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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 -
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 -
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 -
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 -
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 -
Microorganisms Jul 2023A cross-sectional study involving 224 healthy Japanese adult females explored the relationship between ramen intake, gut microbiota diversity, and blood biochemistry....
A cross-sectional study involving 224 healthy Japanese adult females explored the relationship between ramen intake, gut microbiota diversity, and blood biochemistry. Using a stepwise regression model, ramen intake was inversely associated with gut microbiome alpha diversity after adjusting for related factors, including diets, Age, BMI, and stool habits (β = -0.018; r = -0.15 for Shannon index). The intake group of ramen was inversely associated with dietary nutrients and dietary fiber compared with the no-intake group of ramen. Sugar intake, as a short-chain fatty acid (SCFA)-producing gut microbiota, and γ-glutamyl transferase as a liver function marker were directly associated with ramen intake after adjustment for related factors including diets, gut microbiota, and blood chemistry using a stepwise logistic regression model, whereas is inconsistently less abundant in the ramen group. In conclusion, the increased ramen was associated with decreased gut bacterial diversity accompanying a perturbation of through the dietary nutrients, gut microbiota, and blood chemistry, while the methodological limitations existed in a cross-sectional study. People with frequent ramen eating habits need to take measures to consume various nutrients to maintain and improve their health, and dietary management can be applied to the dietary feature in ramen consumption.
PubMed: 37630452
DOI: 10.3390/microorganisms11081892 -
Frontiers in Immunology 2023Nicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment...
BACKGROUND
Nicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment of nicotine dependence. However, the causal relationship between the two is still unclear. This study aims to investigate the causal relationship between nicotine dependence and gut microbiota.
METHODS
A two-sample bidirectional Mendelian randomization (MR) study was conducted using the largest existing gut microbiota and nicotine dependence genome-wide association studies (GWAS). Causal relationships between genetically predicted nicotine dependence and gut microbiota abundance were examined using inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO approaches. Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis were performed as sensitivity analyses to assess the robustness of the results. Multivariable Mendelian randomization analysis was also conducted to eliminate the interference of smoking-related phenotypes. Reverse Mendelian randomization analysis was then performed to determine the causal relationship between genetically predicted gut microbiota abundance and nicotine dependence.
RESULTS
Genetically predicted nicotine dependence had a causal effect on (β: -0.52, 95% CI: -0.934-0.106, P = 0.014). The group (OR: 1.106, 95% CI: 1.004-1.218), (OR: 1.118, 95% CI: 1.001-1.249) and (OR: 1.08, 95% CI: 1.001-1.167) were risk factors for nicotine dependence. (OR: 0.905, 95% CI: 0.837-0.977), (OR: 0.014, 95% CI: 0.819-0.977), (OR: 0.841, 95% CI. 0.731-0.968), (OR: 0.831, 95% CI: 0.735-0.939) and (OR: 0.838, 95% CI: 0.739-0.951) were protective factor for nicotine dependence. The sensitivity analysis showed consistent results.
CONCLUSION
The Mendelian randomization study confirmed the causal link between genetically predicted risk of nicotine dependence and genetically predicted abundance of gut microbiota. Gut microbiota may serve as a biomarker and offer insights for addressing nicotine dependence.
Topics: Humans; Tobacco Use Disorder; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Smoking; Clostridiales
PubMed: 38022531
DOI: 10.3389/fimmu.2023.1244272 -
International Journal of Molecular... Oct 2023Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing...
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in sp. and for the control samples and enrichment in (and in particular sp.) and in NAFLD. The families, , , and (particularly and ), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in and a decrease in for NAFLD patients were detected using MALDI-TOF-MS. An increase in , , , , , and , and a decrease in in NAFLD were observed with 16S NGS, and enrichment in was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
Topics: Adult; Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Fibrosis; Microbiota; Bacteroidetes; Liver
PubMed: 37894951
DOI: 10.3390/ijms242015272 -
International Journal of Molecular... Jul 2023Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid...
Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., ) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of , , , , , higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.
Topics: Humans; Gastrointestinal Microbiome; Melanoma; RNA, Ribosomal, 16S; Skin Neoplasms; Metabolome; Feces; Body Composition
PubMed: 37511376
DOI: 10.3390/ijms241411611