Calcium Could Usher In Next Breakthrough in C. difficile Treatment

Treatment regimens that account for dietary calcium intake may help decrease the risk of Clostridium difficile (C. difficile) infections in specific patients, according to a new report.

Researchers from the University of Michigan Medicine found that calcium is required for C. difficile spore germination, and that adding or depriving spores of calcium affects their ability to germinate.

When C. difficile spores reach the gut, they pass through the gut’s acidic environment unharmed, researchers noted. Much of the spore’s weight comes from calcium — which helps trigger its germination.

Michigan Medicine research from the 1980s showed that bile salts can trigger enzyme activation leading to germination, and further developments showed that the amino acid glycine was a vital component to this process.

In their investigation, researchers depleted calcium from harvested mouse ileal contents, said first author Travis Kochan (pictured), a PhD student. The team found that these mouse models had a 90 percent lower rate of C. difficile wild-type spore germination, and that mutant spores did not germinate at all. When they added calcium back to the ileal contents, germination of wild and mutant spore types was restored.

“These spores don’t want to germinate in the wrong place,” Kochan said. “C. difficile spores have specialized to germinate in the gut environment, especially in the environment of the small intestine, where calcium and the bile salt injection from the liver comes in.”

A concurrent US Food and Drug Administration (FDA) investigation from the Center for Biologics Evaluation and Research lab found that calcium, not glycine, was critical for the germination process.

According to researchers, one way to combat infection may be to add more calcium to patients’ diets. If all the spores germinate at once due to increased calcium levels, the study authors theorized, then antibiotics designed to kill only the germinated spores could be introduced.

This may subsequently stop the transmission of spores throughout hospitals through diarrhea.

Vitamin D is well-known to facilitate calcium absorption in the gut, Kochan said, which may boost resistance to C. difficile. The researchers are next planning to test the role of Vitamin D in preventing infection and to determine if increased dietary calcium would create an infection in a normally unsusceptible environment.

The researchers noted that patients with Vitamin D deficiencies can be up to 5 times more likely to get C. difficile infections. If these patients were to take Vitamin D supplements, they would have increased levels of free calcium in their gastrointestinal tracts, Kochan said.

Additionally, Kochan said he is working on characterizing the specific mechanisms behind calcium induced germination, including which proteins calcium interacts to generate this process.

The study, “Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores,” was published online in the journal PLOS ONE.

A press release regarding the study was made available.

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