Causal relationships between gut microbiota, immune cell, and Henoch-Schonlein Purpura: a two-step, two-sample Mendelian randomization study
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC11349531 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Gut microbiota have been linked to immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) in recent studies, but a cause-and-effect relationship is unclear. We used Mendelian randomization (MR) to assess causal relationships between gut microbiota and HSP/ITP using summary statistics from the GWAS dataset of the international MiBioGen and FinnGen consortium. The IVW method was used as the main evaluation indicator. MR analysis of 196 intestinal flora and HSP/ITP/sTP phenotypes showed that 12 flora were potentially causally associated with ITP, 6 with HSP, and 9 with sTP. The genes predicted that genus Coprococcus3 (p = 0.0264, OR = 2.05, 95% CI 1.09-3.88)and genus Gordonibacter (p = 0.0073, OR = 1.38; 95% CI 1.09-1.75) were linked to a higher likelihood of developing ITP. Additionally, family Actinomycetaceae (p = 0.02, OR = 0.51, 95% CI 0.28-0.90) and order Actinomycetales (p = 0.0199, OR = 0.50, 95% CI 0.28-0.90) linked to reduced HSP risk. Genus Ruminococcaceae UCG013 (p = 0.0426, OR = 0.44, 95% CI 0.20-0.97) negatively correlated with sTP risk. Our MR analyses offer evidence of a possible cause-and-effect connection between certain gut microbiota species and the likelihood of HSP/ITP.
| S-EPMC11226487 | biostudies-literature
Project description:We present a rare case of a 4-year-old boy with newly diagnosed Henöch-Schonlein purpura (HSP) affecting the scrotum and penis. The patient presented to the emergency department with palpable purpura symmetrically distributed over the lower limbs. This was associated with arthritis of the right knee, abdominal pain and scrotal swelling. These symptoms were preceded by an upper respiratory tract infection (URTI). The patient was initially treated with empirical oral antibiotics for epididymitis and was discharged. He subsequently re-presented 12 days later with penile swelling, erythema and tenderness. An ultrasound scan of the penis revealed grossly oedematous subcutaneous tissue with normal penile architecture. His symptoms resolved spontaneously and the patient remains under close follow-up by the paediatric team for further sequelae of HSP.
| S-EPMC5976075 | biostudies-literature
Project description:BackgroundGut microbiota (GM) is associated with both the occurrence and development of pancreatic cancer (PC), and immune cells potentially play a role in this process. This study sought to evaluate the causative effect of GM on PC and to ascertain possible immune cell mediators.MethodsThe study primarily employed a two-step, two-sample Mendelian randomization (MR) analysis to explore the causal relationship between GM and PC within the European population, placing particular emphasis on the application of the inverse variance weighted (IVW) approach. Additionally, mediation analysis was conducted to explore the potential influence of immune cells as mediators.ResultsThe MR analysis revealed a significant association between Geminocystis and the risk of PC. Increased abundance of Geminocystis was positively associated with the risk of PC (odds ratio (OR): 2.580, 95% confidence interval (CI): 1.050 - 6.342). The validity of the outcomes was also verified by the sensitivity analysis. The mediation MR analysis showed that the B-cell absolute count served as a partial intermediary in the causal link between Geminocystis and the risk of PC, contributing to 15.321% of the mediating impact.ConclusionThis MR study demonstrated that Geminocystis has a causal relationship with PC and potentially mediates B-cell absolute count in the TBNK panel.
| S-EPMC11650607 | biostudies-literature
Project description: Not available
| S-EPMC11632987 | biostudies-literature
Project description: Not available
| S-EPMC5765245 | biostudies-literature
Project description:BackgroundDyslipidemia is often observed in rheumatic diseases, such as ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), yet it remains to be detected whether rheumatic diseases have a causal effect on dyslipidemia.MethodsSignificant (P < 5 × 10-8) and independent (r2 < 0.1) single-nucleotide polymorphisms in genome-wide association studies were selected as instrumental variables to conduct Mendelian randomization (MR) analysis. Inverse variance weighted, weighted median, and MR-Egger regression were adopted for the causal inference. Subsequently, sensitivity analysis was conducted to assess the stability and reliability of MR.ResultsThe MR results revealed positive causal relationships of AS with total cholesterol (TC) (β = 0.089, 95% CI = 0.050 to 0.128, P = 6.07 × 10-6), low-density lipoprotein (LDL) (β = 0.087, 95% CI = 0.047 to 0.127, P = 1.91 × 10-5), and high-density lipoprotein (HDL) (β = 0.043, 95% CI = 0.001 to 0.074, P = 0.009). There was no causal effect of RA on TC (β = 0.008, 95% CI = 4.86 × 10-4 to 0.017, P = 0.064), LDL (β = 6.4 × 10-4, 95% CI = -0.008 to 0.007, P = 0.871), or HDL (β = 0.005, 95% CI = -0.003 to 0.013, P = 0.200). Additionally, SLE had negative causal links for TC (β = -0.025, 95% CI = -0.036 to -0.015, P = 4.42 × 10-6), LDL (β = -0.015, 95% CI = -0.025 to -0.005, P = 0.003), and HDL (β = -0.013, 95% CI = -0.021 to -0.004, P = 0.004). The results were stable and reliable.ConclusionThis study suggested positive causal effects of AS on TC, LDL, and HDL and negative causal effects of SLE on these cholesterol levels, which could provide much help for the pathogenesis and treatment of rheumatic disease patients with dyslipidemia.
