Gut calcium tied to C. difficile germination in mice

Last Updated: 2017-07-20

By David Douglas

NEW YORK (Reuters Health) - Excess calcium in the gut appears to be a key ingredient in metabolic activation of Clostridium difficile, according to mouse studies.

As Dr. Philip C. Hanna told Reuters Health by email, "linking calcium to germination of C. difficile spores may, potentially, answer old mysteries and open leads for developing new countermeasures."

"One old mystery," he added, "is why patients taking certain medications, or have Vitamin D issues, are at higher risk for contracting C. difficile infections (CDIs). We believe the higher calcium makes for more robust spore germination. "

In a paper online July 13 in PLOS Pathogens, Dr. Hanna of the University of Michigan Medical School in Ann Arbor and colleagues note that CDI typically occurs after ingestion of infectious spores by a patient who has been treated with broad-spectrum antibiotics. Spores germinate when they encounter bile salts, glycine and other agents in the small intestine.

Bile salts are known to be essential but to directly test if intestinal calcium plays an important role in such germination, the team collected ileal contents from antibiotic-treated, noninfected mice, calcium was depleted, and ex vivo germination assays were performed.

In those that contained about 15 nM of calcium, all spores from two strains germinated within an hour. However, calcium depletion completely prevented germination of one strain and allowed only a 10% success rate in the other.

In a statement, Dr. Hanna said, "These spores are like armored seeds, and they can pass through the gut's acidic environment intact. Much of the spore's own weight is made of calcium, but we've shown that calcium from the gut can work with bile salts to trigger the enzyme needed to activate the spore and start the germination process."

These and other findings, Dr. Hanna went on to tell Reuters Health, suggest the "benefits of reducing extra/unneeded calcium in the GI systems, of those patients already recognized (to be) at high risk for CDIs, is an attractive area for near-term investigation. We will start using animal models first, but it's easy to envision that line of inquiry translating to people."

To deal with recurrence, which may be caused by germination of dormant spores, he added, "It may well be that increasing/supplementing dietary calcium, at the same time as providing the antibiotics, may be a 'counter' to those dormant spores and allow a stronger chance for full clearance by the antibiotics."

"Again," Dr. Hanna concluded, "we will be methodical and careful and test these theories in mice before considering making any recommendations about how we might better treat people."

SOURCE: http://bit.ly/2tK1u4x

PLoS Pathog 2017.