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Bidirectional effects of oral anticoagulants on gut microbiota in patients with atrial fibrillation.Frontiers in Cellular and Infection... 2023The 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...
BACKGROUND
The 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.
METHODS
In 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.
RESULTS
The gut microbiota differed between the AF-OAC and AF groups. The abundance of and decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as . In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus but increased certain potential pathogenic taxa, such as genera , , and . The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that , , and were more abundant in the anticoagulated bleeding AF patients, and 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 ( < 0.05). was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score ( < 0.05), and the OACs-enriched species ( and ) was positively correlated with the prothrombin time (PT) ( < 0.05). and were negatively associated with bleeding events ( < 0.05).
CONCLUSIONS
Our 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 and might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.
Topics: Humans; Atrial Fibrillation; Gastrointestinal Microbiome; Phylogeny; RNA, Ribosomal, 16S; Stroke; Risk Factors; Anticoagulants; Hemorrhage; Administration, Oral; Risk Assessment
PubMed: 37033478
DOI: 10.3389/fcimb.2023.1038472 -
Frontiers in Cellular and Infection... 2022Although the gut microbiota may be involved in obesity onset and progression, the exact association of the gut microbiota in metabolically healthy obesity (MHO) remains...
BACKGROUND
Although the gut microbiota may be involved in obesity onset and progression, the exact association of the gut microbiota in metabolically healthy obesity (MHO) remains largely unknown.
METHODS
An integrated paired-sample metagenomic analysis was conducted to investigate the gut microbial network and biomarkers of microbial species from the MHO and healthy non-obese subjects in the GMrepo database. Further explorations were performed in the MHO mice model using a multiomics analysis to detect changes in the composition and function of the intestinal microbiome and associated metabolites.
RESULTS
In the human study, 314 matched metagenomic data were qualified for the final analysis. We identified seven significantly changed species possibly involved in MHO pathogenesis (MHO-enriched: , ; MHO-depleted: , , ; ; ). In the murine study, we found 79 significantly-changed species which may have possible associations with the MHO phenotype. The depletion of was commonly recognized in the human and murine MHO phenotype. Consistent with the metagenomic data, liquid chromatography-mass spectrometry (LC/MS) revealed significantly changed gut metabolites, which may promote MHO pathogenesis by altering the amino acids and lipid metabolic pathways. In the microbe-metabolites interaction analysis, we identified certain fatty acids (Dodecanedioic acid, Arachidic Acid, Mevalonic acid, etc.) that were significantly correlated with the MHO-enriched or depleted species.
CONCLUSION
This study provides insights into identifying specific microbes and metabolites that may involve in the development of obesity without metabolic disorders. Future modalities for MHO intervention may be further validated by targeting these bacteria and metabolites.
Topics: Humans; Mice; Animals; Gastrointestinal Microbiome; Obesity, Metabolically Benign; Obesity; Metagenomics
PubMed: 36389176
DOI: 10.3389/fcimb.2022.1012028 -
NPJ Biofilms and Microbiomes Nov 2023Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota....
Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota. However, the underlying mechanisms are not fully understood. Here we used high-fat diet (HFD)-induced laying hen model of MAFLD to investigate the effect of inulin on ameliorating MAFLD and found that the inulin-enriched Megamonas genus was inversely correlated with hepatic steatosis-related parameters. Oral administration of a newly isolated commensal bacterium by culturomics, M. funiformis CML154, to HFD-fed hens and mice ameliorated MAFLD, changed liver gene expression profiles, and increased intestinal propionate concentration. Further evidence demonstrated that the anti-MAFLD effect of M. funiformis CML154 is attributed to propionate-mediated activation of the APN-AMPK-PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. These findings establish the causal relationships among inulin, M. funiformis, and MAFLD, and suggest that M. funiformis CML154 is a probiotic candidate for preventative or therapeutic intervention of MAFLD.
