Exploring the causal effects of the gut microbiome on serum lipid levels: A two-sample Mendelian randomization analysis

Guo, Gongjie; Wu, Yihe; Liu, Yingjian; Wang, Zixian; Xu, Guifeng; Wang, Xipei; Liang, Feiqing; Lai, Wen‐Ter; Xiao, Xiao; Zhu, Qian; Zhong, Shilong

doi:10.3389/fmicb.2023.1113334

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…The outcomes of reverse MR are shown in Table 3 . There was no significant causality association using the IVW method, suggesting there is no evidence of a causal effect on the risk of AAA by identified gut microbiomes ( Guo et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

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Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Qiu,

Hou,

Wei

et al. 2024

Front. Microbiol.

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BackgroundPrevious studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear.MethodsA two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10−5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality.ResultsThe phylum Firmicutes (OR = 0.62; 95% CI, 0.48–0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62–0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62–0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05).ConclusionOur MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

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Section: Resultsmentioning

confidence: 99%

“…In this MR study, we used the locus-wide significance threshold ( p < 1 × 10 −5 ) to obtain more relevant IVs ( Jia et al, 2019 ; Lv et al, 2021 ; Guo et al, 2023 ; Li et al, 2023 ). Moreover, to ensure the independence of IVs, a clumping procedure with a stringent threshold ( r 2 < 0.001, kb = 10,000) was conducted.…”

Section: Methodsmentioning

confidence: 99%

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Qiu,

Hou,

Wei

et al. 2024

Front. Microbiol.

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“…The 2-sample MR analyses were carried out for the bacterial taxa or plasm protein with at least 3 IVs. The inverse variance weighted (IVW) method was acknowledged as the dominant statistical analysis method, [ 22 ] which was supplemented with robust multiple MR methods, including weighted median, Weighted mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) approaches. The causal associations are considered statistically significant if the P value of the IVW method is <.05.…”

Section: Methodsmentioning

confidence: 99%

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis

Yang,

Xu,

Liang

et al. 2024

Medicine

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It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

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“…259 Mendelian randomization analysis has also been used to support a potential causal pathway between specific gut microbiota and dyslipidemia. 260 In contrast, a reverse relationship is not supported, and elevated plasma lipid levels may not significantly affect gut microbiota; however, bile acids may mediate relationships between microbiota and lipids. 261…”

Section: Effects Of Gut Microbiota On Lipid Metabolismmentioning

confidence: 99%

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Gabriel

Ferguson

2023

Circulation Research

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Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.

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Exploring the causal effects of the gut microbiome on serum lipid levels: A two-sample Mendelian randomization analysis

Cited by 16 publications

References 44 publications

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

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