Gut Microbiota Can Drive Neuroinflammation in Major Depressive Disorder

The influence of gut microbiota extends to the brain via neuroinflammation, resulting in changes in mood, cognitive function, anxiety, and other symptoms associated with major depressive disorder (MDD), according to a recent review article published in the European Journal of Neuroscience.

Previous studies in human and animal models suggest a relationship between gut microbiota and symptoms associated with MDD. The researchers reviewed studies on the relationship between gut microbiota and brain function to determine the extent of the relationship. 

The gut microbiota is thought to influence MDD through inflammatory processes, primarily the gut-brain axis.¹ Mice treated with the probiotic Bifidobacterium adolescentis showed a reversal of neuroinflammation and depressive symptoms.² Recent advances in neuroscience link chemokines to neurobiological processes driving psychiatric disorders. Experimental evidence links changes in the chemokine network to depressive behavior, and researchers of clinical studies indicated an association between neuroinflammation and MDD.³ As a result of these findings, there is growing interest in the use of anti-inflammatory agents in the treatment of MDD,⁴ and some investigators indicated improved antidepressant treatment effects.⁵

The gut microbiota is an important bidirectional pathway between the gut and the brain, and the communication between the gut and the brain is substantiated by the comorbidity between gastrointestinal and neurodegenerative diseases such as Parkinson disease⁶ and mood disorders, including MDD. Gut bacteria are essential in regulating brain development and function. Stress can dysregulate gut microbiota and stimulate proinflammatory cytokines.⁷ Probiotics influence gut microbiota and can indirectly influence neurological and psychiatric disorders. Researchers further indicate that imbalances in gut microbiota can allow increased permeability of the blood-brain barrier (BBB), and excessive production of inflammatory cytokines can pass the BBB and reach the brain resident cells. Microglial activation and inflammasome activation can be reduced by prebiotic treatment of gut microbiota, according to researchers, suggesting a possible treatment for age-related neuroinflammatory diseases.

Probiotics influence gut microbiota and can indirectly influence neurological and psychiatric disorders, according to researchers.

Both Lactobacillus and Bifidobacterium in general have been shown to limit the effects of neurological disorders.⁸ Oral injection of Bifidobacterium resulted in increased resilience to defeat stress in mice. Imbalances in gut microbiota can allow increased permeability of the BBB, and excessive production of inflammatory cytokines such as interleukin (IL)-1a, IL-1b, TNF-a, and IL-6,⁹ could pass the BBB and reach the brain resident cells, where they act on receptors expressed by neurons and glial cells.¹⁰ Microglial activation can be reduced by prebiotic treatment, suggesting a possible treatment for age-related neuroinflammatory diseases though reduction of monocyte infiltration into the brain.¹¹ Finally, according to researchers, the gut microbiota is related to the regulation of the kynurenine pathway, which plays an important role in the development of psychiatric disorders, including schizophrenia. Gut metabolites such as short-chain fatty acids can promote the production of serotonin from tryptophan, thus preventing typtophan conversion to the kynurenine pathway.¹²

The role of dysregulation of the gut-microbiota-brain axis is evident in MDD from animal and human studies, according to investigators. The authors concluded that “changes in these glial cells influence brain networks involved in memory, learning, emotions, and mood regulation, what could be behind the onset of depressive symptoms or anxiety.”¹

Disclosures: Several study authors declared associations with the pharmaceutical industry. Please see the original references for a full list of authors’ disclosures.

References

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2. Guo Y, Xie JP, Deng K, et al. Prophylactic effects of Bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: a role of the gut microbiota-inflammation axis. Front Behav Neurosci.  doi: 10.3389/fnbeh.2019.00126

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11. Boehme M, van de Wouw M, Bastiaanssen TFS, et al. Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome [published online May 16, 2019]. Mol Psychiatry. doi: 10.1038/s41380-019-0425-1

12. Reigstad CS, Salmonson CE, Rainey JF, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on the enterochromaffin cells. FASEB J. 2015;29:1395-1403.

This article originally appeared on Psychiatry Advisor