Q&A: Yeast common in cheese, processed meats impairs healing in Crohn’s
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Researchers from Cleveland Clinic found an infection that prevents healing in patients with Crohn’s disease, according to study results published in Science.
Healio Gastroenterology spoke with Thaddeus Stappenbeck, MD, PhD, chair inflammation and immunity at Cleveland Clinic, about results from the study that examined the yeast, Debaryomyces hansenii. Investigators found higher levels of the yeast among patients with Crohn’s disease. The results showed D. hansenii was abundant in inflamed regions of the colon and small intestine, which may be a sign of unhealed intestinal wounds.
Healio: What were the key results and conclusion from the study?
Stappenbeck: Microbial drivers have been proposed many times for inflammatory bowel disease. There’s been a lot of interesting studies with the specific types of bacteria, viral infection and even yeast. What differentiates our study is that we found that a specific and dominant yeast species was present within the non-healing areas of the intestine. Many previous studies were surveys of what’s present in the intestinal lumen,based on sequencing studies. Investigators found enriched microbes in IBD that could stimulate inflammation . Our study used a combination of human and mouse studies that looked at non-healed ulcers. We found that the fungal microbe wasn’t just driving an inappropriate immune response but was actually preventing repair.
Healio: What were the key takeaways of the study that can be applied to patient care?
Stappenbeck: We used mouse studies to test the hypothesis that this fungal inhibits repair and based on these results we propose that this same microbe can inhibit repair in patients with IBD. Now, our goal is to understand how to identify IBD patients who actually have this particular infection in areas of non-healed wounds. Obviously, we can do an endoscopy and a biopsy and then try to grow the microbe . This is laborious, so we’d like to have a blood test to be able to definitively say who has this infection and who doesn’t. Then, for patients who have the infection, we’d like to have a way to actually treat them. There are several broad-spectrum antifungals that exist. These are drugs that can’t be used lightly with patients because they can potentially have serious side effects. However, if you know there’s an infection and you have good evidence for this, then there’s impetus for trying to use these antifungals in select patients. The key is going to be which antifungal will target this fungal microbe the best, and then for the future, can we develop better antifungals that will specifically target this organism in these patients?
Healio: Will there be future research regarding this study?
Stappenbeck: I call this a door-opener project, as this is an initial discovery. Now on the clinical side, there’s a lot of work that has to be done. We’ve looked in primarily Caucasian cohorts at two medical centers in Saint Louis and in Los Angeles, but now we would like to look at other cohorts of patients with IBD around the world and in different groups. One group we haven’t looked at is pediatric patients, so that’s something we’re very interested in. We would like to look at various ethnic groups within the United States that we haven’t looked at including African Americans. It would be very interesting to look at this in different countries and see if this is the case as well. I have colleagues around the world who I hope will gear up and also take a look at this question in their patients.
There’s also a simple question of why does this fungal organism get into the wounds in the first place and why does it stay there? We’re very interested in how that happens. There have been a lot of studies that showed there are a lot of different fungal organisms present in the lumen of the intestine, but this one particular species seems to be the one type of microbe that can get into wounds. We’re very interested in how that happens. And why this one essentially wins out over all the other ones. We have some leads on how it inhibits repair, but we’d like a lot more detailed mechanism on that.
I’ve appreciated the discussions that have happened on Twitter over the last few days. D. hansenii is a microbe that is present in a lot of food, so industrial food companies use this quite a bit. It’s used in making cheeses, processed meats and its present in some wine. It has properties that make it particularly useful in the production of food. We don’t know if strains that are used in food production actually are the ones that inhabit the ulcers in patients with Crohn’s disease, so that’s something that we’re going to have to take a very careful look at. We have patient strains that have been described in the paper, ones that we’ve isolated from patients. We’re isolating strains from foods and we’re going to compare the two and see if the food isolated strains actually behave the same way. There are very likely many strains even within the species of yeast. It’s really interesting because people are wondering, if they have Crohn’s disease, should they be eating cheese. This is going to be not an academic point, it’s actually very practical.
Perspective
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Florian Rieder , MD
This is an interesting study showing that Debaromyces hansenii present in the CD intestine had a direct effect on intestinal repair. These findings represent a major advance in the field. Alterations in the intestinal mycobiome in CD compared with healthy individuals have been known, but this work links a selective organism to a function in relation to intestinal wound healing. This was shown in a thorough set of experiments, in which transfer of Debaromyces hansenii from human CD tissues, where it was present in intestinal wounds, into mouse models colonized injured intestinal areas and impaired wound healing. A mechanism of how Debaromyces hansenii may lead to wound healing abnormalities could be through interaction with myeloid cells.
This highlights that selective modulation of fungi in the intestine could improve wound healing in patients with IBD. What steps would need to be considered before this becomes a reality? Additional external validation would strengthen the findings of the selective presence of Debaromyces hansenii in CD. It could be worth exploring if a comparable phenomenon is also found in ulcerative colitis, the other entity of IBD, although it was present in colonic CD in this study and if Debaromyces hansenii can be found in different IBD phenotypes. Targeting selective portions of the intestinal flora remains a challenge and agents accomplishing this would need to be developed. This paper will likely trigger further studies with the aim to target the mycobiome to improve mucosal healing in IBD.
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