Human cells in the gut can release molecules that neutralize the toxic effects of Clostridium difficile (C. difficile) infection, a common hospital-acquired infection. The researchers, from David Geffen School of Medicine at UCLA and the University of Texas Medical Branch at Galveston, explained in the journal Nature Medicine that severe C. difficile cases have become more severe recently.

The authors explain that they have identified a molecular process by which the patient’s own body can defend against the effects of CDI (C. difficile infection). This could lead the way to novel treatments for an intestinal disease that is becoming harder to treat.

Millions of Americans are affected by CDI annually, about twice as many today as ten years ago. The scientists say the increased rate is due to a new, highly virulent bacteria strain that has emerged.

The authors say they are preparing for clinical trials using their breakthrough as a new C. difficile infection therapeutic approach. Scientists from the Commonwealth Medical College, Tufts University, and Case Western Reserve University were included in the research.

C. difficile infection is caused by a bacterium, it generally causes diarrhea and can lead to complications, such as colitis (colon inflammation). In very severe cases the patient can die. Patients most commonly acquire CDI while in hospital. Elderly individuals, as well as those on antibiotics for another infection are particularly vulnerable.

One of two powerful antibiotics is currently used to treat CDI. However, up to one-fifth of treated patients relapse within a few weeks.

Co-author Dr. Charalabos Pothoulakis, said:

“We are treating a disease caused by antibiotics with yet another antibiotic, which creates the conditions for re-infection from the same bacteria. Identification of new treatment modalities to treat this infection would be a major advance.”

C. difficile release two powerful toxins into the human gut lumen that bind to intestinal epithelial cells – this triggers an inflammatory response, leading to diarrhea and colitis. The toxins are only released when the bacteria are multiplying.

When patients are administered antibiotics for other infections, bacteria that compete with C. difficile for energy are destroyed, providing C. difficile with a chance to thrive and release its toxins.

The Texan scientists found that when a human has a CDI, the cells in the gut can release molecules that neutralize the toxins. Animal studies showed that when a drug was used to induce the gut to release the molecules (s-nitrosylation), the C. difficile toxins were not able to destroy intestinal cells.

The authors say that forthcoming clinical trials will show whether this also occurs in humans.

Lead author, Tor C. Savidge, wrote:

“Our study suggests a novel therapeutic approach for treating Clostridium difficile infection by exploiting a newly discovered defense mechanism that has evolved in humans to inactivate microbial toxins.”

As well as having potential for CDI treatment, the scientists say their discovery may also have possibilities for treating other types of diarrhea, as well as other (non-diarrheal) diseases caused by bacteria.

Pothoulakis said:

“We already know through gene-sequencing analysis that hundreds of microbial proteins can be regulated by s-nitrosylation. If we are successful with this approach, we may be able to treat other bacterial diseases in a similar way.”

Written by Christian Nordqvist