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. 2024 Oct 28;23(1):133.
doi: 10.1186/s12937-024-01038-9.

Breakfast skipping is linked to a higher risk of major depressive disorder and the role of gut microbes: a mendelian randomization study

Xingzhi Guo  1   2 , Wei Li  3 , Chen Hou  4 , Rui Li  5   6
Affiliations

Breakfast skipping is linked to a higher risk of major depressive disorder and the role of gut microbes: a mendelian randomization study

Xingzhi Guo et al. Nutr J. .

Abstract

Background: Observational studies have indicated that breakfast skipping and gut microbiome dysbiosis are associated with a higher risk of major depressive disorder (MDD). However, it remains unknown whether the alteration of gut microbes is implicated in the associations between breakfast skipping and MDD.

Methods: Leveraging genome-wide association studies (GWAS) on breakfast skipping, gut microbes, and MDD, we conducted a two-step Mendelian randomization (MR) study to determine the causal associations between breakfast skipping (N = 193,860) and MDD (N = 1,815,091), and evaluate the role of gut microbes (N = 18,340). Genetic variants with a P-value less than 5E-08 were selected as instrumental variables (IVs). The false discovery rate (FDR) method was employed to correct the P-values for multiple tests in gut microbes.

Results: Breakfast skipping was associated with an increased risk of MDD (odds ratio [OR] = 1.36, 95%CI = 1.12-1.65, P = 0.002), but no effect of MDD on breakfast skipping was observed (β per doubling odds of MDD =-0.001, 95%CI=-0.024 to 0.023, P = 0.957). After adjusting for multiple comparisons, the MR analysis provided little evidence for an association between breakfast skipping and the abundance of any gut microbes (PFDR>0.05). Among the 21 gut microbes with IVs available, only the abundance of Class Actinobacteria was causally associated with a reduced risk of MDD (OR = 0.85, 95%CI = 0.75-0.97, PFDR=0.015).

Conclusions: Our findings demonstrated that breakfast skipping was associated with an increased risk of MDD, but provided little evidence supporting the role of the abundance of gut microbes in it. Further efforts with a large sample size are warranted to clarify the findings.

Keywords: Breakfast skipping; Major depressive disorder; Mendelian randomization; Microbiome.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The flowchart for this Mendelian randomization analysis. Two-sample Mendelian randomization (MR) analysis assesses the effect of breakfast skipping on MDD (A). Two-step Mendelian randomization (TSMR) evaluates the effect of breakfast skipping on gut microbes (Step 1) and the effect of gut microbes on major depressive disorder (MDD) (Step 2) (B). Red signs mean that genetic variants are not associated with confounders and outcomes. LD, linkage disequilibrium
Fig. 2
Fig. 2
Bi-directional Mendelian randomization analysis between breakfast skipping and major depressive disorder. Using a P-value threshold of 5E-08, genetic predisposition to higher breakfast skipping frequency was associated with an increased major depressive disorder (MDD) (A). OR represented the risk change of MDD per unit increase in breakfast skipping. However, MDD was not linked with the susceptibility to breakfast skipping (B). Beta (β) coefficients represented the change in breakfast skipping per doubling odds of MDD. SNP, single nucleotide polymorphism; N, number
Fig. 3
Fig. 3
Scatter plots and leave-one-out plots for Mendelian randomization analysis between breakfast skipping and major depressive disorder. Bi-directional Mendelian randomization (MR) analysis using IVW, weighted median, weighted mode, and MR–Egger to evaluate the causal relationship between breakfast skipping and MDD. A showed the SNPs’ effect on breakfast skipping and major depressive disorder (MDD). B showed the SNPs’ effect on MDD and breakfast skipping. Leave-one-out analysis plots for breakfast skipping on MDD (C) and MDD on breakfast skipping (D). SNP, single nucleotide polymorphism; IVW, inverse-variance weighted; MR, Mendelian randomization
Fig. 4
Fig. 4
Causal effects of breakfast skipping on gut microbe and gut microbes on major depressive disorder. A showed the causal effect of breakfast skipping on the abundance of five gut microbes with a P value less than 0.1. Beta (β) coefficients represented the change in gut microbes per unit increase in breakfast skipping. B showed the causal effect of the abundance of 3 gut microbes on the risk of major depressive disorder (MDD) with a P value less than 0.1. OR represented the risk change of MDD per standard deviation (SD) increase in corresponding gut microbes. SNP, single nucleotide polymorphism; OR, odds ratio; FDR, false discovery rate; N, number
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