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expert reaction to study on association between soft drink consumption and depression mediated by gut microbiome

A study published in JAMA Psychiatry looks at an association between soft drink consumption and depression mediated by gut microbiome changes. 

 

Dr Rachael Rigby, Senior lecturer in Biomedical and Life Sciences, Lancaster University, said:

“Diet is one of the main influencers of the gut microbiota composition. This article focuses on the impact of sugary soft drinks (SSB, defined as ultra-processed, calorie-dense, and rich in simple sugars like glucose and fructose).  Other diets such as those low in soluble-fibre1, high in artificial sweeteners2 and high in fat3, also lead to the promotion the growth of specific bacterial genera, a phenomenon described as dysbiosis. The altered growth of gut bacteria is associated with numerous physiological systems, including but not limited to: insulin resistance, inflammation and depression. Increasing evidence suggests a causal role of dysbiosis in depression4, with potential mechanisms being investigated.  Eggerthella and Hungatella are genera of bacteria that synthesize chemicals5 such as glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters influencing depression. If levels of neurotransmitters are disrupted, mental health is likely to be affected.

“In this study 405 participants with major depressive disorder (MDD) and 527 healthy controls were studied. Consumption of SSB was linked to increased Eggerthella, but not Hungatella abundance, supporting previous data6 that SSB promote gut dysbiosis. The fact that previous data7 has suggested similar bacteria changes linked to SSB intake, reporting reduced levels of genus Lachnobacterium and increasing the Firmicutes:Bacteroidetes ratio, adds validity to these findings.  

“Whilst this mechanism8 is attractive, one must consider whether we’re looking at cause or effect, i.e. did the bacterial changes (due to increased SSB consumption) or the depression come first?  Did participants, presenting with MDD, drink more soft drinks to cheer themselves up/ provide energy and thus retrospectively induce the bacteria changes?  Of note, the MDD participants had lower levels of education, representing a confounding variable which may contribute to MDD and ostensibly promote SSB consumption.  Relatively speaking the impact of SSB on depression may not be the whole story, but the fact that statistical significance was achieved, despite so many other lifestyle variables is very interesting.

“Even more interestingly, these effects were only significant in female and not male participants.  This may be due to slightly higher female participant number, or the influence of sex hormones exacerbating the impact of SSB.  Sex-specific mechanisms remain unclear, but highlight the need to do statistically-powered research in both sexes.”

1 https://pubmed.ncbi.nlm.nih.gov/37513676/

2 https://doi.org/10.1093/advances/nmy037

3 https://doi.org/10.1371/journal.pone.0012191

4 https://doi.org/10.1016/j.ebiom.2023.104527

5 https://www.nature.com/articles/s41467-022-34502-3

6 https://doi.org/10.1371/journal.pone.0012191

7 https://pubmed.ncbi.nlm.nih.gov/33030577/

8 http://10.0.13.62/cells11081362

 

Prof Ciara McCabe, Professor of Neuroscience, Psychopharmacology and Mental Health, University of Reading, said:

“I find a lot of these association studies misleading. This study does not prove that drinking soft drinks causes depression or increased severity of depression. Simply, those with depression could drink more soft drinks. 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”

“When someone feels depressed, they change their behaviour including eating patterns which could explain increased soda drinking not the other way round.”

 

Dr Guillaume Meric, Associate Professor at the Department of Life Sciences, University of Bath, said:

“The study contributes to the idea that soft drinks consumption and depression often show up together, especially in women, and highlights a gut bacterium called Eggerthella as a possible link. It does not robustly show or imply that these drinks cause depression, and the observed role of the microbiome looks small. If you drink a lot of soft drinks, cutting back is low-risk and likely helpful overall, but this study does not at all mean that this is a stand-alone treatment for depression.”

 

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes, good quality for this type of observational, cross-sectional microbiome-epidemiology study. There is a solid cohort recruitment in terms of numbers (less so in terms of diversity, likely a very European-focused cohort from Germany), reasonable adjustments, sensitivity checks, transparent limits. But as for many high-quality microbiome studies, it cannot establish causation for sure, and effects are modest. The associations are well supported; 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. The lack of diversity in the patients enrolled (probably mainly a European cohort) also prevents from scaling up observations to humans in general. The microbiome part could also be better characterized (with shotgun metagenomics for instance, instead of a 16S-based sequencing approach).”

 

How does this work fit with the existing evidence?

“Consistent with prior epidemiology linking sugary drinks and depression. It furthers it with clinical diagnosis and a microbiome angle involving Eggerthella, which has been linked to various other conditions and dietary patterns. A promising player to investigate further.”

 

What are the implications in the real world?  Is there any overspeculation?

“Cutting back on soft drinks is sensible for many reasons, and this paper suggests a possible (small) mental-health upside, especially for women. Policy implications for depression alone are premature based only on this study but it is promising work for more investigations.”

 

Could it also be an inverse association where people with MDD are more likely to drink more fizzy drinks?

