Dataset Information

Gut Microbiome Alterations in Patients With Carotid Atherosclerosis.

ABSTRACT: Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima-media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut-brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, Bacteroides eggerthii, Escherichia coli, and Klebsiella pneumoniae were the most abundant species in the CAS group, whereas Parabacteroides unclassified, Prevotella copri, Bacteroides sp 3_1_19, and Haemophilus parainfluenzae were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.

SUBMITTER: Chen J

PROVIDER: S-EPMC8639581 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.

Project description:Dysbiosis in the gut microbiome has been implicated in several diseases including auto-immune diseases, inflammatory diseases, cancers and mental disorders. Keratitis is an inflammatory disease of the eye significantly contributing to corneal blindness in the developing world. It would be worthwhile to investigate the possibility of dysbiosis in the gut microbiome being associated with Keratitis. Here, we have analyzed fungal and bacterial populations in stool samples through high-throughput sequencing of the ITS2 region for fungi and V3-V4 region of 16S rRNA gene for bacteria in healthy controls (HC, n = 31) and patients with fungal keratitis (FK, n = 32). Candida albicans (2 OTUs), Aspergillus (1 OTU) and 3 other denovo-OTUs were enriched in FK samples and an unclassified denovo-OTU was enriched in HC samples. However, the overall abundances of these 'discriminatory' OTUs were very low (< 0.001%) and not indicative of significant dysbiosis in the fungal community inhabiting the gut of FK patients. In contrast, the gut bacterial richness and diversity in FK patients was significantly decreased when compared to HC. 52 OTUs were significantly enriched in HC samples whereas only 5 OTUs in FK. The OTUs prominently enriched in HC were identified as Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Lachnospira, Mitsuokella multacida, Bacteroides plebeius, Megasphaera and Lachnospiraceae. In FK samples, 5 OTUs affiliated to Bacteroides fragilis, Dorea, Treponema, Fusobacteriaceae, and Acidimicrobiales were significantly higher in abundance. The functional implications are that Faecalibacterium prausnitzii, an anti-inflammatory bacterium and Megasphaera, Mitsuokella multacida and Lachnospira are butyrate producers, which were enriched in HC patients, whereas Treponema and Bacteroides fragilis, which are pathogenic were abundant in FK patients, playing a potential pro-inflammatory role. Heatmap, PCoA plots and functional profiles further confirm the distinct patterns of gut bacterial composition in FK and HC samples. Our study demonstrates dysbiosis in the gut bacterial microbiomes of FK patients compared to HC. Further, based on inferred functions, it appears that dysbiosis in the gut of FK subjects is strongly associated with the disease phenotype with decrease in abundance of beneficial bacteria and increase in abundance of pro-inflammatory and pathogenic bacteria.

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Gut Microbiome Alterations in Patients With Carotid Atherosclerosis.

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