Soft Drinks, Gut Bacteria, and Depression: New Evidence from JAMA Psychiatry

A recent cohort study published in JAMA Psychiatry found that higher intake of soft drinks is associated with increased risk of major depressive disorder (MDD) and more severe symptoms, and that this risk is partly mediated by changes in the gut microbiome.

Study Design and Key Findings

The study, led by Sharmili Edwin Thanarajah and colleagues, recruited individuals diagnosed with major depressive disorder and healthy controls. Using self-reported soft drink consumption and stool microbiome analyses, the investigators examined whether alterations in gut bacterial taxa could explain the association between soft drink intake and depression.

They found that in women, higher soft drink consumption correlated with a 16.7% increased risk of having MDD, along with greater symptom severity. The researchers identified Eggerthella (a bacterial genus) as being more abundant in women with high soft drink intake. This taxon explained 3.8% of the effect of soft drink intake on MDD diagnosis and 5.0% of the effect on symptom severity in mediation analyses. After adjusting for body mass index (BMI), antidepressant use, and total calorie intake, these associations remained statistically significant.

In men, however, the study did not find a significant association between soft drink consumption, microbiome changes, and depression.

In the authors’ conclusions, they note that the results support the possibility that soft drink–induced microbiome changes may contribute to depression risk, particularly in women, and suggest that public health strategies to reduce soft drink consumption might help mitigate depression incidence.

Mechanisms and Biological Plausibility

The connection between gut microbes and mood is increasingly studied under the “gut-brain axis” framework. The gut microbiome influences immune, metabolic, and neural signaling pathways, which can affect brain function.

Excessive sugar in soft drinks may overwhelm the small intestine’s capacity and shift microbial composition toward taxa with pro-inflammatory properties. In this study, higher soft drink intake was associated with elevated Eggerthella counts, a genus previously linked to inflammation and metabolic changes.

In experimental contexts, Eggerthella has been associated with reduced butyrate production, a short-chain fatty acid with anti-inflammatory and gut-barrier–protecting functions. Depletion of butyrate could contribute to systemic inflammation and disruption in neurotransmitter pathways, including serotonin, which may increase vulnerability to depression.

Moreover, sugar spikes from soft drinks could foster insulin and stress-hormone fluctuations, compounding the microbial impact on mood regulation.

Strengths, Limitations, and Next Steps

A strength of the study is its attempt to mediate the association between soft drinks and depression through microbiome analysis, giving a mechanistic insight rather than just correlation.

However, the effects mediated by Eggerthella are modest (only a few percent), meaning much of the association remains unexplained by the microbiome taxa measured. The observational design also limits causal inference. Confounding factors, reverse causation (depressed mood leading to higher soft drink intake), or unmeasured dietary and lifestyle variables may influence results.

Furthermore, the stronger association in women may reflect hormonal, behavioral, or microbiome-sex interactions (sometimes called the “microgenderome”).

Future research should include randomized controlled trials, longitudinal designs, and deeper microbiome profiling to explore causality and test interventions (e.g., probiotic or dietary modifications) to modify depression risk.

Implications for Public Health and Clinical Practice

Given how common soft drink consumption is globally, even a modest risk increment could have large population health implications.

Clinicians and mental health professionals may consider screening dietary patterns in patients with depressive symptoms. Dietary counseling to reduce consumption of sugar-sweetened beverages could be a low-cost adjunctive strategy.

In research and intervention programs, targeting gut microbiome health through diet, prebiotics, probiotics, and fiber intake holds promise in preventive mental health strategies.

Reference

1. Thanarajah, Sharmili Edwin, et al. “Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations.” JAMA Psychiatry. September 24, 2025. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2839019

(Rh/Eth/TL/MSM)