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 (P(FDR)>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, P(FDR)=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.