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Frontiers in Microbiology 2023Recent studies have suggested that the composition of gut microbiota (GM) may change after intracerebral hemorrhage. However, the causal inference of GM and hemorrhagic...
BACKGROUND
Recent studies have suggested that the composition of gut microbiota (GM) may change after intracerebral hemorrhage. However, the causal inference of GM and hemorrhagic stroke is unknown. Mendelian Randomization (MR) is an effective research method that removes confounding factors and investigates the causal relationship between exposure and outcome. This study intends to explore the causal relationship between GM and hemorrhagic stroke with the help of MR.
METHODS
Univariable and multivariable MR analyses were performed using summary statistics of the GM ( = 18,340) in the MiBioGen consortium vs. the FinnGen consortium R9 summary statistics (intracerebral hemorrhage, subarachnoid hemorrhage, and nontraumatic intracranial hemorrhage). Causal associations between gut microbiota and hemorrhagic stroke were analyzed using inverse variance weighted, MR-Egger regression, weighted median, weighted mode, simple mode, and MR-PRESSO. Cochran's statistic, MR-Egger regression, and leave-one-out analysis were used to test for multiplicity and heterogeneity of instrumental variables. Separate reverse MR analyses were performed for microbiota found to be causally associated with hemorrhagic stroke in the forward MR analysis. Also, multivariate MR analyses were conducted after incorporating common confounders.
RESULTS
Based on the results of univariable and multivariate MR analyses, (OR, 0.80; 95%CI, 0.66-0.97; = 0.025) had a protective effect against hemorrhagic stroke, while (OR, 0.81; 95%CI, 0.67-0.99; = 0.039) had a potential protective effect. Furthermore, (OR, 1.77; 95%CI, 1.27-2.46; = 0.001), (OR, 1.24; 95%CI, 1.05-1.48; = 0.013) and (OR, 1.28; 95%CI, 1.01-1.62; = 0.041) acted as potential risk factors for hemorrhagic stroke. The abundance of (β, 0.05; 95%CI, 0.002 ~ 0.101; = 0.041) may increase, and that of (β, -0.072; 95%CI, -0.137 ~ -0.007; = 0.030) decreased after hemorrhagic stroke according to the results of reverse MR analysis. No significant pleiotropy or heterogeneity was detected in any of the MR analyses.
CONCLUSION
There is a significant causal relationship between GM and hemorrhagic stroke. The prevention, monitoring, and treatment of hemorrhagic stroke through GM represent a promising avenue and contribute to a deeper understanding of the mechanisms underlying hemorrhagic stroke.
PubMed: 38188561
DOI: 10.3389/fmicb.2023.1290909 -
Nutrients Jul 2023Western diet (WD) intake, aging, and inactivation of farnesoid X receptor (FXR) are risk factors for metabolic and chronic inflammation-related health issues ranging...
Western diet (WD) intake, aging, and inactivation of farnesoid X receptor (FXR) are risk factors for metabolic and chronic inflammation-related health issues ranging from metabolic dysfunction-associated steatotic liver disease (MASLD) to dementia. The progression of MASLD can be escalated when those risks are combined. Inactivation of FXR, the receptor for bile acid (BA), is cancer prone in both humans and mice. The current study used multi-omics including hepatic transcripts, liver, serum, and urine metabolites, hepatic BAs, as well as gut microbiota from mouse models to classify those risks using machine learning. A linear support vector machine with -fold cross-validation was used for classification and feature selection. We have identified that increased urine sucrose alone achieved 91% accuracy in predicting WD intake. Hepatic lithocholic acid and serum pyruvate had 100% and 95% accuracy, respectively, to classify age. Urine metabolites (decreased creatinine and taurine as well as increased succinate) or increased gut bacteria (, , and ) could predict FXR deactivation with greater than 90% accuracy. Human disease relevance is partly revealed using the metabolite-disease interaction network. Transcriptomics data were also compared with the human liver disease datasets. WD-reduced hepatic (cytochrome P450 family 39 subfamily a member 1) and increased (GRAM domain containing 1B) were also changed in human liver cancer and metabolic liver disease, respectively. Together, our data contribute to the identification of noninvasive biomarkers within the gut-liver axis to predict metabolic status.
Topics: Mice; Humans; Animals; Liver; Fatty Liver; Liver Neoplasms; Inflammation; Biomarkers; Bile Acids and Salts; Mice, Inbred C57BL
PubMed: 37571345
DOI: 10.3390/nu15153406 -
Frontiers in Microbiology 2024The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the...
OBJECTIVE
The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators.
METHODS
Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization.
RESULTS
In our MR analysis, a positive correlation was observed between and the risk of juvenile idiopathic arthritis, while showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%].
CONCLUSION
Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.
PubMed: 38605717
DOI: 10.3389/fmicb.2024.1363776 -
Journal of Microbiology and... Dec 2023Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human...
Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human gut bacterium cleaving C-C glycosidic bond was screened from puerarin conversion to daidzein, and a new, gram-positive -glycoside-deglycosylating strain, sp. MRG-IFC3, was isolated from human fecal sample under anaerobic conditions. Though MRG-IFC3 biotransformed isoflavone -glycoside, it could not metabolize other -glycosides, such as vitexin, bergenin, and aloin. As evident from the production of the corresponding aglycons from various 7--glucosides, MRG-IFC3 strain also showed 7--glycoside cleavage activity; however, flavone 3--glucoside icariside II was not metabolized. In addition, for mechanism study, -glycosyl bond cleavage of puerarin by MRG-IFC3 strain was performed in DO GAM medium. The complete deuterium enrichment on C-8 position of daidzein was confirmed by H NMR spectroscopy, and the result clearly proved for the first time that daidzein is produced from puerarin. Two possible reaction intermediates, the quinoids and 8-dehydrodaidzein anion, were proposed for the production of daidzein-8d. These results will provide the basis for the mechanism study of stable -glycosidic bond cleavage at the molecular level.
Topics: Humans; Bacteria; Glycosides; Isoflavones; Glucosides; Feces
PubMed: 37789701
DOI: 10.4014/jmb.2308.08021 -
Microbiology Spectrum Jun 2023Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational... (Meta-Analysis)
Meta-Analysis
Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens , , and was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera , , , , XIV, and , were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including , were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.
Topics: Humans; Feces; RNA, Ribosomal, 16S; Bacteria; Gastrointestinal Microbiome; Lactobacillales; Osteoporosis
PubMed: 37042756
DOI: 10.1128/spectrum.00322-23 -
International Journal of Radiation... Feb 2023To explore the dynamic change of gut microbiota and its predictive role in progression-free survival (PFS) in non-small cell lung cancer (NSCLC) after concurrent... (Clinical Trial)
Clinical Trial
PURPOSE
To explore the dynamic change of gut microbiota and its predictive role in progression-free survival (PFS) in non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT).
METHODS AND MATERIALS
Forty-one patients with NSCLC in 2 phase 2 trials (NCT02573506 and NCT03006575) were analyzed. A total of 102 fecal samples were collected at 3 time points (T0, before CCRT; T1, 2 weeks after the initiation of CCRT; and T2, the end of CCRT). Gut microbiota composition and functionality were analyzed by 16S rRNA gene sequencing and shotgun metagenomics, respectively. Alpha diversity, taxonomic composition, and KEGG functional pathways were compared between patients in the long-PFS group (PFS ≥11.0 months) and short-PFS group (PFS <11.0 months). A random forest classifier was constructed to identify microbial signature related to PFS. Clinical and microbial factors potentially predictive of PFS were assessed in the univariate and multivariate Cox regression analysis.
RESULTS
The abundance of Bacteroidota and Proteobacteria increased, while the abundance of Firmicutes decreased after CCRT. Shannon index (P = .006) and PD index (P = .022) were significantly higher in the long-PFS group than for those in the short-PFS group at T1. The PFS-prediction microbial signature at T1 included unclassified members of the Lanchospiraceae spp., such as NK4A136 and UCG-003 groups, Dorea sp., various strains from within the Eubacterium hallii and E. siraeum groups, and an unclassified member of the Muribaculaceae, which yielded an area under the ROC curve of 0.87. These discriminatory genera mostly belong to phylum Firmicutes/family Clostridia. Multivariate analysis indicated PD index (HR = 8.036, P = .016) and the abundance of Dorea sp. at T1 (HR = 4.186, P = .043) were independent predictors of PFS. The KEGG pathways at T1 overrepresented in the long-PFS group included fatty acid metabolism, fatty acid biosynthesis, and arginine biosynthesis. Those overrepresented in the short-PFS group included lipopolysaccharide biosynthesis, ascorbate and aldarate metabolism, and biosynthesis of vancomycin group antibiotics.
CONCLUSIONS
Gut microbiota composition and functionality at 2 weeks after the initiation of CCRT were associated with PFS in NSCLC. Further research is needed to confirm these results.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Fatty Acids; Gastrointestinal Microbiome; Lung Neoplasms; RNA, Ribosomal, 16S
PubMed: 35905860
DOI: 10.1016/j.ijrobp.2022.07.032 -
Frontiers in Endocrinology 2023The risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut...
OBJECTIVE
The risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D.
METHODS
Google Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: "gut microbiota," "gut microbiome," "bacteria," "T1D," "type 1 diabetes," "autoimmune diabetes," "glycemic control," "glucose control," "HbA1c," "inflammation," "inflammatory," and "cytokine." The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients.
RESULTS
This review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of , , and and positively correlated with abundance of , , , and . Instead, was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients.
CONCLUSION
We draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 1; Dysbiosis; Gastrointestinal Microbiome; Glycated Hemoglobin; Glycemic Control; Inflammation
PubMed: 38034007
DOI: 10.3389/fendo.2023.1265696 -
Nutrients Nov 2023The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization...
The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization studies were conducted utilizing the data sourced from the genome-wide association study (GWAS) database for the gut microbiome, AMD, and glaucoma. Single nucleotide polymorphism (SNP) estimates were summarized through five Mendelian randomization (MR) methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables (IVs). Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Inverse variance weighted (IVW) suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggest that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggest that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Likewise, reverse MR found that glaucoma led to an increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Glaucoma; Macular Degeneration; Clostridiales; Lactobacillales
PubMed: 37960299
DOI: 10.3390/nu15214646 -
Preventive Veterinary Medicine Oct 2020
SVEPM 2019-Implications of pathogen and antimicrobial evolution on animal health, herd management and policy making, society for veterinary epidemiology and preventive medicine conference Utrecht, the Netherlands 27th-29th March 2019.
Topics: Animal Diseases; Animals; Anti-Infective Agents; Congresses as Topic; Netherlands; Policy Making; Societies; Veterinary Medicine
PubMed: 32147105
DOI: 10.1016/j.prevetmed.2019.104821 -
Frontiers in Aging Neuroscience 2023Gut-brain axis might play an important role in cognitive impairments by various diseases including Alzheimer's disease (AD).
BACKGROUND
Gut-brain axis might play an important role in cognitive impairments by various diseases including Alzheimer's disease (AD).
OBJECTIVE
To investigate the differences in gut microbial composition, intestinal barrier function, and systemic inflammation in patients with AD or mild cognitive impairment (MCI), and normal control (NC) cases.
METHODS
A total of 118 subjects (45 AD, 38 MCI, and 35 NC) were recruited. Cognitive function was assessed using Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Scale (MoCA). Functional ability was assessed using Activity of Daily Living Scale (ADL). The composition of gut microbiome was examined by 16S rRNA high-throughput sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional transfer of gut microbiota. Gut barrier dysfunction was evaluated by measuring the levels of diamine oxidase (DAO), D-lactic acid (DA), and endotoxin (ET). The serum high-sensitivity C-reactive protein (hs-CRP) level was used to indicate systemic inflammation.
RESULTS
Compared with normal controls, patients with cognitive impairments (AD and MCI) had lower abundance of and higher levels of DAO, DA, and ET. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the pathways related to glycan biosynthesis and metabolism increased in MCI patients, while the ones related to membrane transport decreased. The abundance of and was negatively correlated with the content of ET, and positively correlated with the scores of MMSE and MoCA. The hs-CRP levels were similar among the three groups. A significant negative correlation was observed between the severity of gut barrier dysfunction and cognitive function.
CONCLUSION
Cognitive impairments might be associated with gut microbial dysbiosis and intestinal barrier dysfunction.
PubMed: 37350810
DOI: 10.3389/fnagi.2023.1174599