Immune Inflammation as a Mediator in the Association Between Gut Microbiota–Related Diet and Depression

Corresponding author: chenling, chinglingp@163.com

DOI: 10.12201/bmr.202603.00082

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  Abstract: Objective To investigate the association between the dietary index for gut microbiota (DI-GM) and the risk of depression, and to examine the mediating role of the systemic immune-inflammation index (SII). Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2005—2018 were used, comprising 24370 participants. Depressive status was assessed using the patient health questionnaire-9 (PHQ-9). Gut microbiota-related diet quality was evaluated using DI-GM, and immune-inflammatory status was assessed using SII. Survey-weighted linear regression, logistic regression, restricted cubic spline analysis, and mediation analysis were performed to comprehensively evaluate the associations between DI-GM, SII, and depression. Results Among the participants, 6110 individuals exhibited depressive symptoms. After adjustment for multiple confounding factors, DI-GM was negatively associated with PHQ-9 scores and a reduced risk of depression. In contrast, SII was positively associated with PHQ-9 scores and an increased risk of depression. Nonlinear analysis indicated that when ln(SII)≥5.719, the risk of depression increased significantly. Mediation analysis demonstrated that SII partially mediated the association between DI-GM and depression risk, accounting for 3.56% of the total effect. Conclusion Gut microbiota-related diet quality is significantly associated with the risk of depression, and immune-inflammatory responses partially mediate this relationship. These findings suggest that improving dietary patterns and reducing systemic inflammation may help prevent depression.

  Key words: Immune System; Gastrointestinal Microbiome; Depression; Correlation study

  Submit time: 19 March 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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