Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience

Abstract

Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health.

Keywords: Central nervous system; Depression; Endocrine system; Immune system; Inflammation; Microbiome; Microbiome-gut-brain axis; Microbiota; Prebiotics; Probiotics.

Figure 1.

Illustration of reviewed bidirectional communication between the central nervous system, endocrine system, and immune system and the microbiome, which contribute to depression.

Figure 2.

Diagram showing where in the rodent body each reviewed article focused. Red circles indicate an immune study, green circles indicate an endocrine study, and blue circles indicate a study involving the central nervous system. Circles with two different colored rings indicate measurements from both systems represented by those colors. Red text indicates that the direction measured was from the microbiome to the system, and blue text indicates that the direction was from the system to the microbiome. Numbers listed in the figure correspond to Table 1.

Figure 3.

Diagram showing where in the human body each reviewed article focused. Red circles indicate an immune study, green circles indicate an endocrine study, and blue circles indicate a study involving the central nervous system. Circles with two different colored rings indicate measurements from both systems represented by those colors. Red text indicates that the direction measured was from the microbiome to the system, and blue text indicates that the direction was from the system to the microbiome. Numbers listed in the figure correspond to Table 1.

Figure 4.

Relevant aspects of tryptophan metabolism to articles reviewed. Five articles (numbers listed in the figure correspond to Table 1) explicitly looked at different aspects of tryptophan metabolism.