New study links soft drink consumption to depression via the gut microbiome

A new study suggests a connection between the consumption of soft drinks and major depressive disorder, potentially acting through alterations in the gut’s microbial community. The research, published in JAMA Psychiatry, identifies a specific bacterium that may play a part in this relationship, offering a new perspective on how dietary choices can influence mental health.

The human gut is home to trillions of microorganisms, collectively known as the gut microbiome. This internal ecosystem communicates with the brain through a complex network of signals, often called the gut-brain axis. The composition of these microbial communities can influence mood, behavior, and brain function. This connection has led researchers to explore how external factors, like diet, might impact mental health by first changing the gut environment.

Previous research has already connected soft drink consumption with a range of negative physical health outcomes. Separately, other studies have shown that the gut microbiomes of individuals with depression can differ from those without the condition. For instance, experiments involving the transfer of gut microbes from depressed human patients to rodents have induced behaviors in the animals that resemble anxiety and depression.

A large, collaborative team of researchers from institutions primarily in Marburg, Münster, and Frankfurt, Germany, sought to bring these lines of inquiry together. They aimed to investigate if there was a direct link between soft drink intake and diagnosed depression, and if the gut microbiome could be the biological mechanism explaining such a link.

To conduct their investigation, the researchers drew upon data from the Marburg-Münster Affective Disorders Cohort Study. This provided them with a large sample of 932 participants, which included 405 patients who had a clinical diagnosis of major depressive disorder (MDD) and 527 healthy control individuals. The two groups were comparable in age and sex distribution.

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Participants’ dietary habits were assessed using a detailed food frequency questionnaire. This tool asked them to report how often they consumed a standard portion of various foods and drinks, including soft drinks like lemonade and cola, over the past year.

To measure the severity of depressive symptoms, individuals completed the Beck Depression Inventory, a standardized self-report questionnaire. In addition, stool samples were collected from a subset of participants to analyze the composition of their gut microbiomes. The team used a genetic sequencing technique known as 16S ribosomal RNA analysis, which allows for the identification and quantification of different types of bacteria present in a sample.

The initial analysis examined the direct relationship between soft drink consumption and depression. The results showed that higher intake of soft drinks was associated with a diagnosis of MDD. This connection appeared to be driven primarily by female participants; in women, higher consumption was linked to an increased likelihood of having an MDD diagnosis, while no such effect was observed in men.

A similar pattern emerged when the researchers looked at symptom severity. In the entire sample, greater soft drink intake was associated with more severe depressive symptoms. When the data was separated by sex, this association remained strong for women but was not statistically significant for men. This sex-specific finding prompted the team to focus their subsequent microbiome analyses exclusively on the female participants.

“Our data suggests that the relation between soft drinks and depressive symptoms arises via the influence of the microbiome,” said Sharmili Edwin Thanarajah, the study’s lead author from the University Hospital Frankfurt and the Max Planck Institute for Metabolism Research in Cologne.

The next step was to see if soft drinks affected the gut microbiome in a way that could explain the link to depression. Building on previous work that identified two bacterial genera, Eggerthella and Hungatella, as being potentially related to MDD, the team tested whether soft drink consumption was associated with the abundance of these specific microbes.

They found that in women, higher soft drink intake was indeed linked to a greater abundance of Eggerthella. No such link was found with Hungatella. The analysis also revealed that higher soft drink consumption was associated with lower overall microbial diversity, which can be an indicator of a less resilient gut ecosystem.

With these pieces in place, the researchers performed a mediation analysis. This statistical method tests a hypothesized chain of events to see if the data is consistent with it. The proposed model was that soft drink consumption influences the abundance of Eggerthella, which in turn influences the risk and severity of depression.

The analysis supported this model for female participants. The abundance of Eggerthella was found to explain a small but statistically significant portion of the total effect of soft drink consumption on both MDD diagnosis (about 3.8%) and symptom severity (about 5.0%).

The researchers note that sugary drinks can disrupt the balance of the gut microbiome, favoring the growth of certain bacteria. “Changes in the microbiome can be influenced by diet and are therefore a potential therapeutic target,” explained Edwin Thanarajah. “Even small adjustments in consumer behavior might have a big impact, especially when considering the widespread consumption of soft drinks.”

While the study presents a detailed picture, it has several important limitations. As an observational study, it can identify associations but cannot prove that soft drink consumption causes depression. The relationship could be bidirectional. Ciara McCabe, a professor of neuroscience at the University of Reading who was not involved in the study, noted this point. “Simply, those with depression could drink more soft drinks,” McCabe told the Science Media Centre. “As the authors say themselves depression is associated with increased emotional eating and preference for high sugar food, which may lead to greater soft drink consumption.”

The proportion of the effect explained by the microbiome was also modest. Guillaume Meric, an associate professor at the University of Bath, commented on this aspect. “The microbiome mediation is statistically significant but explains only about 4–5% of the association, which makes it an interesting hypothesis to validate with further studies,” he said. The authors contend that even mediators with small effects can be meaningful in complex systems, as they might point toward pathways that are easier to modify.

Other experts pointed to potential confounding factors. Andrew McQuillin, a professor of molecular psychiatry at University College London, questioned the strength of the evidence. “The effect sizes reported are very small with wide confidence intervals and the findings have not been replicated in an independent study,” he remarked. The reliance on self-reported dietary information could also introduce inaccuracies.

Future research will be needed to untangle the direction of these relationships and confirm the findings. Randomized controlled trials, while challenging in dietary research, would provide stronger evidence of a causal link. Further investigation is also required to understand the sex-specific nature of the findings, which could involve hormonal differences or other biological factors.

Despite these caveats, the study adds to a body of evidence suggesting that diet is an important, modifiable factor in mental health. Rachel Lippert, a researcher from the German Institute of Human Nutrition Potsdam-Rehbrücke and a co-author of the study, sees potential in these findings.

“Microbiome-based approaches such as targeted nutritional therapies or probiotic strategies might help to effectively alleviate depressive symptoms in the future,” she said. The work suggests that public health strategies aimed at reducing soft drink intake could have benefits that extend beyond physical health to include mental well-being.

The study, “Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations,” was authored by Sharmili Edwin Thanarajah, Adèle H. Ribeiro, Jaehyun Lee, Nils R. Winter, Frederike Stein, Rachel N. Lippert, Ruth Hanssen, Carmen Schiweck, Leon Fehse, Mirjam Bloemendaal, Mareike Aichholzer, Aicha Bouzouina, Carmen Uckermark, Marius Welzel, Jonathan Repple, Silke Matura, Susanne Meinert, Corinna Bang, Andre Franke, Ramona Leenings, Maximilian Konowski, Jan Ernsting, Lukas Fisch, Carlotta Barkhau, Florian Thomas-Odenthal, Paula Usemann, Lea Teutenberg, Benjamin Straube, Nina Alexander, Hamidreza Jamalabadi, Igor Nenadić, Andreas Lügering, Robert Nitsch, Sarah Kittel-Schneider, John F. Cryan, Andreas Reif, Tilo Kircher, Dominik Heider, Udo Dannlowski, and Tim Hahn.