# The Gut Microbiota as a Mediator in the Relationship Between Dietary Patterns and Depression

## TL;DR

This study shows that healthy diets, like the Mediterranean diet, are linked to gut microbes that may help reduce depression in older adults.

## Contribution

The study is among the first to show that gut microbiota mediate the relationship between diet and depression.

## Key findings

- Healthy diets like Mediterranean and DASH are linked to gut microbes associated with lower depressive symptoms.
- Gut microbiota partially mediate the relationship between Mediterranean diet adherence and depression scores.
- Unhealthy diets are associated with fewer protective gut microbial genera.

## Abstract

The interplay between diet, gut microbiota, and depressive symptoms is increasingly recognized, but underlying mechanisms remain unclear. We investigated whether adherence to several dietary patterns relates to gut microbial signatures and whether these profiles are associated with depressive symptoms in an elderly Mediterranean cohort. In 644 participants, 16S ribosomal RNA gene sequencing and dietary intake from a food‐frequency questionnaire were obtained at baseline and 1‐year follow‐up. Adherence scores were computed for the Mediterranean diet adherence score (MEDAS), energy‐reduced MEDAS (erMEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthy Plant‐Based Diet Index (HPDI), Unhealthy Plant‐Based Diet Index (UPDI), and Western Diet Score (WESTDIET). Healthy patterns (erMEDAS, MEDAS, DASH, HPDI) were associated with 22, 28, 24, and 16 genera, of which 82%, 75%, 79%, and 88% showed a protective profile (more abundant with lower, or less abundant with higher, depressive symptoms). UPDI and WESTDIET were associated with 20 and 27 genera, but only 25% and 26% were protective. Mediation analyses indicated that gut microbiota mediated the associations of MEDAS (ACME = –0.066, p = 0.006) and erMEDAS (ACME = –0.029, p = 0.011) with depressive symptoms. This study is among the first to test whether diet shapes a microbiota signature that mediates the diet–depression relationship, adding mechanistic insight into diet–mental health research.

Healthy dietary patterns are associated with gut microbial genera linked to lower depressive symptoms. In 644 older adults from the PREDIMED‐Plus cohort, 16S rRNA sequencing and dietary scoring revealed that taxa associated with a better diet quality were also more abundant in individuals with fewer depressive symptoms. Mediation analysis showed that gut microbiota significantly mediates the link between Mediterranean diet adherence and depression scores. These findings highlight a potential microbiome‐driven pathway connecting diet and mental health.