The predictive, preventive, and personalized medicine of depression: gut microbiota and inflammation.

BACKGROUND

Gut microbiota (GM) is closely associated with the onset of depression, in which inflammation plays an essential role. Identifying specific GM associated with depression and their mechanisms, based on the principles of predictive, preventive, and personalized medicine (PPPM), is a critical step toward achieving targeted prevention and personalized treatment for depression.

WORKING HYPOTHESIS AND METHODOLOGY

We hypothesized that both gut microbiota (GM) and cytokines influence the onset of depression, with cytokines acting as mediators of GM effects on depression. To test this hypothesis, we employed univariate Mendelian Randomization (UVMR) analysis to identify GM taxa associated with depression and cytokines and to determine the potential role of the identified GM taxa on these cytokines. Subsequently, multivariate Mendelian randomization (MVMR) was used to infer the mediating role of cytokines between the identified differential genus of GM and depression. Our results indicate that immune imbalance due to intestinal dysbiosis serves as an early risk indicator for the onset of depression. This provides a basis for utilizing non-invasive stool detection of GM for early screening, timely prevention, and personalized treatment of depression. By combining non-invasive stool detection of GM with existing methods, such as psychological questionnaires, we can jointly predict and assess the risk of developing depression. Additionally, formulating personalized treatment protocols that combine probiotics and medication can help transition depression management from reactive medicine to predictive, preventive, and personalized medicine (PPPM).

RESULTS

UVMR identified 15 GM taxa and 4 cytokines associated with the onset of depression. Specifically, , , , and circulating ADA, IL-18R1 were all inferred to be protective factors against the onset of depression. Conversely, , , , VEGF_A, and TNFSF14 were inferred as risk factors for the onset of depression. Further, MVMR validated the mediating role of some cytokines in the effects of GM on depression.

CONCLUSIONS

Our study highlights the influence of alterations in GM on depression, revealing a mediating role of inflammation. By regulating these specific GM, it is hoped that the clinical treatment of depression can be transformed from traditional medicine to PPPM. With the help of mendelian randomization (MR) method, this study provides support for the wide application of non-invasive stool detection of GM for early screening of depression in clinical and carries out precise treatment based on the screening results, targeting the supplementation of specific bacteria, correcting the immune imbalance to prevent depression, and mitigating or blocking the disease process of depression.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s13167-024-00379-z.