Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome
S. Brushett,
R. Gacesa,
A. Vich Vila,
M.F. Brandao Gois,
S. Andreu-Sánchez,
J.C. Swarte,
M.A.Y. Klaassen,
V. Collij,
T. Sinha,
L.A. Bolte,
J. Wu,
M. Swertz,
M.L.A. de Kroon,
S.A. Reijneveld,
C. Wijmenga,
R.K. Weersma,
J. Fu,
H.M. van Loo,
A. Kurilshikov,
A. Zhernakova
Affiliations
S. Brushett
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
R. Gacesa
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
A. Vich Vila
Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium
M.F. Brandao Gois
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
S. Andreu-Sánchez
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
J.C. Swarte
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
M.A.Y. Klaassen
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
V. Collij
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
T. Sinha
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
L.A. Bolte
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
J. Wu
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
M. Swertz
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
M.L.A. de Kroon
Department of Health Sciences, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
S.A. Reijneveld
Department of Health Sciences, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
C. Wijmenga
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
R.K. Weersma
Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
J. Fu
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
H.M. van Loo
Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
A. Kurilshikov
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
A. Zhernakova
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
ABSTRACTThe gut microbiome is involved in the bi-directional relationship of the gut – brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut – brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.
