Analysis of the fecal and oral microbiota in chronic recurrent multifocal osteomyelitis
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB22984 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disease for which a lack of bacterial involvement is a key diagnostic feature to distinguish it from other symptomatically related diseases. However, the growing evidence suggesting an involvement of the host-associated microbiota in rheumatic disorders together with the now wide accessibility of modern culture-independent methods warrant a closer examination of CRMO.MethodsIn this study, we show through bacterial 16S rRNA gene profiling that numerous features of the oral- and fecal microbial communities differentiate children with and without CRMO.ResultsNotably, communities in diseased children are characterized by a lack of potential probiotic bacteria in the fecal community and an overabundance of known pathobionts in the oral microbial communities. Of special interest is the HACEK group, a set of commonly known oral pathogens that are implicated in the development of several acute and chronic diseases such as osteitis and rheumatoid arthritis. Furthermore, we observe that gut bacterial communities in the diseased children appear to reflect an altered host physiology more strongly than the oral community, which could suggest an oral disease origin followed by propagation and/or responses beyond the oral cavity.ConclusionsBacterial communities, in particular the oral microbiota, may serve as an indicator of underlying susceptibility to CRMO, or play a yet undefined role in its development.
| S-EPMC8862485 | biostudies-literature
Project description:Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disorder that most frequently affects children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions and its waxing and waning character. Sometimes severe and chronic pain can significantly affect the quality of life and psychosocial development of individuals affected. In the absence of prospectively tested and widely accepted diagnostic criteria or disease biomarkers, CNO remains a diagnosis of exclusion, and infections, malignancy and other differentials require consideration (1). The pathophysiology of CNO is not fully understood, but imbalanced cytokine expression and increased inflammasome activation in monocytes from CNO patients contribute to a pro-inflammatory phenotype that contributes to bone inflammation (2). Currently, no medications are licensed for the use in CNO. Most patients show at least some response to nonsteroidal anti-inflammatory drugs, others require more aggressive treatment that can include corticosteroids, cytokine-blocking agents and/or bisphosphonates (3). While under the care of an experienced team and sufficient treatment, the prognosis is good, but some patients will develop sequalae which can include vertebral compression fractures (1).
| S-EPMC8040271 | biostudies-literature
Project description:Chronic recurrent multifocal osteomyelitis (CRMO) is a rare non-infectious inflammatory bone disease of unknown aetiology. CRMO mainly affects the metaphyses of long bones and spine in children and young adolescents. It presents with recurrent episodes of bone pain and fever, resembling bacterial osteomyelitis, but cultures of lesions are sterile and it is unresponsive to antibiotic therapy. We report a case of a 3-year-old boy diagnosed with CRMO, who was initially treated for bacterial osteomyelitis, and received prolonged antibiotic therapy for chronic pain, and swelling of mandible and ulna. CRMO should be kept in mind in the differential diagnosis of chronic bone pain and osteomyelitis unresponsive to antibiotic treatment.
| S-EPMC4550928 | biostudies-other
Project description:Purpose of reviewChronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO.Recent findingsThough the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues. CNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.
| S-EPMC5705736 | biostudies-literature
Project description:Purpose of reviewWe focus on recent advances in the understanding of the genetic, molecular, immunologic, and environmental factors implicated in the pathogenesis of autoinflammatory bone diseases including the syndromic and non-syndromic forms of chronic recurrent multifocal osteomyelitis (CRMO).Recent findingsEvidence implicating the IL-1 pathway in the pathogenesis of the Mendelian forms of CRMO is growing. LIPIN2 can regulate the NLRP3 inflammasome by affecting P2X7 receptor activation, and intracellular cholesterol can modulate P2X7R currents. Work in a mouse model of CRMO demonstrates that dietary manipulation can alter the microbiome and protect these mice from the development of sterile osteomyelitis in vivo. Although the genetic and immunologic basis of non-syndromic CRMO remains only partially understood, the IL-1 pathway is central to the pathogenesis in the syndromic autoinflammatory bone disorders. Recent work implicates lipids and the microbiome in sterile osteomyelitis.
