Microbiota and the control of blood-tissue barriers

Abstract

The gastro-intestinal tract is an ecosystem containing trillions of commensal bacteria living in symbiosis with the host. These microbiota modulate a variety of our physiological processes, including production of vitamins, absorption of nutrients and development of the immune system. One of their major functions is to fortify the intestinal barrier, thereby helping to prevent pathogens and harmful substances from crossing into the general circulation. Recently, effects of these microbiota on other blood-tissue barriers have also been reported. Here, we review the evidence indicating that gut bacteria play a role in regulating the blood-brain and blood-testis barriers. The underlying mechanisms include control of the expression of tight junction proteins by fermentation products such as butyrate, which also influences the activity of histone deacetylase.

Keywords: blood-brain barrier; blood-testis barrier; butyrate; intestinal barrier; microbiota; short chain fatty acids; tight junctions.

Figure 1.

The blood–brain barrier (BBB). Molecules cross the BBB either transcellulary or paracellularly between the cells through the junctions.

Figure 2.

Schematic illustration for the time-course of BBB development. Modified from ref. .

Figure 3.

The blood-testis barrier (BTB) is formed by tight junction protein between Sertoli cells.

Figure 4.

A simplified diagram illustrating the morphological differences between the blood‐testis barrier (BTB) and the blood‐brain barrier (BBB). (A) In the BTB, tight junctions (TJs) coexist with basal ectoplasmic specializations (ES), basal tubulobulbar complexes (TBC), and desmosome‐like junctions. (B) In the BBB TJs are restricted to the apical surface of the endothelium, sealing the intercellular space, with adherens junctions (AJ) located immediately below. Modified from ref. .

Figure 5.

Microbial impact on host physiology. Microbiota in the intestinal tract exerts profound effects on host physiology, both locally and at distant sites. Locally, these bacteria enhance gut immunity and motility as well as reducing intestinal permeability. At distant sites, such as the lungs, they regulate immune defense against viral infection. In the case of the brain, they may influence behavior by decreasing synaptic connectively and increasing anxiety and perception of pain. Moreover, they modulate hepatic metabolism in a manner that decreases energy expenditure and promote adiposity. In addition, absence of gut microbiota leads to more bone mass in association with fewer osteoclasts per surface area of bone.