Soft drinks may fuel depression via gut microbiome

Consumption of soft drinks predicts major depressive disorder (MDD) diagnosis and symptom severity in women through gut microbiota alterations, a cohort study has shown.

“Soft drink consumption is linked to negative physical and mental health outcomes, but its association with MDD and the underlying mechanisms remain unclear,” wrote the researchers.

In a multicentre cohort study conducted in Germany, researchers recruited 405 patients with MDD (mean age, 36.37 years; female, 67.9 percent) and 527 healthy controls (mean age, 35.33 years; female, 65.5 percent) from the general population and primary care from September 2014 to September 2018. [JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2025.2579]

MDD–soft drink association

Soft drink consumption predicted MDD diagnosis (odds ratio [OR], 1.081; 95 percent confidence interval [CI], 1.008–1.159; p=0.03) and symptom severity (p<0.001; partial η², 0.012; 95 percent CI, 0.004–0.035).

MDD is linked to increased emotional eating and preference for high-sugar food, which may lead to greater soft drink consumption. “Our findings underscore the importance of interrupting this vicious cycle, especially given the metabolic risks associated with both MDD and high soft drink consumption,” noted the researchers.

Women are vulnerable

“Our findings reveal a gender-specific association, with the link between soft drink consumption and depression being driven primarily by females [diagnosis: OR, 1.167; 95 percent CI, 1.054–1.292; p=0.003; symptom severity: p<0.001; partial η², 0.036; 95 percent CI, 0.011–0.062],” highlighted the researchers.

In contrast, no significant effect was observed in male participants in both MDD diagnosis (OR, 1.020; 95 percent CI, 0.924–1.127; p=0.69) and symptom severity (p=0.11; partial η², 0.008; 95 percent CI, 0.000–0.033).

“Sex hormones likely play a key role, but mechanisms remain unclear,” commented the researchers.

Mediated by Eggerthella

In the mediation analyses, the researchers examined microbiota data, specifically looking at the abundance of Eggerthella and Hungatella – two bacteria previously linked to MDD.

The researchers accounted for key confounding factors, such as body mass index, education, total calorie intake, and medication use, ensuring that the associations are not merely attributable to these variables.

Abundance of Eggerthella, but not Hungatella, significantly mediated the association between soft drinks and MDD in female participants (diagnosis: p=0.011; severity: p=0.005). However, no significant association was found in male participants.

“Excessive simple sugars in soft drinks disrupt the gut microbiome by fostering proinflammatory bacteria, weakening gut barrier integrity, and impairing mucosal immunity,” explained the researchers. “Soft drinks contain additives such as artificial sweeteners [eg, aspartame, saccharin] and preservatives [eg, benzoates, sorbates] that further disrupt gut microbial balance.”

The observed effects were small (diagnosis: 3.82 percent; severity: 5 percent). “However, mediation effects are valuable not because of their size, but because they can illuminate causal structure, inform further research on targeted interventions, and accumulate meaningfully across systems and populations,” added the researchers.

Public health strategies to reduce soft drink consumption may help decrease the risk of depression, particularly among vulnerable populations. Additionally, interventions targeting the microbiome composition may offer promise in depression management.