The microbiota-gut-brain axis in stress and depression

Abstract

Humans and animals are evolved to have instinctive physiological responses to threats. The perception of threat by the brain triggers a multitude of changes across the brain and body. A large body of research have demonstrated that our hardwired survival instinct, the stress response, can become maladaptive and promote major depressive disorders and other neuropsychiatric impairments. However, gaps in our understanding of how chronic stress contributes to depression and mental disorders suggest that we also need to consider factors beyond the biology of the host. The unravelling of the structure and function of microorganisms that humans and animals are host to have driven a paradigm shift in understanding the individual as a collective network composed of the host plus microbes. Well over 90% of bacteria in the body reside in the large intestines, and these microbes in the lower gut function almost like an organ in the body in the way it interacts with the host. Importantly, bidirectional interactions between the gut microbiota and the brain (i.e., the two-way microbiota-gut-brain axis) have been implicated in the pathophysiology of mental disorders including depression. Here, in summarizing the emerging literature, we envisage that further research particularly on the efferent brain-gut-microbiota axis will uncover transformative links in the biology of stress and depression.

Keywords: brain-gut axis; depression; host–microbe interactions; microbiome; microbiota-gut-brain connection; mindfulness; perception; stress.

Figure 1

The afferent gut-to-brain axis. Microbial peptides and metabolites interact with peripheral receptors and modulate ascending sensory neurons through vagal and spinal pathways, which then act on neural circuits in the brain. Humoral factors may also enter the brain to modulate function of neurons and glia. Gut dysbiosis, characterised by unfavourable alterations of the gut microbial biochemistry, perturbs physiological gut-brain communication and causes diseases.

Figure 2

The efferent brain-to-gut axis. The brain controls the gut microbiota through neural and endocrinal pathways. Descending signals to the intestinal epithelium regulate goblet cells which produce mucin, enteroendocrine cells which secrete various peptides, Paneth cells which release anti-microbial compounds, and plasma cells which produce antibodies. These compounds from the host may promote or inhibit the growth of microbes in the gut and influence biochemical pathways of the microbiota.