Different roles of microbiota and genetics in the prediction of treatment response in major depressive disorder

The roles of gut microbiota and susceptibility genes in patients with major depression disorder (MDD) are not well understood. Examining the microbiome and host genetics might be helpful for clinical decision-making. Patients with MDD were recruited in this study and subsequently treated for eight weeks. We identified the differences between the population with a response after two weeks and those with a response after eight weeks. The factors that were significantly correlated with efficacy were used to predict the treatment response. The differences in the importance of microbiota and genetics in prediction were analyzed. Our study identified rs58010457 as a potentially key locus affecting the treatment effect. Different microbiota and enriched pathways might play different roles in the response after two and eight weeks. We found that the area under the curve (AUC) value was greater than 0.8 for both random forest models. The contribution of different components to the AUC was evaluated by removing genetic information, microbiota abundance, and pathway data. The gut microbiome was an important predictor of the response after eight weeks, while genetics was an important predictor of the response after two weeks. These results suggested a dynamic effect of interaction among genetics and gut microbes on treatment. Furthermore, these results provide new guidance for clinical decisions: in cases of inadequate treatment effects after two weeks, the composition of the intestinal flora can be improved by diet therapy, which could ultimately affect the efficacy.