E. coli O157 and other disease-causing E. coli strains produce a potent toxin called Shiga.
The National Institutes of Allergy and Infectious Diseases estimate that Shiga toxin-producing E. coli causes around 265,000 infections each year in the United States. They also estimate that E. coli O157 causes 36% of these infections.
The World Health Organization (WHO) do not recommend using antibiotics to treat E. coli O157 infections. They indicate that antibiotics might make the infection worse by increasing the risk of complications.
Research at the University of Texas (UT) and Kansas State University in Manhattan, KS, now suggests that drugs that boost serotonin levels, such as the antidepressant Prozac (fluoxetine), could serve as potential treatments.
The scientists found that serotonin ‘reprograms’ E. coli O157 to produce fewer toxins, reducing the severity of the infection.
“Treating bacterial infections, especially in the gut, can be very difficult,” says Vanessa Sperandio, Ph.D., a professor of microbiology and biochemistry at UT Southwestern Medical Center and senior author of the new study. “If we could repurpose Prozac or other drugs in the same class, it could give us a new weapon to fight these challenging infections,” she continues.
The scientists’ published their findings in the journal Cell Host & Microbe.
Scientists know that serotonin works in the brain, where it passes signals between nerve cells and helps regulate sleep and mood, among other functions.
What is less well known is that the gut is home to 95% of all the body’s serotonin, where it controls bowel movement and influences appetite as part of the enteric nervous system.
According to Cell Host and Microbe, studies show that changes in the microbiota influence behavior and have links to neurological diseases, such as autism.
The vast majority of microorganisms in the microbiota are beneficial, ‘friendly’ bacteria that provide health benefits, such as enhancing immunity. Others influence levels of neurotransmitters, including serotonin in the gut.
But scientists know little about how serotonin affects pathogenic gut bacteria.
To find out more, the researchers grew pathogenic E. coli in Petri dishes in a laboratory and exposed them to serotonin. They discovered that the neurotransmitter inhibited the expression of some genes in the bacteria, reducing their ability to cause infections.
Further experiments showed that E. coli exposed to serotonin was less able to damage human cells growing in the laboratory.
The next step was to investigate how serotonin affects the virulence of bacteria in a living host.
To do this, the scientists genetically modified mice to produce too much serotonin in their gut and compared them to mice that they had not genetically modified. They then infected both types of mice with the Citrobacter rodentium (C. rodentium) bacterium, which is the equivalent of E. coli in mice.
The results indicated that bacteria were less likely to colonize mice that over-produced serotonin or caused milder infections. By contrast, mice that scientists did not produce lots of serotonin were more prone to severe infections, and many died.
When the researchers dosed healthy mice with fluoxetine to increase their serotonin levels, it seemed to protect them from C. rodentium infections.
A final round of experiments identified that serotonin binds to a protein receptor called CpxA in both E. coli and C. rodentium.
When serotonin binds to CpxA, it acts as a switch, turning off the expression of virulence genes in the bacteria.
In their paper, the researchers note that many species of gut bacteria, including the pathogens Salmonella, Yersinia enterocolytica,and Shigella disenteria, also have CpxA receptors. So serotonin may help tame them as well.
Sperandio and her colleagues plan to investigate how doctors could potentially use other drugs that alter serotonin levels as new treatments for gut bacterial infections.
The researchers’ work adds to evidence that bacteria play a pivotal role in the gut-brain axis — the two-way communication between the brain and digestive system — and the way it influences our physical and mental health.
CpxA is also the receptor for a molecule called indole that bacteria use to send messages to each other.
Indole and serotonin are structurally similar. Some research suggests that indole produced by gut bacteria can accumulate in the brain, affecting mood and behavior. In their paper, the authors write:
“Importantly, the fact that bacteria have receptors to neurotransmitters opens a broad array of possibilities on how the gut-brain axis functions as a two-way street between microbes and their mammalian hosts.”
