The guts of C. elegans, highlighted by fluorescent proteins produced when the nervous system is targeted by drugs.
Image credit: Alejandro Aballay Lab, Duke University
The gut and brain are connected by a dense network of neurons.
These connections are responsible, unsurprisingly, for signaling hunger and satiety.
More surprisingly, gut-brain connections also play a role in signaling love, fear, safety, and danger.
As with other networks, they utilize a cocktail of neurotransmitters; one of the chemicals commonly used is dopamine, known for its role in reward and addiction.
It is only now that the complexity and ramifications of these relationships are coming to light.
Antipsychotics and the gut
A study, published this week in Current Biology, investigated whether drugs designed to manipulate dopamine signaling, such as antipsychotics, could have an effect on inflammation. In other words, could drugs that work on the nervous system affect the immune system, two biological systems that, until recently, were considered to be separate entities.
The research group was headed up by Alejandro Aballay, Ph.D., a professor of molecular genetics and microbiology at Duke School of Medicine in Durham, NC. He believes that the nematode worm Caenorhabditis elegans is a useful model to study the gut-brain interaction.
C. elegans' nervous system contains just 302 neurons, compared with a fruit fly's 250,000 or a human brain's 100 billion; they also have a very basic immune system.
Aballay and his team first noted a gut-brain-immune interaction in C. elegans during a study they carried out in 2009. The team bombarded the nematodes with a range of chemicals in the search for compounds that would help protect the creatures from bacterial infection.
Of more than 1,000 drugs, 45 were found to switch on the immune pathway. Half of these drugs worked on the nervous system, and a few of them blocked dopamine activity. This finding provided the basis for the current study.
Dopamine influencing immunity
For this next phase, the team set out to investigate the effects of dopamine and dopamine signaling pathways on the nematodes and their immune system.
They blocked dopamine's effects using a drug normally used for manic depression and schizophrenia, called chlorpromazine. When C. elegans was introduced to a common bacterium - Pseudomonas aeruginosa - it was more resilient to attack.
Conversely, when the team applied dopamine to the worms, they became more susceptible to infection.
As theorized, the researchers showed that by manipulating dopamine levels in the C. elegans, they could control inflammation in the gut.
The team believes that dopamine signaling controls the body's inflammatory response so that it is prevented from running amok - as it does in certain autoimmune conditions, where the immune system turns its weapons on healthy cells.
"Worms have evolved mechanisms to deal with colonizing bacteria. That is true for us as well. Humans have trillions of microorganisms in our guts, and we have to be careful when activating antimicrobial defenses so that we mainly target potentially harmful microbes, without damaging our good bacteria - or even our own cells - in the process."
Prof. Alejandro Aballay, Ph.D.
Prof. Aballay continues: "We are talking about an existing set of drugs and drug targets that could open up the spectrum of potential therapeutic applications by targeting pathways that fine-tune the inflammatory response."
Although the jump from nematode to human is a sizable one, Prof. Aballay hopes that targeting the nervous system to influence the immune system could "potentially be used to treat conditions such as rheumatoid arthritis, autoimmune disease, cancer, inflammatory bowel disease, and Crohn's disease" in the future.
Prof. Aballay plans to continue his research into the fine-tuning of the immune system. As we learn more about the gut-brain-immune interaction, our view of the ways in which our bodies are influenced looks set to be substantially changed.