Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations

Sharmili Edwin Thanarajah^{1

2

3

4}, Adèle H Ribeiro⁵, Jaehyun Lee^{1

4}, Nils R Winter⁶, Frederike Stein^{7

8}, Rachel N Lippert^{9

10

11}, Ruth Hanssen^{2

9

12}, Carmen Schiweck^{1

4}, Leon Fehse⁵, Mirjam Bloemendaal¹, Mareike Aichholzer^{1

4}, Aicha Bouzouina^{1

4}, Carmen Uckermark^{1

4}, Marius Welzel⁵, Jonathan Repple^{1

4

6}, Silke Matura¹, Susanne Meinert^{6

13}, Corinna Bang¹⁴, Andre Franke¹⁴, Ramona Leenings⁶, Maximilian Konowski⁶, Jan Ernsting⁶, Lukas Fisch⁶, Carlotta Barkhau⁶, Florian Thomas-Odenthal^{7

8}, Paula Usemann^{7

8}, Lea Teutenberg^{7

8}, Benjamin Straube^{7

8}, Nina Alexander^{7

8}, Hamidreza Jamalabadi⁷, Igor Nenadic^{7

8}, Andreas Lügering¹⁵, Robert Nitsch¹³, Sarah Kittel-Schneider^{16

17

18}, John F Cryan^{17

19}, Andreas Reif^{1

3}, Tilo Kircher^{7

8}, Dominik Heider^{5

20}, Udo Dannlowski^{6

21}, Tim Hahn⁶

Affiliations

¹ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt-Goethe University, Frankfurt am Main, Germany.
² Max Planck Institute for Metabolism Research, Cologne, Germany.
³ Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
⁴ Cooperative Brain Imaging Center (CoBIC), Goethe University Frankfurt, Frankfurt, Germany.
⁵ Institute of Medical Informatics, University of Münster, Münster, Germany.
⁶ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁷ Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany.
⁸ Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University, Giessen, Germany.
⁹ Department of Neurocircuit Development and Function, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany.
¹⁰ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
¹¹ NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹² Policlinic for Endocrinology, Diabetology and Preventive Medicine (PEPD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹³ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
¹⁴ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
¹⁵ MVZ Portal 10, Center for Liver, Stomach and Intestinal Diseases, Münster, Germany.
¹⁶ Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
¹⁷ APC Microbiome, University College Cork, Cork, Ireland.
¹⁸ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
¹⁹ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
²⁰ T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
²¹ Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Bielefeld, Germany.

PMID: 40991280
PMCID: PMC12461599 (available on 2026-09-24)
DOI: 10.1001/jamapsychiatry.2025.2579

Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations

Sharmili Edwin Thanarajah et al. JAMA Psychiatry. 2025.

. 2025 Sep 24:e252579.

doi: 10.1001/jamapsychiatry.2025.2579. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt-Goethe University, Frankfurt am Main, Germany.
² Max Planck Institute for Metabolism Research, Cologne, Germany.
³ Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
⁴ Cooperative Brain Imaging Center (CoBIC), Goethe University Frankfurt, Frankfurt, Germany.
⁵ Institute of Medical Informatics, University of Münster, Münster, Germany.
⁶ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁷ Department of Psychiatry and Psychotherapy, Marburg University, Marburg, Germany.
⁸ Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University, Giessen, Germany.
⁹ Department of Neurocircuit Development and Function, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany.
¹⁰ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
¹¹ NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹² Policlinic for Endocrinology, Diabetology and Preventive Medicine (PEPD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹³ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
¹⁴ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
¹⁵ MVZ Portal 10, Center for Liver, Stomach and Intestinal Diseases, Münster, Germany.
¹⁶ Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
¹⁷ APC Microbiome, University College Cork, Cork, Ireland.
¹⁸ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
¹⁹ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
²⁰ T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
²¹ Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Bielefeld, Germany.

