scholarly journals Exploration of Crucial Mediators for Carotid Atherosclerosis Pathogenesis Through Integration of Microbiome, Metabolome, and Transcriptome

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Ji ◽  
Siliang Chen ◽  
Guangchao Gu ◽  
Jiawei Zhou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Theoretical Basis ◽  
Carotid Atherosclerosis ◽  
Fold Change ◽  
Plasma Metabolites ◽  
Healthy Controls ◽  
Metabolomic Analysis ◽  
16S Ribosomal Dna ◽  
Gene Regulatory ◽  
Spearman’S Correlation

BackgroundCarotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.Materials and MethodsWe utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log2(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.ResultsA total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log2(fold change)|. Furthermore, FABP4 was positively associated with Acidaminococcus and had the highest Spearman’s correlation coefficient and the most significant p-value among the microbiota–DEG pairs.ConclusionIn this study, we investigated the potential “microbiota–metabolite–gene” regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.

scholarly journals Children Developing Celiac Disease Have a Distinct and Proinflammatory Gut Microbiota in the First 5 Years of Life

2020 ◽  
Author(s):  
Qian Huang ◽  
Yi Yang ◽  
Vladimir Tolstikov ◽  
Michael A. Kiebish ◽  
Jonas F Ludvigsson ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Plasma Metabolites ◽  
List Type ◽  
Healthy Controls ◽  
Microbiota Composition ◽  
Immune Mediated ◽  
Gut Microbiota Composition

ABSTRACTObjectiveCeliac disease (CD) is an immune-mediated disease characterized by small intestinal inflammation. CD is associated with HLA-DQ2 and HLA-DQ8 haplotypes, however, genetics alone cannot explain the increasing incidence rates. The main goal of this study was to determine the role of the gut microbiota in CD pathogenesis in the first five years of life.DesignWe conducted a longitudinal study focusing on three developmental phases of the gut microbiota (ages 1, 2.5 and 5 years). The fecal samples were obtained from 16 children who developed CD and 16 matched controls. We used 16S sequencing combined with functional analysis, flow cytometry, immunoglobulin A (IgA) sequencing (IgA-seq), and plasma metabolomics to determine a microbial link to CD pathogenesis.ResultsWe identified a distinct gut microbiota composition in CD progressors (CDP, children who developed CD during or after their gut microbiota were sampled) in each developmental phase. Pathogenesis and inflammation-related microbial pathways were enriched in CDP. Moreover, they had significantly more IgA coated bacteria and the IgA targets were significantly different compared to controls. Proinflammatory and pathogenesis-related metabolic pathways were enriched in CDP. Further, we identified inflammatory metabolites, particularly microbiota-derived taurodeoxycholic acid (TDCA) as increased in CDP.ConclusionOur study defines an inflammatory gut microbiota for the CDP including its composition, function, IgA response and related plasma metabolites. The inflammatory nature of CD gut microbiota during development is potentially related to the onset of the disease. Targeting inflammatory bacteria in this critical window could affect the pathogenesis and prognosis of CD.Significance of this studyWhat is already known on this subject?Celiac Disease (CD) is a gluten induced immune-mediated disease in genetically predisposed individuals.CD incidence is increasing worldwide which genetics alone cannot explain. Previous studies have shown that the gut microbiota of CD patients differ from that of healthy populations. However, the role of the microbiome in CD pathogenesis and its role in chronic inflammation is yet be established.What are the new findings?In a prospective longitudinal study in children using samples representing all three phases of gut microbiota development (ages 1, 2.5 and 5), we identified significant differences in the composition and function of gut microbiota at each phase. Pathogenesis and inflammation-related functions are enriched in the gut microbiome of CD progressors.We applied IgA-sequencing to identify inflammatory bacteria in both healthy subjects and CD progressors. Flow Cytometry analysis identified more IgA coated bacteria at ages 1 and 5 in CD progressors, indicating an early inflammatory response. CD bacterial IgA targets also differed significantly from healthy controls.We analyzed plasma metabolites obtained at age 5. The CD plasma metabolome was significantly different from healthy controls. Particularly, proinflammatory plasma metabolites, including microbiota-derived taurodeoxycholic acid (TDCA) and isobutyryl-L-carnitine, were increased two-fold in CD progressors.How might it impact clinical practice in the foreseeable future?Our results establish a link between gut microbiota composition and chronic inflammation in CD during child development. The highly IgA-coated bacteria identified in IgA sequencing and inflammatory bacteria potentially contribute to CD pathogenesis. Targeting these bacteria in the early stages of CD development could be a preventative tool.TDCA is a microbiota-derived proinflammatory metabolite increased two-fold in CD progressors. Increased TDCA levels may be used as a predictive/diagnostic tool in genetically predisposed subjects. Moreover, targeting TDCA-producing bacteria (e.g., Clostridium XIVa species) could potentially help to control the intestinal inflammation in CD.Developing anti-inflammatory probiotics/prebiotics might be viable therapeutics for altering microbiota composition in children genetically predisposed for CD. These microbes/compounds may also complement a gluten-free diet in patients that continue to experience persistent CD symptoms.

scholarly journals DNA Methylation Profiling for the Diagnosis and Prognosis of Patients with Nontuberculous Mycobacterium Lung Disease

2021 ◽  
Vol 43 (2) ◽  
pp. 501-512
Author(s):  
Jee Youn Oh ◽  
Young Kyung Ko ◽  
Jeong-An Gim
Keyword(s):  
Dna Methylation ◽  
Lung Disease ◽  
Poor Prognosis ◽  
Wnt Signaling Pathway ◽  
Fold Change ◽  
Nontuberculous Mycobacterium ◽  
Healthy Controls ◽  
Log2 Fold Change ◽  
Diagnosis And Prognosis ◽  
Ntm Lung Disease

