Aug. 17, 2020

Researchers find a peptide that 'wakes up' the gut against harmful bacteria

This paradigm shift in understanding may lead to an alternative to antibiotics
Dr. Ravi Holani, PhD
Dr. Ravi Holani, PhD

Researchers in the Faculty of Veterinary Medicine (UCVM) and the Cumming School of Medicine (CSM) have discovered that cathelicidin, a small peptide that’s produced naturally in the gut of humans and animals, is able to detect harmful bacteria in the colon and co-ordinate the immune system to mount an attack against the pathogen.

The scholars have published their study in Gut Microbes, a leading scientific journal.

“The gut is interesting because it needs to live in peace with bacteria all the time without reacting, However, when you have an infectious bacteria like Salmonella the gut needs to react.” says Dr. Eduardo Cobo, DVM, PhD, an associate professor of cattle health at UCVM and the senior author of the paper.

The gut has to distinguish between good bacteria and bad bacteria.

Cobo’s former doctoral student, Dr. Ravi Holani, PhD (pictured above), found that when harmful bacteria such as Salmonella are present in the gut, cathelicidins bind with the bacteria or parts of it. This process “wakes up the gut” and stimulates the gut wall to send a signal to attract specific white blood cells to the colon to attack and kill the harmful bacteria.

“This is a paradigm shift in in our understanding of how the body’s own antibacterial compounds work to protect us from infection-caused inflammation,” says co-author of the study Dr. Morley Hollenberg, MD, PhD, a professor of physiology and pharmacology in CSM, and a member of the CSM’s Snyder Institute for Chronic Diseases.

Study authors Eduardo Cobo, left, and Morley Hollenberg.

Many researchers have already looked at how cells can excrete cathelicidins to ward off bacteria. But this research found that the peptides have “a newly discovered role inside the body,” says Hollenberg.

“The body has figured out a way to use these compounds in a very different way, almost like small hormones. When produced by the body’s intestinal cells, they allow the tissue to bind pieces of the harmful bacteria. This process stimulates the gut to send a message to our white blood cells to attack the bacteria.”

New knowledge helpful for health of both humans and animals

This new knowledge about cathelicidins will help researchers promote health and well-being in humans and animals, as well provide new opportunities to control infections and has long-term potential to help create an alternative to antibiotics.

“We now understand how this locally produced hormone can help fight off inflammation in the gut,” says Hollenberg. “It's not going to result directly in a drug, but it unmasks a new therapeutic target for dealing with gut inflammation.”

As antibiotic resistance in humans and animals grows at alarming rates, researchers the world over are racing to create new antibiotics to fight superbugs and other devastating infections. But this research presents another approach: training the host itself to fight harmful bacteria.

“We have a very effective immune system. This paper helps us understand how we are so effective, pick up those targets and then explore those alternative therapies,” says Cobo. “By exploring this mechanism we can train the body to fight bacteria. By using cathelicidin, we can say to the gut ‘OK, this is dangerous, you need to react.’ That’s an active way to fight bacteria versus the normal conventional antibiotics where we are more passive as a host. We can train our immune system to react.”