Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

Abstract

The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.

Keywords: Microbiota; blood-brain barrier; gut-brain axis; metabolites.

Figure 1.

Schematic representation of the human blood-brain-barrier neurovascular-endothelial-unit in health (a) and disease (b) states. Increased permeability related to, for example trauma or infection, is associated with disruption of endothelial tight junctions leading to the ingress and translocation of blood-borne immune cells, and inflammatory mediators such as cytokines and microbes and their products that can activate microglia, resulting in local inflammation leading to loss of extracellular matrix and astrocyte, pericyte and neuronal cell dysfunction and death.

Figure 2.

Pathways of communication along the gut-microbiota-brain axis. A complex interplay of epithelial, immune and neural cell signalling networks is involved in sensing and communicating changes in microbial metabolites in the gut and the brain involving both circulatory and neural routes.