Topics: Animals; Female; Mice; Propionates; Inulin; Chickens; Non-alcoholic Fatty Liver Disease
PubMed: 37925493
DOI: 10.1038/s41522-023-00451-y -
Scientific Reports Nov 2023Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant... (Clinical Trial)
Clinical Trial
Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).
Topics: Child; Humans; Autism Spectrum Disorder; Constipation; East Asian People; Fatty Acids, Volatile; Gastrointestinal Microbiome; Lactobacillales; Propionates; RNA, Ribosomal, 16S; Veillonellaceae
PubMed: 37925571
DOI: 10.1038/s41598-023-46566-2 -
International Journal of Molecular... Jul 2023The composition of the gut microbiome is altered in patients with chronic kidney disease (CKD). Dysbiosis leads to decreased levels of stool organic acids (OAs) and...
The composition of the gut microbiome is altered in patients with chronic kidney disease (CKD). Dysbiosis leads to decreased levels of stool organic acids (OAs) and systemic inflammation, followed by accumulation of uremic toxins (UTs) and the development of end-stage kidney disease (ESKD). We assessed the relationship between the microbiome and UT levels or the development of ESKD by comparing patients undergoing hemodialysis (HD) and those with normal renal function (NRF). This cross-sectional study recruited 41 patients undergoing HD and 38 sex- and age-matched patients with NRF, and gut microbiome, levels of plasma UTs, inflammatory markers, and stool OAs were compared. The indices of beta-diversity differed significantly between patients with NRF and those undergoing HD, and between patients undergoing HD with and without type 2 diabetes. The levels of stool total OA, inflammatory markers, and UTs differed significantly between the patients with NRF and those undergoing HD. The combined main effects of type 2 diabetes and kidney function status were accumulation of indoxyl sulfate and p-cresyl sulfate. The relative abundances of and were associated with development of ESKD and with the levels of UTs, even after adjustment for factors associated with the progression of ESKD. The present study indicates that the gut environment differs between patients with NRF and those undergoing HD and between patients undergoing HD with and without type 2 diabetes. Moreover, ESKD patients with diabetes accumulate more UTs derived from the gut microbiome, which might be associated with cardio-renal diseases and poor prognosis.
Topics: Humans; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Microbiota
PubMed: 37511232
DOI: 10.3390/ijms241411456 -
Frontiers in Cellular and Infection... 2022To better understand the alterations in gut microbiota and metabolic pathways in children with focal epilepsy, and to further investigate the changes in the related gut...
OBJECTIVE
To better understand the alterations in gut microbiota and metabolic pathways in children with focal epilepsy, and to further investigate the changes in the related gut microbiota and metabolic pathways in these children before and after treatment.
METHODS
Ten patients with newly diagnosed focal epilepsy in Hunan Children's Hospital from April, 2020 to October, 2020 were recruited into the case group. The case group was further divided into a pre-treatment subgroup and a post-treatment subgroup. Additionally, 14 healthy children of the same age were recruited into a control group. The microbial communities were analyzed using 16s rDNA sequencing data. Metastas and LEfSe were used to identify different bacteria between and within groups. The Kyoto Encyclopedia of Genes and Genomes database was used to KEGG enrichment analysis.
RESULTS
There were significant differences in α diversity among the pre-treatment, post-treatment, and control groups. Besides, the differences in gut microbiota composition in 3 groups were identified by principal co-ordinates analysis (PCoA), which showed a similar composition of the pre-treatment and post-treatment subgroups. At the phyla level, the relative abundance of in the pre-treatment subgroup was significantly higher than that in the control group, which decreased significantly after 3 months of treatment and showed no significant difference between the control group. In terms of the genus level, , , , and were enriched in the pre-treatment subgroup, while and were enriched in the control group. The relative abundance of , , , and was reduced significantly after a three-month treatment. Despite some genera remaining significantly different between the post-treatment subgroup and control group, the number of significantly different genera decreased from 9 to 4 through treatment. Notably, we found that the carbohydrate metabolism, especially succinate, was related to focal epilepsy.
