Understanding how gut viruses affect the brain

Medical News: Scientists are continuing to uncover new connections between the gut and the brain, revealing fascinating details about how viruses in the digestive system can impact the nervous system. Recent research has shown that certain viruses, particularly enteric viruses, can travel from the gut to the brain, causing serious conditions such as meningitis, encephalitis, and even acute paralysis. This Medical News report explores the intricate relationship between the gut and brain, focusing on how some of these viruses spread and the severe health complications they can trigger. The research, conducted by scientists from the University of Cambridge-UK and Amsterdam UMC-Netherlands, highlights key mechanisms of viral infection, bringing attention to how viruses manage to cross over into the brain from the gut.


Possible routes of gut-to-brain virus infections. Following primary infection in the intestinal tract, viruses can use the circulatory route (vascular and lymphatic systems) or the enteric nervous system (neuronal route) to reach the CNS. Along the way, the viruses must overcome several barriers before entry and infection of the cells in the CNS.

What Are Enteric Viruses?
Enteric viruses are a group of viruses that primarily affect the gastrointestinal system, often causing gastroenteritis, an inflammation of the stomach and intestines. While most enteric infections are confined to the gut and handled by the body's immune system, certain viruses have the ability to bypass this defense. In rare cases, these viruses can travel beyond the gut, reaching areas like the nervous system. This article examines how these infections become neuroinvasive, focusing on specific viruses that transition from gut to brain.
 
Types of Neurotropic Enteric Viruses
Neurotropic enteric viruses are those capable of infecting nervous system cells. The most well-known among them are from the Picornaviridae family, including enteroviruses and astroviruses. These viruses often start their infection in the gut but can spread to the central or peripheral nervous systems, particularly in vulnerable populations like infants and immunocompromised individuals. The study outlines three main types of neurotropic viruses:
 
-Enteroviruses - Responsible for a wide range of conditions, including hand, foot, and mouth disease (HFMD) and acute flaccid paralysis. Enteroviruses like EV-A71 and coxsackieviruses have been linked to outbreaks of neurological illnesses worldwide.

-Parechoviruses - A lesser-known but significant cause of neurological disease, particularly in young children. HPeV-3, a specific genotype, is noted for causing severe CNS complications.
 
-Astroviruses - Often associated with gastroenteritis, but in some cases, these viruses have been linked to CNS infections in children, the elderly, and those with weakened immune systems.
 
How Do These Viruses Reach the Brain?
The gut-brain axis refers to the complex, two-way communication syste m between the digestive system and the brain. While this connection is primarily studied for its role in regulating metabolism and immune response, viruses can also exploit it to spread from the gut to the nervous system. There are two primary routes through which viruses can travel from the gut to the brain:
 
-Axonal Transport: The enteric nervous system (ENS) connects the gut to the brain via nerves like the vagus nerve. Some viruses use this neural pathway, traveling along the nerve fibers to reach the central nervous system.
 
-Fluidic Systems: The lymphatic and blood systems offer another route. Once viruses breach the intestinal barriers, they can enter the bloodstream and spread to the brain through the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB). Both barriers are designed to protect the brain, but certain viruses can find ways to bypass or weaken these defenses.
 
Key Findings of the Study
The researchers found that several factors help viruses spread from the gut to the brain. One crucial factor is the virus’s ability to survive the harsh conditions of the digestive system and adapt to different environments as it moves through the body. Certain viruses, such as enteroviruses and astroviruses, have mechanisms that allow them to remain stable in the acidic stomach and continue infecting other parts of the body.
 
Moreover, the study highlights how viruses can take advantage of immune-compromised individuals, where immune responses might be too weak to prevent the virus from spreading. Children, in particular, are at risk, as their immune systems are still developing.
 
One of the major revelations of the study is that viral spread is not entirely random. Instead, viruses seem to undergo a selection process in the gut, where only the strongest variants with the ability to infect the nervous system survive and spread. The study provides valuable insights into how these viruses evolve and adapt, making them even more dangerous once they enter the brain.
 
How the Gut May Help Select Dangerous Virus Strains
The gut, with its vast surface area and dense network of microorganisms, serves as a large and complex environment where viruses can mutate and adapt. This offers an ideal location for viruses to evolve, increasing the chances of developing strains that can infect the brain. The study found that certain viral mutations associated with neurovirulence - the ability to infect the brain - may be selected within the gut environment.
 
The role of gut bacteria in supporting viral infections is also a key finding. Some bacteria can enhance the survival of viruses, allowing them to spread more efficiently. For instance, the study found that bacteria in the gut can bind to certain viruses, stabilizing them and making it easier for these viruses to survive and infect other parts of the body.
 
Conclusions
The research presented sheds light on the complex ways in which enteric viruses transition from the gut to the nervous system. Understanding these processes is essential in developing treatments and vaccines for neurotropic viruses. This knowledge may help prevent serious conditions such as encephalitis, meningitis, and acute flaccid paralysis.
 
The key conclusions from the study are:
-Adaptation and Selection in the Gut: The gut acts as a breeding ground for viruses, where only the strongest variants, capable of infecting the brain, survive.

-Importance of the Immune System: Individuals with weakened immune systems, such as young children and immunocompromised patients, are at a higher risk of having these viruses spread from the gut to the brain.
 
-Virus Spread Mechanisms: Axonal transport and fluidic systems are the primary pathways used by viruses to move from the gut to the brain.
 
-Potential for New Treatments: By understanding the molecular mechanisms that allow these viruses to become neurotropic, researchers may develop targeted antiviral therapies or vaccines to prevent these infections from becoming severe.
 
The study findings were published in the peer-reviewed journal:  Cellular and Molecular Life Sciences.
https://link.springer.com/article/10.1007/s00018-024-05450-6
 
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