Harnessing Gut Microbes for Mental Health: Getting From Here to There

Abstract

There has been an explosion of interest in the study of microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology. Accumulating data suggest that altered communication between gut microbiota and host systems could participate in disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The conceptual development of the microbiome-gut-brain axis has facilitated understanding of the complex and bidirectional networks between gastrointestinal microbiota and their host, highlighting potential mechanisms through which this environment influences central nervous system physiology. Communication pathways between gut microbiota and the central nervous system could include autonomic, neuroendocrine, enteric, and immune systems, with pathology resulting in disruption to neurotransmitter balance, increases in chronic inflammation, or exacerbated hypothalamic-pituitary-adrenal axis activity. However, uncertainty remains regarding the generalizability of controlled animal studies to the more multifaceted pattern of human pathophysiology, especially with regard to the therapeutic potential for neuropsychiatric health. This narrative review summarizes current understanding of gut microbial influence over physiological function, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis. Experimental and clinical data regarding means of therapeutic manipulation of gut microbiota as a novel treatment option for mental health are described, and important knowledge gaps are identified and discussed.

Keywords: Depression; Gut dysbiosis; Gut-brain axis; Mental health; Microbiota transplant; Probiotics.

Figure 1. Schematic diagram showing the four major pathways of potential information transfer from the maternal gut microbiome to the brain and behavior of offspring

(1) Metabolites shaped by the maternal microbiome may enter the fetal circulation and affect early neurodevelopment of the fetus during gestation. (2) Metabolites shaped by the maternal microbiome contained in the milk may be ingested by offspring during lactation. (3) Maternal microbiota could affect mothering behavior via the mother’s brain during the early neonatal period. (4) Maternal microbiota could be directly vertically transferred to offspring at birth, and reinforced through coprophagia during the neonatal period. In addition, there are complex interactions between the microbiome, metabolome, immune system, brain, and behavior within offspring as shown in Fig. 2.

Figure 2. Signaling pathways between maternal gut microbiota and behavior

Schematic diagram showing potential signaling pathways through which the gut microbiome can affect metabolic and mental health. In the intestinal lumen, microbiota, food, bile acids, and mucosal factors interact with each other. The intestinal mucosa then propagates information to other organs including the brain through the blood circulation and sensory nerves. In turn, the brain can affect the mucosa and eventually gut microbiota directly or indirectly (via other organs) through changes in autonomic nervous system (ANS) and endocrine outflow and through changes in food intake quantity and choice.