Proteus mirabilis Targets Atherosclerosis Plaques in Human Coronary Arteries via DC-SIGN (CD209)

Xue, Ying; Li, Qiao; Park, Chae Gyu; Klena, John D.; Anisimov, Andrey P.; Sun, Ziyong; Wei, Xiang; Chen, Tie

doi:10.3389/fimmu.2020.579010

Cited by 13 publications

(10 citation statements)

References 102 publications

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“…46 A recent experimental study found that the Proteus mirabilis may interact with atherosclerotic plaques in human coronary arteries via dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin, and higher abundance of Proteus mirabilis was found in the hearts from atherosclerotic mice compared with control mice. 47 These previous results are in line with our findings, and all suggest a potential involvement of Proteus in the atherosclerotic plaque formation. Moreover, we found similar but relative weaker associations of gut Proteus , compared with gut Fusobacterium , with microbial functions in the lipid metabolism and alternations of host plasma lipid profiles (eg, lysophosphatidylcholines, lysophosphatidylethanolamines, and diglycerides) associated with carotid artery atherosclerosis, though the underlying mechanisms warrants further investigation.…”

Section: Discussionsupporting

confidence: 92%

Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection

Wang

Peters

Usyk

et al. 2022

ATVB

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Background: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. Methods: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. Results: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus , were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09–1.64] and 1.24 [1.02–1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. Conclusions: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

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Section: Discussionsupporting

confidence: 92%

Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection

Wang

Peters

Usyk

et al. 2022

ATVB

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“…According to previous studies, the genus of Proteobacteria were involved in the formation of atherosclerosis. For instance, Proteus vulgaris was found to be present in the plaques and intestines of the same individual [ 52 ], Proteus mirabilis can interact with atherosclerosis plaques in human coronary arteries via specific molecular to exacerbate the progression of disease [ 53 ]. In addition, the abundance of Proteus in the blood of cardiovascular disease patients was observed to be increased compared with healthy individuals [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide association study identified candidate genes associated with gut microbiota

et al. 2021

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Background Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets. Results TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus Bifidobacterium in transverse colon (PPERM.ANL = 1.68 × 10–3) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (PPERM.ANL = 5.69 × 10–3). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for Streptococcus (PIP = 0.685) in sigmoid colon, ANO7 for Erysipelotrichaceae (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10–4), KEGG_RENIN_ANGIOTENSIN_SYSTEM for Anaerostipes (FDR P = 3.16 × 10–2). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of Proteobacteria was related to atherosclerosis, and FUT2 for Bifidobacterium was associated with Crohn’s disease. Conclusions Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases.

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“…The expression of CCL18 [109], SLAMF7 [110], GPR174 [111], CCR4 [112], POU4F2 [113]. CCR2 [114], IL2RB [115], CCL4 [116], CCL24 [117], FASLG (Fas ligand) [118], CD24 [119], TDGF1 [120], CD28 [121], IL7R [122], CYP11B1 [123], CCL5 [124], CCL3 [125], LTF (lactotransferrin) [126], GPNMB (glycoprotein nmb) [127], CD209 [128], IL2RG [129], CHIT1 [130], TAB2 [131], CD163 [132], ALOX15B [133], NMRK2 [134], HGF (hepatocyte growth factor) [135], TRPM8 [136], DIO3 [137], SIGLEC1 [138], TTR (transthyretin) [139], IL24 [140], F13A1 [141], IL9 [142], VEGFA (vascular endothelial growth factor A) [143], RASAL1 [144], ADM (adrenomedullin) [145], ANGPTL4 [146], CHI3L1 [147], LDB3 [148], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [149], HES6 [150], CMTM5 [151], PLXNB3 [152], KLK8 [153], CDKN1C [154], INSIG1 [155], GREM1 [156], ATF3 [157], HK2 [158], MCAM (melanoma cell adhesion molecule) [159], SEMA4D [160], GLUL (glutamate-ammonia ligase) [161], S1PR5 [162], FN3K [163], MEIS1 [164], ADAMTS4 [165], BIN1 [166], BMP2 [167], LMNA (lamin A/C) [168], ERBB3 [169], DLL1 [170], THBS2 [171], GADD45B [172], MYH6 [173]. PNPLA3 [174], ACTN2 [175], MMP15 [176], SVEP1 [177], CPB2 [178], DYSF (dysferlin) [179], ADAMTSL2 [180], NINJ2 [181], LRP2 [106], PHLDA3 […”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Multiple sclerosis (MS) is the main reason for disability caused by autoimmunity. However, effective biomarkers for MS have not been identified. This study explored the molecular mechanisms and potential therapeutic targets for MS occurrence and progression using bioinformatics and next generation sequencing (NGS) data analysis. NGS data GSE138614, including patients with MS and 25 normal control samples, were obtained from Gene Expression Omnibus (GEO) database Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. Protein–protein interaction (PPI) network and module analyses were performed based on the DEGs. MiRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were built by Cytoscape to predict the underlying microRNAs (miRNAs) and transcription factors (TFs) associated with hub genes. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. A total of 959 DEGs (479 up regulated genes and 480 down regulated genes) were detected. The GO terms and pathways of DEGs involve immune system process, developmental process, immune system and regulation of cholesterol biosynthesis by SREBP (SREBF). The network analysis revealed that hub genes include LCK, PYHIN1, SLAMF1, DOK2, TAB2, CFTR, RHOB, LMNA, EGLN3 and ERBB3 might be involved in the development of MS. The present investigation illustrates a characteristic gene profile in MS, which might contribute to the interpretation of the progression of MS and provide novel biomarkers and therapeutic targets for MS.

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Proteus mirabilis Targets Atherosclerosis Plaques in Human Coronary Arteries via DC-SIGN (CD209)

Cited by 13 publications

References 102 publications

Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection

Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection

Transcriptome-wide association study identified candidate genes associated with gut microbiota

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

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