“Reverse or bidirectional links (MDD -> more soft drinks) are also plausible and explicitly acknowledged in the paper. Only randomized or longitudinal, well-adjusted studies can clarify direction, and even then, microbiome mechanisms and implication would also need better functional confirmation.”

 

Professor Debbie Shawcross, Professor of Hepatology & Chronic Liver Failure, and Dr Victoria Kronsten, MRC Doctoral Research Fellow, The LIMBIC Lab, Kings College London, said:

“This multi-centre clinical study has found a possible link between soft drink consumption and depression. Women who drank more soft drinks were more likely to be diagnosed with depression and to report more severe symptoms. However, no effect was found in male participants.

“Importantly, the research also found changes in gut bacteria linked to soft drink consumption. Women who consumed more soft drinks had increased levels of Eggerthella — a type of gut bacteria previously associated with depression — and reduced microbiome diversity. Further analysis suggested that Eggerthella may partially explain the link between soft drinks and depression, even after controlling for calorie intake and other factors.

“The study is one of the first to explore this connection in patients with clinically diagnosed depression and to account for key confounding factors such as body mass index (BMI), education, calorie intake, and medication use.

“While the effects observed were modest, they are considered meaningful because soft drink consumption is a modifiable risk factor — and women appear more biologically sensitive to its impact.

“It is important to note that establishing causation in dietary studies is difficult. Depression itself may lead to increased intake of sugary foods and drinks. However, the findings support growing evidence that diet and gut health may play a role in mental health.”

“While this paper does not provide enough evidence alone to support public health changes in soft drink consumption specifically to mitigate depression like the authors have suggested, there are many other reasons to introduce measures to curb sugary soft drinks for other reasons too as it is contributing a global epidemic of obesity, diabetes and liver disease.”

 

Prof Andrew McQuillin, Professor of Molecular Psychiatry, University College London (UCL), said:

“The way that the manuscript is written suggests that the authors have demonstrated a causal relationship whereas in the discussion they clearly state that there is no evidence for a causal relationship and indeed that the reverse may be true in that people with depression or depressive symptoms are more prone to consume soft drinks.

“One of the most worrying statements in the paper is “Education, prevention strategies, and policies aiming to reduce soft drink consumption are urgently required to mitigate depressive symptoms.” This statement assumes that the authors have found strong and reproducible evidence for soft drink consumption leading to depression. The evidence is not strong enough to be supporting a statement like this.

“There are many potential confounders for the relationship observed. How do socio economic status and the levels of educational attainment differ between the depression and control groups?  Why when the data is broken down by sex is the effect only seen in females?

“Other limitations include that the effect sizes reported are very small with wide confidence intervals and the findings have not been replicated in an independent study.”

 

Dr Stephen Burgess, Statistician at the MRC Biostatistics Unit, University of Cambridge, said:

“This is an observational analysis, and so it is limited in the extent to which it can make causal claims. It finds that individuals who consume soft drinks have higher risk of depression than those who do not. It cannot make any claim about whether soft drink consumption is responsible for this elevated risk, as opposed to other factors that differ between soft drink consumers and non-consumers. Even taking the study’s findings at face value, soft drink consumers are only at slightly higher risk of depression than non-consumers, with the study showing an 8% relative difference in depression risk. Such a difference is not much more than would be expected by chance alone if you divided the study participants into two arbitrary groups at random – it is likely that one group would have slightly higher levels of depression than the other. It is entirely possible that this association is a chance finding.

“Puzzlingly, the researchers have more statistical confidence in one specific component of the microbiome being the factor explaining the difference in risk between soft drink consumers and non-consumers than they do that there is any difference in risk between soft drink consumers and non-consumers in the first place. This finding does not pass even a cursory sense check – we cannot have a high degree of confidence in a factor being the reason for a difference in risk if we do not have high confidence that there is a difference in risk. We cannot be confident based on this study that there even is a relevant difference in depression risk between soft drink consumers and non-consumers. Even less can we be confident that soft drink consumption is the factor causing this difference. And less still can we be confident that this difference (if it exists) has anything to do with the gut microbiome.”

 

 

Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations’ by Sharmili Edwin Thanarajah  et al. was published in JAMA Psychiatry at 16:00 UK time on Wednesday 24 September 2025. 

 

DOI: 10.1001/jamapsychiatry.2025.2579

 

 

Declared interests

Dr Rachael Rigby: No declarations of interest

Dr Stephen Burgess: No relevant conflict of interest to declare.

Prof Ciara McCabe: Prof McCabe research is on investigating the causal mechanisms of depression. She also has examined the neural responses to sugars and sweeteners. She has been funded by the Medical Research Council (MRC), Natural Environmental Research Council (NERC), a University of Reading Research Fellowship, UKRI, The British Science Association (BSA) and industry collaborators such as GWPharma Ltd, EPC flavouring Ltd and Juneobiont PTE. Ltd.

For all other experts, no response to our request for DOIs was received.

 

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