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. 2023 Dec;15(2):2281360.
doi: 10.1080/19490976.2023.2281360. Epub 2023 Nov 28.

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome

S Brushett  1   2 , R Gacesa  1   3 , A Vich Vila  4   5 , M F Brandao Gois  1 , S Andreu-Sánchez  1   6 , J C Swarte  1   3 , M A Y Klaassen  1   3 , V Collij  1   3 , T Sinha  1 , L A Bolte  1   3 , J Wu  1 , M Swertz  1   7 , M L A de Kroon  2 , S A Reijneveld  2 , C Wijmenga  1 , R K Weersma  3 , J Fu  1   6 , H M van Loo  8 , A Kurilshikov  1 , A Zhernakova  1
Affiliations

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome

S Brushett et al. Gut Microbes. 2023 Dec.

Abstract

The 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.

Keywords: dysthymia; generalized anxiety disorder; gut microbiome; gut-brain axis; internalizing disorders; major depressive disorder; psychotropic drugs.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Schematic of study design.
Figure 2.
Figure 2.
Bacterial species associated with internalizing disorders and psychotropic drugs.
Figure 3.
Figure 3.
Bacterial species associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.
Figure 4.
Figure 4.
Bacterial gut – brain modules associated with internalizing disorders and psychotropic drugs.
Figure 5.
Figure 5.
Bacterial gut – brain modules associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.
See this image and copyright information in PMC

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