| S-EPMC9470850 | biostudies-literature
Project description:BackgroundNumerous clinical studies have investigated the association between schizophrenia and psoriasis, but the findings remain inconsistent.MethodsWe employed Mendelian randomization (MR) methods to evaluate the causal relationship between schizophrenia and psoriasis and its subtypes. Inverse variance weighting was used as the primary approach for MR analysis, complemented by inverse magnetic resonance analysis and sensitivity testing. To identify potential mediators, we applied a two-step MR approach. Additionally, pathway and functional enrichment analyses were conducted to uncover possible mechanisms linking schizophrenia and psoriasis.ResultsMR analysis indicated an association between schizophrenia and psoriasis (OR: 1.0010; p = 0.008). Subtype analyses revealed that genetic susceptibility increased the risk of developing psoriasis vulgaris (OR: 1.18; 95% CI: 1.03-1.34; p = 0.016) but was not significantly associated with arthropathy (OR: 1.04; 95% CI: 0.97-1.12; p = 0.292). Emotional states such as tenseness, tiredness, and misery fulfil the criteria of the MR two-step approach and can be considered as potential mediators of the association between schizophrenia and psoriasis vulgaris. Pathway and functional enrichment analyses suggested the involvement of oxidative stress-driven hypothalamic-pituitary-adrenal (HPA) axis pathways in the link between schizophrenia and psoriasis.ConclusionOur MR study established a significant association between schizophrenia and psoriasis vulgaris, identifying tenseness, tiredness, and misery as potential mediators. Pathway and functional enrichment analyses indicated that oxidative stress in the HPA axis may represent a shared mechanism underlying schizophrenia and psoriasis.
| S-EPMC11924594 | biostudies-literature
Project description:Background: Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung cancer (NSCLC) and whether it can be mediated by immune cells is still unknown. Methods: We performed a two-step, two-sample Mendelian randomization study with an Inverse variance weighted (IVW) approach to investigate the causal role of GM on NSCLC and the mediation effect of immune cells between the association of GM and NSCLC. Results: MR analyses determined the protective effects of 6 genera on NSCLC (Bacteroides, Roseburia, Alistipes, Methanobrevibacter, Ruminococcus gauvreauii group, and Peptococcus). In addition, 38 immune cell traits were suggestively associated with NSCLC. Of note, the mediation MR illustrated the causal role of Genus-Peptococcus on NSCLC (Total effect IVW: OR = 0.790, 95% CI [0.657, 0.950], P = 0.012) was to a large proportion mediated by CD45 on HLA DR+ CD4+ in TBNK panel (-034 (95% CI [-0.070, -0.005]; P = 0.037), accounting for 14.4% of Total effect). Conclusion: The study suggested a causal relationship between GM and NSCLC, which may be mediated by immune cells.
| S-EPMC10905411 | biostudies-literature
Project description:Previous observational studies have investigated the relationship between obesity and the biliary tract and pancreas. The causality, however, is still to be confirmed. This study was designed to explore the causality between obesity which included body mass index(BMI), circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR), and pancreatobiliary diseases with a Two-Sample Mendelian Randomization(MR) analysis. single-nucleotide polymorphisms used in our study were derived from genome-wide association studies (GWAS). The inverse variance weighted was the dominated method to evaluate the causality. The heterogeneity was validated by Cochran's Q test. The pleiotropy was validated by MR-Egger regression and MR-PRESSO. The stability and reliability of the results were illustrated by the 'leave-one-out'sensitivity analysis. The MR results explored positive causal effects of BMI (OR: 1.021; 95% CI: from 1.016 to 1.027; P = 4.25 × 10-15) and WC (OR: 1.021; 95% CI: from 1.015 to 1.028; P = 1.65 × 10-10) on pancreatobiliary diseases. However, no causality existed between HC, WHR and pancreatobiliary diseases. This study reminded that general obesity and abdominal obesity required weight loss to prevent pancreatic biliary disease.
| S-EPMC10393843 | biostudies-literature
Project description:ObjectiveHenoch-Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch-Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch-Schönlein purpura.MethodThe medical records of children newly diagnosed as having Henoch-Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively.ResultsThis study included a total of 186 patients with Henoch-Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement.ConclusionsFemale sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch-Schönlein purpura.
| S-EPMC9432244 | biostudies-literature