The incidence of nontuberculous Mycobacterium (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis (n = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the “pathfinder” package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and p < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and p < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. TGFBr1 was significantly less methylated, whereas HLA-DR1 and HLA-DR5 were more methylated in patients with poor prognosis (compared to those with good prognosis). LRP5, E2F1, and ADCY3 were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1-cell differentiation, such as TGFBr1 and HLA-DR, may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.

scholarly journals Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenhai Gong ◽  
Yinglin Feng ◽  
Yunong Zeng ◽  
Huanrui Zhang ◽  
Meiping Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Gene Sequencing ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Metabolomic Analysis ◽  
Rrna Gene Sequencing ◽  
And Oxidative Stress

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

scholarly journals Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Shi ◽  
Di Zhao ◽  
Fan Zhao ◽  
Chong Wang ◽  
Galia Zamaratskaia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Branched Chain Fatty Acids ◽  
Tryptophan Metabolites ◽  
Branched Chain ◽  
Spearman’S Correlation ◽  
Gut Microbiota Composition ◽  
Chain Fatty Acids

AbstractThis study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.

scholarly journals Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Chih-Yu Yang ◽  
Ting-Wen Chen ◽  
Wan-Lun Lu ◽  
Shih-Shin Liang ◽  
Hsien-Da Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Statistical Significance ◽  
Additional Treatment ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Healthy Controls ◽  
Gut Dysbiosis ◽  
Novel Concept

Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

scholarly journals Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

2021 ◽  
Author(s):  
Natthaya Chuaypen ◽  
Thananya Jinato ◽  
Anchalee Avihingsanon ◽  
Sakkarin Chirapongsathorn ◽  
Supapon Cheevadhanarak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gut Microbiota ◽  
Alpha Diversity ◽  
Healthy Controls ◽  
Direct Acting Antivirals ◽  
Microbial Dysbiosis ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

scholarly journals Dysbiosis characteristics of gut microbiota in cerebral infarction patients

2020 ◽  
Vol 11 (1) ◽  
pp. 124-133
Author(s):  
Hao Li ◽  
Xiaohui Zhang ◽  
Dengdeng Pan ◽  
Yongqiang Liu ◽  
Xuebing Yan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cerebral Infarction ◽  
Operating Characteristic ◽  
National Institutes Of Health ◽  
Diagnostic Model ◽  
Healthy Controls ◽  
Characteristic Analysis ◽  
Rrna Sequencing ◽  
Stool Samples ◽  
Microbiota Diversity

AbstractObjectiveThe aim of this study is to investigate the dysbiosis characteristics of gut microbiota in patients with cerebral infarction (CI) and its clinical implications.MethodsStool samples were collected from 79 CI patients and 98 healthy controls and subjected to 16S rRNA sequencing to identify stool microbes. Altered compositions and functions of gut microbiota in CI and its correlation with clinical features were investigated. Random forest and receiver operating characteristic analysis were used to develop a diagnostic model.ResultsMicrobiota diversity and structure between CI patients and healthy controls were overall similar. However, butyrate-producing bacteria (BPB) were significantly reduced in CI patients, while lactic acid bacteria (LAB) were increased. Genetically, BPB-related functional genes were reduced in CI patients, whereas LAB-related genes were enhanced. The interbacterial correlations among BPB in CI patients were less prominent than those in healthy controls. Clinically, BPB was negatively associated with the National Institutes of Health Stroke Scale (NIHSS), while LAB was positively correlated with NIHSS. Both BPB and LAB played leading roles in the diagnostic model based on 47 bacteria.ConclusionsThe abundance and functions of BPB in CI patients were significantly decreased, while LAB were increased. Both BPB and LAB displayed promising potential in the assessment and diagnosis of CI.

scholarly journals Effects of Transanal Irrigation on Gut Microbiota in Pediatric Patients with Spina Bifida

2021 ◽  
Vol 10 (2) ◽  
pp. 224
Author(s):  
Akira Furuta ◽  
Yasuyuki Suzuki ◽  
Ryosuke Takahashi ◽  
Birte Petersen Jakobsen ◽  
Takahiro Kimura ◽  
...  
Keyword(s):  
Spina Bifida ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Pediatric Patients ◽  
Host Immune System ◽  
Healthy Controls ◽  
Transanal Irrigation ◽  
Rrna Sequencing ◽  
Before And After ◽  
Neurogenic Bowel

Recent studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in constipated patients. The aim of this study was to investigate the changes in gut microbiota after transanal irrigation (TAI) in patients with spina bifida (SB). A questionnaire on neurogenic bowel disfunction (NBD), Bristol scale, and gut microbiota using 16S rRNA sequencing were completed in 16 SB patients and 10 healthy controls aged 6–17 years. Then, 11 of 16 SB patients with moderate to severe NBD scores received TAI for 3 months. Changes in urine cultures were also examined before and after the TAI treatments. In addition, correlation of gut microbiota and Bristol scale was analyzed. Significantly decreased abundance in Faecalibacterium, Blautia and Roseburia, and significantly increased abundance in Bacteroides and Roseburia were observed in the SB patients compared with controls and after TAI, respectively. The abundance of Roseburia was significantly correlated positively with Bristol scale. Urinary tract infection tended to decrease from 82% to 55% after TAI (p = 0.082) despite persistent fecal incontinence. Butyrate-producing bacteria such as Roseburia play a regulatory role in the intestinal motility and host immune system, suggesting the effects of TAI on gut microbiota.

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