Dataset Information

Mendelian randomization reveals association of gut microbiota with Henoch-Schonlein purpura and immune thrombocytopenia.

ABSTRACT: 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.

SUBMITTER: Jiang C

PROVIDER: S-EPMC11226487 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Mendelian randomization reveals association of gut microbiota with Henoch-Schönlein purpura and immune thrombocytopenia.

Jiang Chendong C Deng Shu S Ma Xiaohan X Song Juan J Li Jinpeng J Yuan Enwu E

International journal of hematology 20240426 1

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 t ...[more]

PMID: 38671184

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Project description:Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch-Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

Project description:Immunoglobulin A vasculitis (IgAV; formerly Henoch Schonlein Purpura) is the most common form of childhood vasculitis. It can occur in any age and peaks around 4-6 years old. It demonstrates seasonal variation implicating a role for environmental triggers and geographical variation. The diagnosis is made clinically and 95% of patients will present with a rash, together with any from a triad of other systems-gastrointestinal, musculoskeletal, and renal. Most cases of IgAV in children have an excellent outcome. Treatment may be required during the acute phase for gastrointestinal involvement and renal involvement, termed IgAV nephritis (previously HSP nephritis), is the most serious long-term manifestation accounting for ~1-2% of all childhood end stage kidney disease (ESKD). It therefore requires a period of renal monitoring conducted for 6-12 months. Patients presenting with nephrotic and/or nephritic syndrome or whom develop significant persistent proteinuria should undergo a renal biopsy to evaluate the extent of renal inflammation and there are now international consensus guidelines that outline the indications for when to do this. At present there is no evidence to support the use of medications at the outset in all patients to prevent subsequent renal inflammation. Consensus management guidelines suggest using oral corticosteroids for milder disease, oral, or intravenous corticosteroids plus azathioprine or mycophenolate mofetil or intravenous cyclophosphamide for moderate disease and intravenous corticosteroids with cyclophosphamide for severe disease. Angiotensin system inhibitors act as adjunctive treatment for persisting proteinuria and frequently relapsing disease may necessitate the use of immunosuppressant agents. Renal outcomes in this disease have remained static over time and progress may be hindered due to many reasons, including the lack of reliable disease biomarkers and an absence of core outcome measures allowing for accurate comparison between studies. This review article summarizes the current evidence supporting the management of this condition highlighting recent findings and areas of unmet need. In order to improve the long term outcomes in this condition international research collaboration is urgently required.

Dataset Information

Mendelian randomization reveals association of gut microbiota with Henoch-Schonlein purpura and immune thrombocytopenia.

Publications

Mendelian randomization reveals association of gut microbiota with Henoch-Schönlein purpura and immune thrombocytopenia.

Similar Datasets

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