Advances in the Gut Microbiome and Mood Disorders

Sabrina Mörkl; Mary I. Butler; Sonja Lackner


Curr Opin Psychiatry. 2023;136(1):1-7. 

In This Article

Abstract and Introduction


Purpose of Review: The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022.

Recent Findings: Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation.

Summary: Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.


Western society's healthcare systems are amongst the most progressive systems in the world with high care standards. Nevertheless, chronic psychiatric disorders such as major depressive disorder (MDD) and bipolar disorder are on the rise. For example, in 2020, depression (MDD) affected 3152.9 people per 100 000 population globally with an additional 53.2 million people affected due to the Covid-19 pandemic (an increase of 27.6%).[1] An estimated 48.8 million people suffer from bipolar disorder, which is associated with an early disease onset accounting for 9.9 million years of life lived with disability worldwide.[2]

Despite enormous efforts to treat mood disorders, they remain a chronic condition and a leading cause of permanent disability.[3] Furthermore, 10–30% of individuals with depression suffer from treatment-resistant MDD, which is defined as a condition wherein at least two or more antidepressants, given at an adequate dose for an adequate duration, failed to have an effect.[4,5] In addition, psychopharmacological treatment often targets symptoms of neurotransmitter imbalance while ignoring other underlying molecular backgrounds of affective disorders such as disturbed circadian rhythms, low-grade inflammation and oxidative stress.[6–8] Inflammatory depression, for example, presents specific clinical correlates and biological underpinnings.[9]

Recent advances in research demonstrate a close link between mood disorders and the gut microbiome. The microbiota-gut-brain-axis (MGBA), a bidirectional signalling system, ensures a continuous flow of information between the gut microbiota, its metabolites, the brain and vice versa. The mechanisms of signal transmission from bacteria to the brain are not yet fully understood and include neural, immune, metabolic and endocrine pathways. Furthermore, the gut microbiome itself, the integrity of the intestinal lining and the function of the vagal nerve seem to be relevant for inflammatory processes in the pathophysiology of mood disorders.[10]

Initial research indicated that the gut microbiome in rodent models of depression was altered; this has then been replicated in clinical studies.[11] Mechanistically, depressive behavioural features could also be transferred to rodents, following a faecal microbiota transplant (FMT) from depressed individuals, along with alterations in tryptophan metabolism and immune status.[12] This is of major relevance, as the integrity and function of the gut microbiome and its metabolites act as epigenetic regulators in gene-environment interactions.[13]

This narrative review aims to highlight advances in gut microbiome research concerning mood disorders by discussing clinical studies, randomized controlled trials and meta-analyses, which were published between 2021 and 2022.[]