Kaiser2014 - Salmonella persistence after ciprofloxacin treatment
The model describes the bacterial tolerance to antibiotics. Using a mouse model for Salmonella diarrhea, the authors have found that bacterial persistence occurs in the presence of the antibiotic ciprofloxacin because Salmonella can exist in two different states. One, the fast-growing population that spreads in the host's tissues and the other, slow-growing "persister" population that hide out inside dendritic cells of the host's immune system and cannot be attacked by the antibiotics. However, this can be killed by adding agents that directly stimulate the host's immune defense.
This model is described in the article:
Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.
Kaiser P, Regoes RR, Dolowschiak T, Wotzka SY, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt WD.
PLoS Biol. 2014 Feb 18;12(2):e1001793.
Abstract:
In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.
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2014-03-25 | BIOMD0000000527 | BioModels
Project description:Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
2015-05-07 | GSE68603 | GEO
Project description:Disrupted interactions between host and intestinal bacteria are implicated in the development of colorectal cancer (CRC). However, the functional impacts of these inter-kingdom interactions remain poorly defined. To examine this interplay, we performed small RNA sequencing on the stool of from germ-free (GF) and gnotobiotic ApcMin/+;Il10-/- mice associated with microbes from biofilm-positive human CRC tumor (BT) and biofilm-negative healthy (BX) tissues. revealed a group of significant differentially expressed miRNAs specific to BT compared to BX associated ApcMin/+;Il10-/- mice and several miRNAs that correlated with bacterial genera abundances. Our findings suggest complex interactions within bacterial communities affecting host-derived miRNA and CRC development.
2019-12-30 | GSE108164 | GEO
Project description:Background: While the luminal microbiome composition in the human cervicovaginal tract has been defined, the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that they may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a clinically well-characterized cohort of Kenyan women. Results: We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners dominated luminal samples had a corresponding Gardnerella dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbiome was associated with epithelial remodeling and pro-inflammatory pathways. Communities dominated by L. iners and Gardnerella were associated with low host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, and with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity. Conclusion: We identified ectocervical tissue-adherent bacterial communities in all study participants. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. This difference could possibly explain that L. iners dominant luminal communities have a high probability of transitioning to high diverse bacterial communities including high abundance of Gardnerella. By performing integrative multi-omics analyses we further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community is similar to vaginal biofilms that significantly impact women’s reproductive and sexual health.
2023-02-10 | GSE194276 | GEO
Project description:Escherichia coli (E. coli) urinary tract infections (UTIs) are becoming a serious problem both for pets and humans (zoonosis) due to the close contact and to the increasing resistance to antibiotics. Great progress has been made in the discovery of novel antibiotics to counteract E. coli pathogens. However, this huge progress has been undercut by the evolution of bacteria in the way of drug resistance. Enrofloxacin is one of the most efficient antibiotics against E. coli pathogens and there is considerable evidence that documents how this microorganism is becoming more resistant to this antibiotic and is developing multidrug resistance. This study has been performed in order to unravel the mechanism of induced enrofloxacin resistance in canine E. coli isolates that represent a good tool to study this pathology. For a comprehensive investigation about antibiotic resistance mechanisms, an E. coli isolate from urinary tract infection (UTI) was induced to grow under a concentration of 10 µg/ml of enrofloxacin. Proteins represent the main contributors to the mechanisms involved in antibiotic resistance in bacteria. Their abundance profile provides reliable information about the mechanisms involved in this process. Three biological replicates of control and resistant isolate have been analyzed both through 2D DIGE and shotgun proteomics. In our case, prior to perform the proteomics analysis, the screening with MS profiling of control and resistant isolates was performed highlighting the differences among strains and successfully clustering experimental strains according to PC analysis (PCA). The results clearly demonstrate differential profiles in peptide expression among clusters and between isolate and reference strain. According to these preliminary results, the protein profile of the resistant group was compared with the one of its sensitive counterpart by a proteomic analysis based on 2D-DIGE to separate proteins combined to MALDI MS analysis and database search to identify differentially expressed proteins. This analysis showed the modulation of 19 proteins between the two conditions. At the same time, another comparative proteomics investigation was also carried out by free-label nLC-MSE. This method has allowed the qualitative and quantitative analysis of total protein extracts of the two groups for the simultaneous screening of a larger number of proteins. A total of 57 differentially expressed proteins were identified and a comprehensive study on the proteins associated with enrofloxacin resistance was carried out. We classified these modulated proteins by their molecular functions and pathways where they are principally involved. This approach allowed to highlight some pathways that can be involved in an increased antibiotic resistance. Two major mechanisms were discovered. The first one was related to the stabilization of DNA structure through the up-regulation of Dsp protein. The second one was the downregulation of outer membrane protein W in order to reduce the membrane permeability to enrofloxacin. Discovered differentilally expressed proteins are principally involved in antibiotic resistance and linked to the oxidative stress response, to DNA protection and in membrane permeability. Moreover, since enrofloxacin is an inhibitor of DNA gyrase, the overexpression of DNA starvation/stationary phase protection protein (Dsp) could be a central point to discover the mechanism of this clone to counteract the effects of enrofloxacin. In parallel, the dramatic decrease of the synthesis of the outer membrane protein W, which represents one of the main gates for enrofloxacin entrance, could explain additional mechanism of E. coli defense against this antibiotic. The proteins differentially expressed could represent putative targets for the development of new strategies to counteract drug and multidrug resistance.
2015-06-05 | PXD002000 | Pride