Associations between Serum Mineral Nutrients, Gut Microbiota, and Risk of Neurological, Psychiatric, and Metabolic Diseases: A Comprehensive Mendelian Randomization Study

Abstract

Recent observational studies have reported associations between serum mineral nutrient levels, gut microbiota composition, and neurological, psychiatric, and metabolic diseases. However, the causal effects of mineral nutrients on gut microbiota and their causal associations with diseases remain unclear and require further investigation. This study aimed to identify the associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases using Mendelian randomization (MR). We conducted an MR study using the large-scale genome-wide association study (GWAS) summary statistics of 5 serum mineral nutrients, 196 gut microbes at the phylum, order, family, and genus levels, and a variety of common neurological, psychiatric, and metabolic diseases. Initially, the independent causal associations of mineral nutrients and gut microbiota with diseases were examined by MR. Subsequently, the causal effect of mineral nutrients on gut microbiota was estimated to investigate whether specific gut microbes mediated the association between mineral nutrients and diseases. Finally, we performed sensitivity analyses to assess the robustness of the study results. After correcting for multiple testing, we identified a total of 33 causal relationships among mineral nutrients, gut microbiota, and diseases. Specifically, we found 4 causal relationships between 3 mineral nutrition traits and 3 disease traits, 15 causal associations between 14 gut microbiota traits and 6 disease traits, and 14 causal associations involving 4 mineral nutrition traits and 15 gut microbiota traits. Meanwhile, 118 suggestive associations were identified. The current study reveals multiple causal associations between serum mineral nutrients, gut microbiota, risk of neurological, psychiatric, and metabolic diseases, and potentially provides valuable insights for subsequent nutritional therapies.

Keywords: gut microbiota; mendelian randomization study; metabolic diseases; mineral nutrient; neurological diseases; psychiatric diseases.

Figure 1

Descriptions of the overall workflow of MR analysis.

Figure 2

Balloon plot of the association between exposure and outcome. (A) Balloon plot of the association between gut microbiota and diseases (p-value < 0.05 and q-value < 0.10). (B) Balloon plot of the association between mineral nutrition and gut microbiota. Red represents a positive correlation; blue represents a negative correlation, with OR = 1 as the threshold.

Figure 3

Mendelian randomization results of causal effects between mineral nutrients, gut microbiota, and diseases (p-value < 0.05 and q-value < 0.10). OR, odds ratio; CI, confidence interval; IVW, inverse variance weighted.

Figure 4

Mendelian randomization results of causal effects between mineral nutrients and gut microbiota (p-value < 0.05 and q-value < 0.10). OR, odds ratio; CI, confidence interval; IVW, inverse variance weighted.

Figure 5

The causal associations between mineral nutrients, gut microbiota, and diseases by Mendelian randomization analysis (p-value < 0.05, q-value < 0.10). The thickness of the lines is positively correlated with the absolute value of the “OR-1”. The lines start with the exposure and end with the outcome. Red lines represent a positive correlation; blue lines represent a negative correlation. Green nodes represent mineral nutrient traits, purple nodes represent gut microbiota traits, orange nodes represent disease traits, and the size of the node represents the sum of the in-degree and out-degree.