PMID: 40991280
PMCID: PMC12461599 (available on 2026-09-24)
DOI: 10.1001/jamapsychiatry.2025.2579

Abstract

Importance: Soft drink consumption is linked to negative physical and mental health outcomes, but its association with major depressive disorder (MDD) and the underlying mechanisms remains unclear.

Objective: To examine the association between soft drink consumption and MDD diagnosis and severity and whether this association is mediated by changes in the gut microbiota, particularly Eggerthella and Hungatella abundance.

Design, setting, and participants: This multicenter cohort study was conducted in Germany using cross-sectional data from the Marburg-Münster Affective Cohort. Patients with MDD and healthy controls (aged 18-65 years) recruited from the general population and primary care between September 2014 and September 2018 were analyzed. Data analyses were conducted between May and December 2024.

Main outcomes and measures: Primary analyses included multivariable regression and analysis of variance (ANOVA) models examining the association between soft drink consumption and MDD diagnosis and symptom severity, controlling for site and education, and Eggerthella and Hungatella abundance, controlling for site, education, and library size. Mediation analyses tested whether microbiota abundance mediated the soft drink-MDD link.

Results: A total of 405 patients with MDD (275 female patients [67.9%]; mean [SD] age, 36.37 [13.33] years) and 527 healthy controls (345 female controls [65.5%]; mean [SD] age, 35.33 [13.13] years) were included. Soft drink consumption predicted MDD diagnosis (odds ratio [OR], 1.081; 95% CI, 1.008-1.159; P = .03) and symptom severity (P < .001; partial η2 [ηp2], 0.012; 95% CI, 0.004-0.035), with stronger effects in women (diagnosis: OR, 1.167; 95% CI, 1.054-1.292; P = .003; severity: P < .001; ηp2, 0.036; 95% CI, 0.011-0.062). In women, consumption was linked to increased Eggerthella (P = .007; ηp2, 0.017; 95% CI, 0.0002-0.068), but not Hungatella abundance. Mediation analyses confirmed that Eggerthella significantly mediated the soft drink-MDD association (diagnosis: P = .011; severity: P = .005), explaining 3.82% and 5.00% of the effect, respectively.

Conclusions and relevance: In this cohort study, it was found that soft drink consumption may contribute to MDD through gut microbiota alterations, notably involving Eggerthella. Public health strategies to reduce soft drink intake may help mitigate depression risk, especially among vulnerable populations; in addition, interventions for depression targeting the microbiome composition appear promising.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Edwin Thanarajah reported advisory board fees from Janssen during the conduct of the study. Dr Hanssen reported nonfinancial support and personal fees from Novo Nordisk and Rhythm Pharmaceuticals outside the submitted work. Dr Aichholzer reported personal fees from Johnson & Johnson Innovative Medicine/Janssen-Cilag GmbH during the conduct of the study. Dr Repple reported personal fees from Hexal, Janssen, Neuraxpharm, and Novartis outside the submitted work. Dr Straube reported grants from the German Research Foundation (DFG, project number STR1146/18-1) during the conduct of the study. Dr Nenadić reported grants from DFG (grants NE2254/1-2, NE2254/2-1, NE2254/3-1, and NE2254/4-1) during the conduct of the study. Dr Kittel-Schneider reported personal fees from Janssen, Medice, and Takeda Pharmaceutical Company outside the submitted work. Dr Cryan reported personal fees from Bromtech and Yakult and grants from Danone Nutricia and Nestle outside the submitted work. Dr Reif reported personal fees from AbbVie, Boehringer Ingelheim, Compass, GH Research, Johnson & Johnson, LivaNova, Medice, MSD, Newron, SAGE/Biogen, and Shire/Takeda Pharmaceutical Company outside the submitted work. Dr Kircher reported unrestricted educational grants from Aristo, Johnson & Johnson, Otsuka, and ROVI outside the submitted work. Dr Dannlowski reported grants from DFG during the conduct of the study. No other disclosures were reported.

References

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Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations

Affiliations

Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources