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An antifungal might help redress the microbial imbalance associated with IBD. SubstanceP/Getty Images
  • The fungi that live in the human gut are harmless for most healthy people, but they are potentially pathogenic and can exacerbate Crohn’s disease.
  • A new study has found that the immune system only targets an invasive form of the fungus Candida albicans, which gives the harmless form a competitive advantage.
  • This immune interaction promotes a more harmonious, mutually beneficial relationship between the fungus and its host.
  • An existing vaccine against C. albicans could, in theory, be used to fine-tune the relationship in people with inflammatory bowel disease (IBD), helping reduce the characteristic gut inflammation.

The human gut is home to an extraordinarily diverse community of bacteria, viruses, archaea, and fungi.

Usually, these microorganisms live harmoniously with their human hosts in complex, mutually beneficial relationships.

These alliances are disrupted by health conditions that involve inflammation of the gut, however. For example, research suggests that certain fungal species that are harmless in healthy individuals can exacerbate IBD.

There are two major types of IBD, Crohn’s disease and ulcerative colitis. These are chronic conditions characterized by intermittent symptoms, such as diarrhea and abdominal pain.

People with IBD are known to have increased amounts of a group of fungi called Candida in their gut, particularly the species C. albicans.

A new study has now shed light on how the immune system of a person with a healthy gut maintains a harmonious relationship with potentially harmful fungi, such as C. albicans.

The researchers discovered that antibodies target structures called hyphae, which are the long, fine filaments that fungi use to invade the tissues of their host.

In mice, antibodies targeted at hyphae suppressed the invasive, “pathogenic” form of the organism and encouraged the growth of a benign, rounded form.

“The immune system is constraining Candida to its least pathogenic form,” says postdoctoral researcher Kyla Ost, Ph.D., who led the investigation.

“This is showing us that the communication between host and microbe can be friendly, as opposed to antagonistic, in order to benefit both,” she explains.

A vaccine that encourages the immune system to produce more of these particular antibodies could help reduce inflammation in people with IBD.

The research has been published in Nature.

The scientists looked for antibodies to four common species of gut fungi in fecal samples from healthy individuals and people with IBD.

They discovered that the antibody response to one species, C. albicans, was particularly strong, both in participants with and without IBD.

In tests in mice, the team found that some of these antibodies targeted proteins called adhesins that allow fungal hyphae to stick to the mucosal wall of the gut and invade it.

Further experiments showed that the antibodies gave the rounded, benign form of C. albicans a competitive advantage over the invasive from.

In a mouse model of IBD, the scientists found that the hyphal form of C. albicans exacerbated damage to the intestine, whereas the rounded form actually reduced inflammation.

Together, the results suggest that normal antibody responses in the gut inhibit IBD by targeting invasive C. albicans, which, in turn, gives the benign form a competitive edge.

Finally, the scientists showed that an existing vaccine, which provokes an immune response to the adhesins of fungal hyphae, could reduce damage to the gut in a model of IBD.

The vaccine, which has undergone a clinical trial for preventing vaginal yeast infections, protected the guts of mice from damage associated with the invasive form of C. albicans.

“Our ultimate goal is to test this vaccination strategy as a way to treat or prevent IBD in people,” Dr. Ost told Medical News Today.

“However, we still have a lot of work to better understand how this vaccine works in animal models before we pursue clinical trials,” she added.

Dr. Ost highlighted that the relationship between C. albicans and its human hosts was potentially beneficial for both parties.

“We found that the benefits are mostly from the clearance of the invasive form of this fungus. However, recent studies suggest that these fungi may help our body fight off infection by promoting protective immune responses,” she said.

Gerard Honig, Ph.D., the director of research innovation at the Crohn’s & Colitis Foundation, which helped fund the new research, welcomed the findings:

“Although treatments for IBD are available, they have major limitations. There is a critical need for therapeutic strategies that directly target and modulate the dysregulated interactions between the microbiome and the immune system that cause these diseases.”

Dr. Honig said that several lines of evidence suggest that fungi play an important role in IBD, particularly Crohn’s disease.

He pointed out that blood tests for antibodies against microbes, including fungi, have been used for years to help in the diagnosis of Crohn’s and to determine patients’ prognosis.

“However, the functional significance of antifungal immune responses in IBD has been unclear, and this question is elegantly addressed in this new work,” he said.

Dr. Honig emphasized that more work would be needed to confirm and extend the findings before proceeding to clinical trials of potential new treatments.