Phage Interactions with the Nervous System in Health and Disease

Abstract

The central nervous system manages all of our activities (e.g., direct thinking and decision-making processes). It receives information from the environment and responds to environmental stimuli. Bacterial viruses (bacteriophages, phages) are the most numerous structures occurring in the biosphere and are also found in the human organism. Therefore, understanding how phages may influence this system is of great importance and is the purpose of this review. We have focused on the effect of natural bacteriophages in the central nervous system, linking them to those present in the gut microbiota, creating the gut-brain axis network, as well as their interdependence. Importantly, based on the current knowledge in the field of phage application (e.g., intranasal) in the treatment of bacterial diseases associated with the brain and nervous system, bacteriophages may have significant therapeutic potential. Moreover, it was indicated that bacteriophages may influence cognitive processing. In addition, phages (via phage display technology) appear promising as a targeted therapeutic tool in the treatment of, among other things, brain cancers. The information collected and reviewed in this work indicates that phages and their impact on the nervous system is a fascinating and, so far, underexplored field. Therefore, the aim of this review is not only to summarize currently available information on the association of phages with the nervous system, but also to stimulate future studies that could pave the way for novel therapeutic approaches potentially useful in treating bacterial and non-bacterial neural diseases.

Keywords: antibiotic resistance; blood–brain barrier; central nervous system; cerebrospinal fluid; cognitive processing; gut phageome; gut–brain axis; intranasal delivery; phage display; phage therapy; therapeutic phages.

Figure 1

Possible phages interactions with CNS.

Figure 2

Possible routes of entering the CNS by bacteriophages. (A) Intranasal administration; (a) transcellular pathway; (b) intracellular pathway. (B) Entering from circulation through the BBB by either transcellular pathway or by the Trojan horse mechanism.