Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis

Abstract

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

Keywords: behavior; brain injury; gut bacteria; host genes; immunity.

FIGURE 1

The bi-directional microbiome-gut-brain axis in health and disease. (A) Brain dysfunction may lead to the disruption of brain-to-gut-to-microbiome signals, host behaviors and dietary habits that ultimately affect the normal colonization of the gut microbiome. Host genes may influence intestinal function and the microenvironment which may then impact on the structure/composition of the microbiome. The origins of brain disorders may be also linked to host genetics. A pre-existing abnormality in the gut microbiome may lead to heightened inflammation and cause disruption of the gut-to-brain communication, aggravating brain dysfunction. (B) Normalizing microbial community structure and function would augment host immunity and improve metabolism that would counter-balance the detrimental effects of brain dysfunction, in spite of dysbiosis not being the primary site of pathology. Rehabilitation of brain pathology would normalize brain-to-gut-to-microbiome signals and lead to a diminished inflammatory response, contributing to the improvement of the gut community. However, current treatments have side-effects that may include a disruption of the gut microbiome and normal gut health.