Disordered gut microbiota and alterations in metabolic patterns are associated with atrial fibrillation.
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ABSTRACT:
SUBMITTER: Zuo K
PROVIDER: S-EPMC6543127 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Project description:Atrial fibrillation (AF) has been shown to be associated with disordered gut microbiota (GM). The underlying factors governing persistent AF (psAF) are not well understood, and the association between AF duration and GM profiles remains to be characterized. Thus, the present study aimed at investigating the dysbiosis of GM in patients with short and long psAF duration and illuminating the relationship between the GM and psAF maintenance. Based on metagenomic sequencing and metabolomic analyses, we assessed the metabolic and GM signature in 12 patients with psAF of <12?months (Pers<12m), eight patients with psAF of >12?months (Pers>12m), and 20 controls. We found that the GM in patients with both Pers<12m and Pers>12m was significantly perturbed, with an elevated microbial diversity, distinct structure, and discrepant composition. Although Pers<12m and Pers>12m patients shared a large number of common bacteria with controls, including 84 genera and 404 species, certain bacteria were differently enriched at different AF durations. Furthermore, disturbance in gut microbial function and GM-linked metabolic alterations were detected in both the Pers<12m and Pers>12m groups. The connection of GM and metabolites with psAF is consistent with interaction and potential modulation of host metabolic pathways due to GM dysbiosis with AF persistence. Our results showed that patients of the Pers<12m and Pers>12m groups shared many common disordered GM and metabolic features, which might occur in early disease, while prolonged psAF duration was related to certain unique alterations. Preventative strategies targeting GM and microbial metabolites for early intervention to treat AF patients are highly warranted.IMPORTANCE Atrial fibrillation was associated with a disordered gut microbiota in previous research. However, the gut microbiota signature of patients at different stages of atrial fibrillation remains largely unknown. We sought to determine whether the shift in the gut microbiota and metabolic profiles occurs early and remains stable or develops gradually during atrial fibrillation. We found that patients with persistent atrial fibrillation of <12?months and persistent atrial fibrillation of >12?months shared most of the common features of gut microbiota dysbiosis. However, some distinctive and progressive alterations in the gut microbiota and metabolic structure, which may contribute to the progression of atrial fibrillation, were identified. The present study provides a comprehensive description of the dysbiotic gut microbiota and metabolic profiles in patients of short and long persistent atrial fibrillation, and our findings may help identify therapeutic strategies targeting the gut microbiota to treat atrial fibrillation at an early stage.
| S-EPMC6906738 | biostudies-literature
Project description:Little evidence has been reported in characterizing the serum alterations in metabolic patterns in atrial fibrillation (AF). We include the result of the global alterations that occur in the intestinal microbiota in a cohort of AF patients and matched controls based on a strategy of metabolomic analyses. Our findings characterize the disordered microbial metabolite profiles in AF.
2019-04-11 | ST001169 | MetabolomicsWorkbench
Project description:Little evidence has been reported in characterizing the fecal alterations in metabolic patterns in atrial fibrillation (AF). We include the result of the global alterations that occur in the intestinal microbiota in a cohort of AF patients and matched controls based on a strategy of metabolomic analyses. Our findings characterize the disordered microbial metabolite profiles in AF.
2019-04-10 | ST001168 | MetabolomicsWorkbench
Project description:Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF). However, little evidence has been reported in characterizing the specific changes in fecal microbiota in paroxysmal AF (PAF) and persistent AF (psAF). To provide a comprehensive understanding of GM dysbiosis in AF types, we assessed the GM signatures of 30 PAF patients, 20 psAF patients, and 50 non-AF controls based on metagenomic and metabolomic analyses. Compared with control subjects, similar changes of GM were identified in PAF and psAF patients, with elevated microbial diversity and similar alteration in the microbiota composition. PAF and psAF patients shared the majority of differential taxa compared with non-AF controls. Moreover, the similarity was also illuminated in microbial function and associated metabolic alterations. Additionally, minor disparity was observed in PAF compared with psAF. Several distinctive taxa between PAF and psAF were correlated with certain metabolites and atrial diameter, which might play a role in the pathogenesis of atrial remodeling. Our findings characterized the presence of many common features in GM shared by PAF and psAF, which occurred at the self-terminating PAF. Preventative and therapeutic measures targeting GM for early intervention to postpone the progression of AF are highly warranted.IMPORTANCE Atrial fibrillation has been identified to be associated with disordered gut microbiota. Notably, atrial fibrillation is a progressive disease and could be categorized as paroxysmal and persistent based on the duration of the episodes. The persistent atrial fibrillation patients are accompanied by higher risk of stroke and lower success rate of rhythm control. However, the microbial signatures of different categories of atrial fibrillation patients remain unknown. We sought to determine whether disordered gut microbiota occurs in the self-terminating PAF or intestinal flora develops dynamically during atrial fibrillation progression. We found that different types of atrial fibrillation show a limited degree of gut microbiota shift. Gut microbiota dysbiosis has already occurred in mild stages of atrial fibrillation, which might act as an early modulator of disease, and therefore may be regarded as a potential target to postpone atrial fibrillation progression.
