Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study

Cao, Feng; Pan, Feng; Gong, Xin; Wang, Wen; Xu, Yanyan; Cao, Pengwei; Wang, Yong

doi:10.3389/fmicb.2023.1285982

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…There are also supporting studies despite which Defluviitaleaceae studies are limited. Cao et al ( 2023 ) proved that Defluviitaleaceae were protective factors for visceral adipose tissue production, while Warbeck et al ( 2021 ) reported that the abundance of Defluviitaleaceae was higher in the treatment group of celiac disease than controls. Although no significant results were found in the enrichment analyses of related genes of IVs, interacting transcription factors in Supplementary Table S12 were investigated as a suggestive reference, in the results of which the FoxO and JAK-STAT pathways are ranked at the top.…”

Section: Discussionmentioning

confidence: 99%

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism”

Zhang,

Li,

Wang

et al. 2024

Front. Microbiol.

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IntroductionHypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways.Materials and methodsIn Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed.ResultsIn Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005–0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172–0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046–0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029–0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004–0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002–0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676–0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644–0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123–3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953–2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms.ConclusionDefluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism” and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

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Section: Discussionmentioning

confidence: 99%

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism”

Zhang,

Li,

Wang

et al. 2024

Front. Microbiol.

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Growth hormone attenuates obesity and reshapes gut microbiota in high-fat diet-fed mice

Wang,

Ran,

Zhang

et al. 2024

Metabolism Open

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Genome-wide association analysis of gut microbiome and serum metabolomics identifies heart failure therapeutic targets

Li,

Ma,

Zhang

et al. 2024

Preprint

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Background Previous investigations have established a correlation between the gut microbiota and heart failure (HF). Nevertheless, the causal relationship and potential mediators between these two factors remain elusive. In this study, we aim to elucidate the causal relationship and identify potential serum metabolites that regulate the gut microbiota and HF from a genetic perspective. Our ultimate goal is to uncover potential targets for the prevention and treatment of heart failure. Methods Two-sample bidirectional Mendelian randomization (MR) and mediated Mendelian randomization studies were conducted using pooled statistics from genome-wide association studies of 211 gut microbial taxa (MiBioGen, n = 18340), 486 serum metabolites (n = 7824), and heart failure (47,309 cases and 93,0014 controls). Inverse variance weighted estimation (IVW) was used as the primary analysis method, with Weighted median (WM), MR-Egger, Simple mode, and Weighted mode as complementary analyses. Pleiotropy and heterogeneity were assessed using MR-PRESSO, MR-Egger intercept, and Cochran's Q statistical analysis. A multivariate MR method based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal serum metabolites, and metabolic pathway analyses were performed using MetbraAnalyst 5.0 software. Results Among the 211 gut microbiota categories, 10 were causally associated with heart failure risk, including Genus Eubacterium eligens group (OR = 1.126, 95% CI = 1.017–1.247, P = 0.023). Of the 486 human circulating metabolites, 13 with known structure such as Isoleucine (OR = 1.978, 95% CI = 1.191–3.287, P = 0.008) were causally associated with heart failure risk. The top three serum metabolites with the strongest causal association with heart failure were pyroglutamine (marginal inclusion probability(MIP) = 0.609, model averaged causal effect(MACE) = 0.141), isoleucin (MIP = 0.591, MACE = 0.354), and cholesterol (MIP = 0.59, MACE = 0.266). Mediator MR analysis indicated that Isoleucine may mediate 23.86% of the causal effect of Genus Eubacterium eligens group on heart failure. Further metabolic pathway analysis revealed that the "Valine, leucine and isoleucine biosynthesis" pathway may be involved in the development of heart failure. Conclusions Our findings suggest that specific gut microbial taxa and serum metabolites are independently associated with heart failure risk. Notably, Isoleucine emerged as a significant determinant of heart failure, potentially mediating the relationship between gut microbiota and heart failure. Furthermore, our results indicate that the "Valine, leucine and isoleucine biosynthesis" pathway may play a role in the development of heart failure. In summary, our research provides novel insights into the potential targets for prevention and treatment of heart failure, focusing on the interplay between intestinal flora and circulating metabolites in the human body.

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Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study

Cited by 3 publications

References 53 publications

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism”

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism”

Growth hormone attenuates obesity and reshapes gut microbiota in high-fat diet-fed mice

Genome-wide association analysis of gut microbiome and serum metabolomics identifies heart failure therapeutic targets

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