| S-EPMC5545929 | biostudies-literature
Project description:ObjectiveChronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder. Its most severe form is referred to as chronic recurrent multifocal osteomyelitis (CRMO). Currently, the exact molecular pathophysiology of CNO/CRMO remains unknown. No uniform diagnostic standard and treatment protocol were available for this disease. The aim of this study was to identify the differentially expressed genes (DEGs) in CRMO tissues compared to normal control tissues to investigate the mechanisms of CRMO.MaterialsMicroarray data from the GSE133378 (12 CRMO and 148 matched normal tissue samples) data sets were downloaded from the Gene Expression Omnibus (GEO) database. DEGs were identified using the limma package in the R software. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were performed to further investigate the function of the identified DEGs.ResultsThis study identified a total of 1299 differentially expressed mRNAs, including1177 upregulated genes and 122 downregulated genes, between CRMO and matched normal tissue samples. GO analyses showed that DEGs were enriched in immune-related terms. KEGG pathway enrichment analyses showed that the DEGs were mainly related to oxidative phosphorylation, ribosome, and Parkinson disease. Eight modules were extracted from the gene expression network, including one module constituted with immune-related genes and one module constituted with ribosomal-related genes.ConclusionOxidative phosphorylation, ribosome, and Parkinson disease pathways were significantly associated with CRMO. The immune-related genes including IRF5, OAS3, and HLA-A, as well as numerous ribosomal-related genes, might be implicated in the pathogenesis of CRMO. The identification of these genes may contribute to the development of early diagnostic tools, prognostic markers, or therapeutic targets in CRMO.
| S-EPMC7888306 | biostudies-literature
Project description:We report a case of a 13-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) who developed severe arthritis in four different joints within the first year from the onset of the disease. Her multiple vertebrae lesions showed significant amelioration after a 2-month treatment with prednisolone. In parallel, the initial severe symmetrical arthritis of both knees showing overt synovitis and joint effusion, in the absence of lesions in the metaphyses of the femur or the tibia, responded remarkably well in intra-articular triamcinolone hexacetonide injections. However, upon discontinuation of prednisolone, the patient developed severe arthritis of her right ankle and the proximal interphalangeal joint of her right middle finger. Thus, prednisolone was reinitiated combined with methotrexate, and the patient went into remission, which persists one year after prednisolone tapering. The appearance of arthritis in both knees in the absence of bone lesions and the emergence of severe arthritis of the ankle after remission of spinal bone lesions suggest that CRMO and juvenile idiopathic arthritis may coexist and be causally related.
| S-EPMC3420544 | biostudies-literature
Project description:Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents. Microarray analysis of bone marrow macrophages from the CRMO murine model (cmo) determined that the Fblim1 ortholog is the most differentially expressed gene, downregulated over 20-fold in the cmo mouse. We sequenced FBLIM1 in 96 CRMO subjects and found a second proband with a novel frameshift mutation in exon 6 and a rare regulatory variant. In SaOS2 cells, overexpressing the regulatory mutation showed the flanking region acts as an enhancer, and the mutation ablates enhancer activity. Our data implicate FBLIM1 in the pathogenesis of sterile bone inflammation and our findings suggest CRMO is a disorder of chronic inflammation and imbalanced bone remodeling.
| S-EPMC5354242 | biostudies-literature
Project description:To explore how APOE functions in the mechanism of regulation of cholesterol metabolism during S. aureus osteomyelitis, we established S. aureus osteomyelitis models in WT mice and APOE knockout mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of bone marrow from mice mentioned above at day 7 after operation.
2023-07-09 | GSE227521 | GEO
Project description:We aimed to elucidate the mechanism of IL-27/ IL-27 receptor signaling effects on S. aureus osteomyelitis via gene expression studies.
2021-03-16 | GSE168896 | GEO