- The fungi that reside in the human gut are generally safe to healthy people, but they have the potential to be pathogenic and can exacerbate Crohn’s disease in some people.
- According to the findings of a recent study, the immune system exclusively targets an invasive version of the fungus Candida albicans, giving the innocuous form a competitive edge.
- As a result of this immunological interaction, a more harmonic and mutually advantageous relationship between the fungus and its host is established.
- In theory, a C. albicans vaccine that is already available could be used to fine-tune the relationship in people who have irritable bowel disease (IBD), thereby reducing the characteristic gut inflammation that is associated with the disease.
The human gut is home to an exceptionally varied ecosystem of bacteria, viruses, archaea, and fungi, all of which contribute to the health of the individual.
Typically, these microbes coexist peacefully with their human hosts, forming intricate, mutually beneficial interactions with them.
By contrast, health disorders that involve inflammation of the gut can cause these relationships to be disrupted and weakened. For example, evidence reveals that certain fungal species that are normally considered harmless can aggravate IBD in healthy persons.
Crohn’s disease and ulcerative colitis are the two most common kinds of inflammatory bowel disease (IBD). Intermittent symptoms, such as diarrhoea and abdominal pain, characterise these chronic illnesses that are difficult to treat.
People who suffer from inflammatory bowel disease (IBD) are known to have elevated levels of a group of fungi known as Candida in their gut, particularly the species C. albicans.
Now, according to a new study, it has been revealed how the immune system of someone who has a healthy gut may maintain a peaceful relationship with potentially hazardous fungus such as Candida albicans.
Immunoglobulins, as identified by the researchers, target structures known as hyphae, which are long, fine filaments that fungus employ to penetrate the tissues of their host.
Antibodies directed against hyphae were found to restrict the growth of the organism’s invasive, “pathogenic” form in mice while encouraging the formation of a benign, spherical form.
Kyla Ost, Ph.D., a postdoctoral researcher at the University of Washington who led the work, said, “The immune system is restricting Candida to its least harmful form.”
This demonstrates that communication between host and microbe can be friendly, rather than adversarial, in order to benefit both parties, according to her.
A vaccine that induces the immune system to make more of these specific antibodies may be effective in reducing inflammation in persons with inflammatory bowel disease (IBD).
The findings of the study have been reported in Nature.
Adhesive proteins
Immunoglobulins against four common species of intestinal fungi were examined in faecal samples from healthy individuals and people suffering from IBD.
They discovered that one species, Candida albicans, elicited a very robust antibody response in both subjects with and without inflammatory bowel disease.
In experiments with mice, the researchers discovered that some of these antibodies were directed against adhesins, which are proteins that allow fungal hyphae to adhere to the mucosal wall of the gut and penetrate it.
Further trials revealed that the antibodies provided a competitive advantage to the rounder, benign form of Candida albicans over the invasive form of the organism.
According to the findings of the research, the hyphal form of Candida albicans increased damage to the intestine, whereas the spherical form of the yeast actually reduced inflammation.
Together, the findings suggest that normal antibody responses in the gut prevent IBD by targeting invasive C. albicans, which, in turn, provides a competitive advantage to the benign form of the organism.
The scientists also demonstrated that a previously developed vaccine, which elicits an immune response against the adhesins of fungal hyphae, can minimise damage to the gut in a model of inflammatory bowel disease.
The vaccine, which has been tested in a clinical trial for the prevention of vaginal yeast infections, was found to protect the guts of mice against harm caused by the invasive form of Candida albicans (Candida albicans).
“Our ultimate goal is to test this vaccination method in humans as a means of treating or preventing IBD,” Dr. Ost stated in an interview with Medical News Today.
She continued, “However, we still have a lot of work to do to better understand how this vaccine works in animal models before we can move on with clinical trials.”
A mutually beneficial relationship
Dr. Ost emphasised that the interaction between Candida albicans and its human hosts has the potential to be beneficial to both parties in his presentation.
“We discovered that the majority of the advantages come from the elimination of the invasive form of this fungus. Recently published research suggests that these fungus may actually assist our bodies in fighting infection by activating protective immune responses,” she explained.
A statement from Gerard Honig, Ph.D., the director of research innovation at the Crohn’s & Colitis Foundation, which assisted in funding the new research, expressed his delight with the results:
“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 stated that there are multiple lines of evidence indicating fungus play a major role in inflammatory bowel disease (IBD), particularly Crohn’s disease.
His colleagues pointed out that blood tests for antibodies against microorganisms, including fungi, have been used for years to aid in the diagnosis of Crohn’s disease and to determine the prognosis of individuals with the disease.
In his words: “However, the functional importance of antifungal immune responses in inflammatory bowel disease (IBD) has remained unclear, and this question is elegantly addressed in our current work.”
Dr. Honig noted that additional research would be required to confirm and extend the findings before clinical trials of potential new medicines could be conducted in humans.
