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. 2023 Oct 20;15(20):4445.
doi: 10.3390/nu15204445.

Causal Associations between Gut Microbiota and Different Types of Dyslipidemia: A Two-Sample Mendelian Randomization Study

Xuyi Zhou  1 , Peiqi Lian  1 , Hui Liu  1 , Yinghui Wang  1 , Meijuan Zhou  1 , Zhijun Feng  1
Affiliations

Causal Associations between Gut Microbiota and Different Types of Dyslipidemia: A Two-Sample Mendelian Randomization Study

Xuyi Zhou et al. Nutrients. .

Abstract

The determination of a causal association between gut microbiota and a range of dyslipidemia remains uncertain. To clarify these associations, we employed a two-sample Mendelian randomization (MR) analysis utilizing the inverse-variance weighted (IVW) method. This comprehensive analysis investigated the genetic variants that exhibited a significant association (p < 5 × 10-8) with 129 distinct gut microbiota genera and their potential link to different types of dyslipidemia. The results indicated a potential causal association between 22 gut microbiota genera and dyslipidemia in humans. Furthermore, these findings suggested that the impact of gut microbiota on dyslipidemia regulation is dependent on the specific phylum, family, and genus. Bacillota phylum demonstrated the greatest diversity, with 15 distinct genera distributed among eight families. Notably, gut microbiota-derived from the Lachnospiraceae and Lactobacillaceae families exhibit statistically significant associations with lipid levels that contribute to overall health (p < 0.05). The sensitivity analysis indicated that our findings possess robustness (p > 0.05). The findings of our investigation provide compelling evidence that substantiates a causal association between the gut microbiota and dyslipidemia in the human body. It is noteworthy to highlight the significant influence of the Bacillota phylum as a crucial regulator of lipid levels, and the families Lachnospiraceae and Lactobacillaceae should be recognized as probiotics that significantly contribute to this metabolic process.

Keywords: causal associations; dyslipidemia; gut microbiota; mendelian randomization study.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The forest map illustrates the results of Mendelian randomization (MR) analysis, indicating the impact of various gut microbiota genera on different lipid levels. A-F, the MR analysis demonstrates diverse effects of gut microbiota genera on HDL-C (A), LDL-C (B), TC (C), TG (D), APOA1 (E), and APOB (F). nSNP, number of single nucleotide polymorphism; SE, standard error; OR, odds ratio; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; triglyceride, TG; total cholesterol, TC; apolipoprotein A1, APOA1; apolipoprotein B, APOB.
Figure 2
Figure 2
Scatter plot demonstrates a significant linear association between distinct gut microbiota genera and various forms of lipid metabolism within the human body, while no discernible heterogeneity of single nucleotide polymorphisms (SNPs) was observed. The black dots correspond to the single nucleotide polymorphisms (SNPs) employed in the Mendelian randomization analysis. The lines depict the linear fitting trends derived from various analysis methods employed in the Mendelian randomization analysis. The red line represents the fitting trend obtained through the inverse variance weighted (IVW) method, the dark blue line represents the fitting trend obtained through the MR-Egger method, the green line represents the fitting trend obtained through the weighted median method, the light red line represents the fitting trend obtained through the weighted mode method, and the light yellow green line represents the fitting trend obtained through the simple mode method. high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; triglyceride, TG; total cholesterol, TC; apolipoprotein A1, APOA1; apolipoprotein B, APOB; SNP, single nucleotide polymorphisms.
Figure 3
Figure 3
A comprehensive overview of the distribution of gut microbiota genera at the phylum and family levels, highlighting the subsequent influence on lipid levels. The red triangle represents the increasing effect, while the blue triangle represents the reducing effect. high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; triglyceride, TG; total cholesterol, TC; apolipoprotein A1, APOA1; apolipoprotein B, APOB.
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