Serotonin may protect against Gastrointestinal infections: Study

Next, the researchers examined how serotonin affected virulence in living hosts. Using mice, the researchers studied how serotonin might change the ability for Citrobacter rodentium – a mouse gut bacterium often used as an analog for E. coli in humans – to infect and sicken their hosts. These mice were genetically modified to either over- or underproduce serotonin in their gastrointestinal tracts. Those that overproduced this neurotransmitter were less likely to become colonized by C. rodentium after being exposed to this bacterium or had relatively minor courses of illness. Treating mice with fluoxetine (sold under the brand name Prozac) to increase serotonin levels prevented them from getting sick from C. rodentium exposure. However, the mice that underproduced serotonin became much sicker after bacterial exposure, often dying from their illness.

Further experiments identified the receptor for serotonin on the surfaces of both E. coli and C. rodentium, a protein known as CpxA. Because many species of gut bacteria also have CpxA, it's possible that serotonin could have wide-ranging effects on gut bacterial health, Sperandio says.

In the future, she adds, she and her colleagues plan to study the feasibility of manipulating serotonin levels as a way of fighting bacterial infections in the gastrointestinal tract. Currently, few available antibiotics can effectively fight E. coli O157 – some antibiotics actually worsen the consequences of infection, causing the bacteria to release more damaging toxins.

"Treating bacterial infections, especially in the gut, can be very difficult," Sperandio says. "If we could repurpose Prozac or other drugs in the same class, it could give us a new weapon to fight these challenging infections."

Other researchers who contributed to this study include Reed Pifer, Zelia Menezes-Garcia, Santiago Cuesta, and John B. MacMillan, all of UTSW, and Sanjeev Narayanan of Kansas State University.