CONCLUSION
Children with focal epilepsy compared with healthy controls were associated with the statistically significant differences in the gut microbiota and carbohydrate metabolism. The differences were reduced and the carbohydrate metabolism improved after effective treatment. Our research may provide new directions for understanding the role of gut microbiota in the pathogenesis of focal epilepsy and better alternative treatments.
Topics: Humans; Child; Gastrointestinal Microbiome; Bacteria; Microbiota; Actinobacteria; Epilepsies, Partial
PubMed: 36405958
DOI: 10.3389/fcimb.2022.965471 -
Frontiers in Microbiology 2022The gut microbiota undergoes dynamic changes during pregnancy. The gut microbial and metabolic networks observed in pregnant women have not been systematically analyzed....
The gut microbiota undergoes dynamic changes during pregnancy. The gut microbial and metabolic networks observed in pregnant women have not been systematically analyzed. The primary purpose of this study was to explore the alterations in the gut microbiota and metabolism during late pregnancy and investigate the associations between the gut microbiota and metabolism. A total of thirty healthy pregnant women were followed from 30 to 32 weeks of gestation to full term. Fecal samples were collected for microbiome analysis and untargeted metabolomic analysis. The characteristics of the gut microbiota were evaluated by 16S ribosomal RNA gene sequencing of the V3-V4 regions. The plasma samples were used for untargeted metabolomic analysis with liquid chromatography-tandem mass spectrometry. The interplay between the gut microbiota and metabolism was analyzed further by bioinformatics approaches. We found that the relative abundances of and were higher at full term, whereas that of was lower. The correlation network of the gut microbiota tended to exhibit weaker connections from 32 weeks of gestation to the antepartum timepoint. Changes in the gut microbiota during late pregnancy were correlated with the absorbance and metabolism of microbiota-associated metabolites, such as fatty acids and free amino acids, thereby generating a unique metabolic system for the growth of the fetus. Decreasing the concentration of specific metabolites in plasma and increasing the levels of palmitic acid and 20-hydroxyarachidonic acid may enhance the transformation of a proinflammatory immune state as pregnancy progresses.
PubMed: 36569048
DOI: 10.3389/fmicb.2022.1059227 -
Scientific Reports Jun 2021This 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...
This 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.
Topics: Adolescent; Adult; Animals; Bacteria; Chickens; Diet; Fatty Acids, Volatile; Feces; Feeding Behavior; Gastrointestinal Microbiome; Humans; Male; Meat; Pork Meat; RNA, Ribosomal, 16S; Swine; Tryptophan; Young Adult
PubMed: 34099832
DOI: 10.1038/s41598-021-91429-3 -
Frontiers in Cellular and Infection... 2022There is a growing body of evidence highlighting the significant role of gut microbiota in various pathologies. We performed a systematic review to review the different... (Review)
Review
There is a growing body of evidence highlighting the significant role of gut microbiota in various pathologies. We performed a systematic review to review the different microbiota involved in neuropsychiatric diseases. 50 studies (23 studies for autism spectrum disorders, 18 for major depression, and 9 for schizophrenia), representing 2,137 patients and 2,844 controls. Concerning the microbiota, the genera were the ones detected with the most frequent variation of their relatives abundance. We also assess the overlap between the different pathologies. This study provides new insights into the complex relationship between the brain and the gut and the implications in neuropsychiatric pathologies. The identification of unique signatures in neuropsychiatric diseases suggests new possibilities in targeted anti or probiotic treatment.
Topics: Autism Spectrum Disorder; Brain; Gastrointestinal Microbiome; Humans; Microbiota; Probiotics
PubMed: 35360098
DOI: 10.3389/fcimb.2022.831666 -
Microbiome Oct 2023Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an...
BACKGROUND
Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota.
RESULTS
Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin.
CONCLUSIONS
Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract.
Topics: Dogs; Humans; Animals; Dermatitis, Atopic; Dysbiosis; Quality of Life; Microbiota; Bacteria; DNA, Mitochondrial
PubMed: 37864204
DOI: 10.1186/s40168-023-01671-2