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Fecal transplants alter protein composition of the gut

Joshua Elias
Sep 28 2016

Transferring stool from a healthy mouse to a sick mouse that suffers from gastrointestinal infections promotes a quick return of health by restoring its gut to a more normal state, Stanford research shows

By H. Winnie Liang

Scientists at Stanford University have found that proteins in an animal’s stool might be a simple, highly sensitive way to track bacterial infection and subsequent recovery in the gut. If the technique works in humans, it could become a quick way of knowing what is making a person sick and of providing appropriate treatments.

Imagine a disease infection as an arms race between the microbes and the host, where the host secretes proteins whose function is to hold the microbes at bay.  In response, the microbes produce proteins that can digest the host’s proteins.  To counterattack, the host then secretes other proteins that disrupt and degrade those of the microbe.

Those arms – or proteins – end up in the hosts’ feces and can tell scientists a lot about the turf war raging within, according to research published in Cell Reports led by Joshua Elias, a professor of chemical & systems biology, and Justin Sonnenburg, a professor of microbiology and immunology. Both Elias and Sonnenburg are also members of Stanford ChEM-H.

One rationale behind Elias’ work comes from the anecdotes of human patients infected with Clostridium difficile, an intestinal bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon. Infected individuals could become severely ill, and often did not respond to antibiotics. When these patients received a fecal transplant from healthy donors, they felt better in mere hours.

Given the complexities and information richness of the proteins produced by both bacteria and the host, Elias reasoned that monitoring the relative abundance of these proteins in the stool might provide clues as to what’s happening within.

In their recent work, Elias and his team examined the protein profiles in the feces of healthy mice, mice treated with antibiotics, and then infected with C. difficile.  They noticed that the antibiotic-treated mice alter the types of proteins their bodies produce and are thus more susceptible to subsequent C. difficile infection.  However, upon receiving a single dose of stool from other healthy mice, the infected mice began to secrete proteins similar to those in healthy mice in their feces. These results suggest that the transplanted stool contains something that silences the internal battle and restores the gut to its normal state. 

These findings raised the question of what was being transferred in these fecal transplants. Beneficial microbes?  Useful host proteins?  Small molecules?  Bacteria-infecting viruses?  Elias said, “All these things are exciting possibilities that we want to study further.” 

This study could have important implications for the healthcare industry.  Imagine one day, with a set of few proteins in stool, we can quickly identify the disease and the disease state of patients, or even detect an outbreak of viruses or other disease-causing microbes or bacteria before they even start to spread through urban centers.  The use of fecal transplant to re-establish equilibrium in our bodies during an infection raises the possibility of full recovery without the complication of antibiotic resistance.

 

“There are surprises all the time, when you are working with so much rich data,” Elias says. “The excitement underlies just what this field has the potential to do.”

H. Winnie Liang is a 7th year chemistry PhD student in the lab of Kelly Gaffney