| S-EPMC7082137 | biostudies-literature
Project description:The gut microbiota has a known complex association with atrial fibrillation (AF) progression, but the association of gut viruses with AF is undefined. Metagenomic data in a cohort of 50 AF patients and 50 matched controls were examined to profile the gut viral signals and determine their associations with intestinal bacteria and the AF phenotype. The gut viral alterations were examined, and the marked elevation of viral diversity, including increased Simpson, Shannon, and Pielou index, was revealed in AF patients. The specific alteration of the intestinal viral population, such as overgrowth of Streptococcus virus DT1 and Pseudomonas phage, as well as imbalanced gut viral function, dominated by integral component of the membrane, and metal ion binding were detected in AF patients. Moreover, regarding co-occurrence networks connecting viruses and bacterial organisms, increasingly disordered virus-bacteria linkages were seen in AF cases with severe AF progression. Notably, the associations of Synechococcus phage S-SM1 and Cronobacter phage CR5 with bacterial species were very tight in control individuals but markedly dampened in AF cases. Furthermore, the viral score built by the selected discriminative taxa between AF cases with or without recurrence after ablation was still significantly associated with recurrence (HR = 2.959, P = 0.0085), with a survival AUC of 0.878. We demonstrated for the first time that gut viral signatures are associated with AF, and suppressed viral-bacterial associations in AF suggest the gut virus might participate in AF progression, which has a potential value in predicting ablation outcomes.
| S-EPMC9467389 | biostudies-literature
Project description:Disordered gut microbiota (GM) as the co-contributor of atrial fibrillation (AF) and hypertension (HTN) might be associated with AF risk in HTN. This study aimed to explore the altered GM community and metabolic patterns between 27 HTN patients with AF (HTN-AF) and 27 non-AF HTN patients through fecal metagenomic and serum metabolomic analysis. Compared to non-AF HTN patients, significant microbial alterations (p = 0.004), including increased microbial diversity (p < 0.05), shifted enterotype dominated by Prevotella to Bacteroides, and abundant disease-linked genera Ruminococcus, Streptococcus, Veillonella, Dorea, and Enterococcus, were observed in HTN-AF patients. A species-based random forest prediction model was associated with the risk of AF occurrence in HTN patients. Furthermore, GM metabolic profiles dramatically differed between HTN and HTN-AF patients, especially the imbalance of saturated and unsaturated fatty acids. In HTN-AF patients, circulating palmitic acid and arachidonic acid levels were significantly elevated, while the levels of tetracosahexaenoic acid, oleic acid, linoleic acid, and stearic acid were decreased (p < 0.001, VIP > 1), mediating 85.99% of gut microbial indirect effects on AF (p < 0.001). Thus, our findings preliminarily indicated that exacerbated dysbiosis of GM and relevant metabolites was associated with high AF susceptibility and might be a potential target for AF prediction and prevention in HTN.
| S-EPMC9599445 | biostudies-literature
Project description:Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk factors, including heart failure, hypertension, obesity, and coronary artery disease. We also discuss the potential anti-arrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.
| S-EPMC9400433 | biostudies-literature
Project description:BackgroundThe imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive.MethodsIn this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package.ResultsThe gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P < 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P < 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P < 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P < 0.05).ConclusionsOur study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.
| S-EPMC10080059 | biostudies-literature
Project description:Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson's disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson's disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson's disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson's disease.IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson's disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson's disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson's disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.
| S-EPMC7498685 | biostudies-literature
Project description:In recent decades, increasing evidence has strongly suggested that gut microbiota play an important role in many intestinal diseases including inflammatory bowel disease (IBD) and colorectal cancer (CRC). The composition of gut microbiota is thought to be largely shaped by interspecies competition for available resources and also by cooperative interactions. However, to what extent the changes could be attributed to external factors such as diet of choice and internal factors including mutual relationships among gut microbiota, respectively, are yet to be elucidated. Due to the advances of high-throughput sequencing technologies, flood of (meta)-genome sequence information and high-throughput biological data are available for gut microbiota and their association with intestinal diseases, making it easier to gain understanding of microbial physiology at the systems level. In addition, the newly developed genome-scale metabolic models that cover significant proportion of known gut microbes enable researchers to analyze and simulate the system-level metabolic response in response to different stimuli in the gut, providing deeper biological insights. Using metabolic interaction network based on pair-wise metabolic dependencies, we found the same interaction pattern in two IBD datasets and one CRC datasets. We report here for the first time that the growth of significantly enriched bacteria in IBD and CRC patients could be boosted by other bacteria including other significantly increased ones. Conversely, the growth of probiotics could be strongly inhibited from other species, including other probiotics. Therefore, it is very important to take the mutual interaction of probiotics into consideration when developing probiotics or "microbial based therapies." Together, our metabolic interaction network analysis can predict majority of the changes in terms of the changed directions in the gut microbiota during enteropathogenesis. Our results thus revealed unappreciated interaction patterns between species could underlie alterations in gut microbiota during enteropathogenesis, and between probiotics and other microbes. Our methods provided a new framework for studying interactions in gut microbiome and their roles in health and disease.
| S-EPMC6558107 | biostudies-literature