About this Research Topic
It has been realized that infections of various viruses, especially
Herpesviridae and HIV, are associated with different neurodegenerative diseases. Viruses can be causative agents or at least co-factors via inducing alterations and degenerations of neurons, both directly and indirectly. Increasing evidence suggests that gut microbiota's diversity and balance play a critical role in infectious diseases and neurodegeneration. Gut microbiota and their metabolites interact with the host through biochemical, immunological, and physiological processes to affect virus infection and neurodegeneration.
Communications between the central nervous system and the gut axis relied mainly on direct neural communication, endocrine pathways, and immune regulation, further confirmed by fecal microbiota transplantation and probiotic intervention. Exogenous bacterial metabolites can also directly promote viral infection, impair neuronal function, and induce neuroinflammation, promoting neurodegeneration. Therefore, elucidating the role and connection between gut microbiota and virus infection will facilitate the development of novel therapeutic strategies against neurological diseases.
To adapt to the changes of the external environment induced by the
day/night cycle, physiological activities of most creatures exhibit
diurnal alterations within a 24-hour rhythm, the so-called biological
rhythm (circadian clock), which is controlled by the transcription-translate feedback loops mediated by several key transcriptional regulators (e.g., Clock, Bmal1, Per, Rev-erb, RORs). Importantly, the composition and function of gut microbiota are influenced by host circadian rhythms via intrinsic circadian clocks and exhibit oscillatory behavior in response to a fluctuating environment (e.g., light, diet, host behavior, pathogenic microbe infection), which in turn, regulate host circadian pathways. For instance, microbiota-derived metabolites, such as short-chain fatty acids and bile acids, can alter circadian rhythms. Accordingly, the dysregulated interaction between the host circadian clock and microbiota oscillations influence many physiological processes, including host metabolism, endocrine system regulation, and immune system function. Alterations of circadian rhythms due to shift work or jet lag have all been associated with altered microbiota composition and several metabolic/inflammatory-related diseases, and an increased neuro-disorders. Furthermore, circadian clocks modulate host anti-viral immunity to impact viral infection, whereas viruses modulate molecular circadian clocks to facilitate their replication and infection.
Understanding how the circadian clock-gut microbiota axis affects
viral infection and neurodegeneration will promote circadian
modulating therapies involving both pharmacotherapy and chronotherapy. Moreover, it will reveal the disease's rhythm characteristics and build a more accurate host-microbiome mutual model. However, studies have mostly examined the effect of either circadian clock or gut microbes independently, but not together. More work needs to be done to examine how both the microbiota-gut-brain axis and circadian clock influence neurodegenerative diseases and how they interplay with one another in the context of diseases.
In this Research Topic, we encourage contributions as Original Research and Review articles covering interesting new findings on the crosstalk of circadian clocks, gut microbiota, and viral infection-associated neurodegeneration. We particularly encourage research that includes:
• The molecular interplay between the circadian clock and virus infection.
• The influence of gut microbiota and their metabolites on the virus
infection and neurodegenerative diseases.
• The function of the circadian clock in gut microbiota and viral
• The influence of probiotics and bioactive compounds on circadian
clock-gut microbiota axis and virus infection.
• Comparative microbiome analysis in different conditions and its
relevance for neurodegeneration.
• Using sequencing and bio-informational methods to identify
health-promoting functional microorganisms, analyze metabolites that control key processes and investigate their potentials in the diagnosis and therapy.
Keywords: gut microbiota, circadian clock, neurodegeneration, virus infection
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