Mendelian randomization supports causality between gut microbiota and chronic hepatitis B

Zhang, Quanzheng; Zhou, Jinhua; Zhang, Xiaoxiao; Mao, Rui; Zhang, Chuan

doi:10.3389/fmicb.2023.1243811

Cited by 10 publications

(3 citation statements)

References 53 publications

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“…The Genus Eubacterium ventriosum group is a component of the Family Lachnospiraceae . The Genus Ruminococcus gauvreauii group belongs to the Family Ruminococcaceae and is a component of the Phylum Firmicutes ( Zhang et al, 2023 ). The association between these two genera and DN has not been examined by conventional epidemiological studies.…”

Section: Discussionmentioning

confidence: 99%

Association between gut microbiota and diabetic nephropathy: a mendelian randomization study

Jin,

Han,

Yang

et al. 2024

Front. Microbiol.

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BackgroundThe correlation between diabetic nephropathy (DN) and gut microbiota (GM) has been suggested in numerous animal experiments and cross-sectional studies. However, a causal association between GM and DN has not been ascertained.MethodsThis research adopted MR analysis to evaluate the causal link between GM and DN derived from data acquired through publicly available genome-wide association studies (GWAS). The study utilized the inverse variance weighted (IVW) approach to assess causal association between GM and DN. Four additional methods including MR-Egger, weighted median, weighted mode, and simple mode were employed to ensure comprehensive analysis and robust results. The Cochran’s Q test and the MR-Egger method were conducted to identify heterogeneity and horizontal pleiotropy, respectively. The leave-one-out approach was utilized to evaluate the stability of MR results. Finally, a reverse MR was performed to identify the reverse causal association between GM and DN.ResultsAccording to IVW analysis, Class Verrucomicrobiae (p = 0.003), Order Verrucomicrobiales (p = 0.003), Family Verrucomicrobiaceae (p = 0.003), Genus Akkermansia (p = 0.003), Genus Catenibacterium (p = 0.031), Genus Coprococcus 1 (p = 0.022), Genus Eubacterium hallii group (p = 0.018), and Genus Marvinbryantia (p = 0.023) were associated with a higher risk of DN. On the contrary, Class Actinobacteria (p = 0.037), Group Eubacterium ventriosum group (p = 0.030), Group Ruminococcus gauvreauii group (p = 0.048), Order Lactobacillales (p = 0.045), Phylum Proteobacteria (p = 0.017) were associated with a lower risk of DN. The sensitivity analysis did not identify any substantial pleiotropy or heterogeneity in the outcomes. We found causal effects of DN on 11 GM species in the reverse MR analysis. Notably, Phylum Proteobacteria and DN are mutually causalities.ConclusionThis study identified the causal association between GM and DN with MR analysis, which may enhance the understanding of the intestinal-renal axis and provide novel potential targets for early non-invasive diagnosis and treatment of DN.

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Section: Discussionmentioning

confidence: 99%

Association between gut microbiota and diabetic nephropathy: a mendelian randomization study

Jin,

Han,

Yang

et al. 2024

Front. Microbiol.

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“…Holdemania sp900120005 belongs to Holdemania. Holdemania is a pathogenic bacterium that has been found in various environments and poses a potential threat to human health [41]. Studies have shown an elevated presence of Holdemania in in ammatory and psychiatric disorders, indicating its pathogenic nature [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

He,

Luo,

et al. 2024

Preprint

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Background: Numerous studies have indicated a correlation between the gut microbiota (GM) and acute pancreatitis (AP), yet the precise causal relationship between them remains ambiguous. Methods: A two-sample Mendelian randomization (MR) study was conducted utilizing aggregated data from genome-wide association studies (GWASs) of 471 taxa (11 phyla, 19 orders, 24 orders, 62 families, 146 genera, and 209 species) and AP patients. Various methods, including inverse variance weighting (IVW), MR‒Egger, weighted medians, simple mode, and weighted mode, were employed to assess the causal association between the GM and AP. Sensitivity analyses were conducted utilizing Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO, followed by reverse MR analysis to evaluate the potential reverse causality between AP and GM. Results: Three gut microbial taxa were found to have significant associations with acute pancreatitis (AP). The inverse variance weighted (IVW) results revealed that Coprobacillus (OR 1.19, 95% CI 1.01 to 1.40, p=0.035) and Holdemania sp900120005 (OR 1.18, 95% CI 1.02 to 1.35, p=0.023) were identified as risk factors for the development of AP, while Megamonas (OR: 0.87, 95% CI: 0.77 to 0.98, p=0.023) was found to be a protective factor against the occurrence of AP. A thorough sensitivity analysis confirmed the reliability of our findings. Reverse Mendelian randomization (MR) analysis did not indicate any causal relationship between AP and the gut microbiota (GM). Conclusions: This study revealed a complex causal relationship between 3 GM taxa and AP, providing new evidence for the development of AP from a genetic perspective.

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“…Additionally, an increase in both the Bilophila and Ruminococcaceae genera affects the reproductive performance of sows [45]. Chronic hepatitis B patients showed a correlation between an increase in the genus Holdemania and a heightened risk of chronic hepatitis B [46]. Elevated blood urea nitrogen levels in children with idiopathic nephrotic syndrome positively correlate with the Ruminococcaceae genus [47].…”

Section: Discussionmentioning

confidence: 99%

The Dose–Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats

Mo,

Wang,

Meng

et al. 2023

Metabolites

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Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed “gut microbiome perturbations”, have emerged as plausible intermediaries in the onset or exacerbation of diseases following environmental chemical exposures, with fluoride being a compound of particular concern. Despite the well-documented adverse impacts of excessive fluoride on various human physiological systems—ranging from skeletal to neurological—the nuanced dynamics between fluoride exposure, the gut microbiome, and the resulting dose–response relationship remains a scientific enigma. Leveraging the precision of 16S rRNA high-throughput sequencing, this study meticulously examines the ramifications of diverse fluoride concentrations on the gut microbiome’s composition and functional capabilities within Wistar rats. Our findings indicate a profound shift in the intestinal microbial composition following fluoride exposure, marked by a dose-dependent modulation in the abundance of key genera, including Pelagibacterium, Bilophila, Turicibacter, and Roseburia. Moreover, discernible alterations were observed in critical functional and metabolic pathways of the microbiome, such as D-lyxose ketol-isomerase and DNA polymerase III subunit gamma/tau, underscoring the broad-reaching implications of fluoride exposure. Intriguingly, correlation analyses elucidated strong associations between specific bacterial co-abundance groups (CAGs) and these shifted metabolic pathways. In essence, fluoride exposure not only perturbs the compositional equilibrium of the gut microbiota but also instigates profound shifts in its metabolic landscape. These intricate alterations may provide a mechanistic foundation for understanding fluoride’s potential toxicological effects mediated via gut microbiome modulation.

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Mendelian randomization supports causality between gut microbiota and chronic hepatitis B

Cited by 10 publications

References 53 publications

Association between gut microbiota and diabetic nephropathy: a mendelian randomization study

Association between gut microbiota and diabetic nephropathy: a mendelian randomization study

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

The Dose–Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats

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