Certain yeasts are a potential trigger for chronic inflammatory bowel diseases such as Crohn’s disease. This applies to some fungi that are part of our intestinal flora as well as to fungal species that are consumed through food, and opens up new therapeutic approaches against chronic intestinal inflammation.
In a recent study, a research team from the Medical Faculty of the Christian Albrechts University in Kiel and the University Hospital of Schleswig-Holstein investigated which microbes in our intestines can trigger chronic intestinal inflammation. Certain yeast fungi have been identified as an important factor. The corresponding study results are published in the specialist magazine “Nature Medicine”.
What role does the intestinal flora play?
Misguided reactions of the immune system to microorganisms in the intestine have been discussed by experts for a long time as a potential trigger for chronic intestinal inflammation, and last year researchers at the University of California San Diego School of Medicine were able to identify certain intestinal bacterial enzymes as triggers for chronic intestinal inflammation for the first time.
However, it remains largely unclear which microorganisms trigger the misdirected immune response and exactly how the immune cells react. The German research team therefore tried to clarify these questions.
Interaction with the immune system
Trillions of microorganisms colonize the human body and especially the intestines, with fungi playing a smaller role alongside viruses and bacteria. The researchers explain that these microorganisms live in symbiosis with the human organism and are essential for its healthy functioning.
The immune system has the important and at the same time difficult task of interacting with the microbiome so that the microbes are tolerated but at the same time kept in check. However, this interaction is apparently disturbed in the chronic intestinal inflammation Crohn’s disease.
In people with Crohn’s disease, the immune cells react too strongly to certain components of the intestinal flora and inflammation in the intestines flares up again and again, which is accompanied by symptoms such as pain, diarrhea, fever and other symptoms, the researchers explain.
What role do microbes play in Crohn’s disease?
The so-called T cells are particularly important in this immune reaction and “we wanted to find out which microbes trigger an altered T cell reaction in Crohn’s disease,” explains lead author Gabriela Rios Martini.
To do this, the researchers analyzed the reaction of certain T cells to various microbes in blood and tissue samples from patients with Crohn’s disease compared to healthy people.
“We first examined the reaction to certain bacteria, as these make up a large part of the microbiome, but we were unable to detect any differences between sick and healthy people with the species examined so far,” reports Rios Martini.
Strong reaction to yeast fungi
However, when examining T cell responses to yeast fungi, such as various Candida or Saccharomyces species, the researchers surprisingly observed a massively increased T cell response in Crohn’s disease patients.
This applied both to yeasts that were part of the natural, healthy microbiome and to yeasts that are primarily ingested through food.
The sequencing of the T cells that reacted to the yeast fungi showed that sick people mainly contain T cells whose T cell receptors can react against many different Candida and Saccharomyces species.
“Apparently the T cells specifically recognize a certain part in these related yeast fungi that occurs in many of the species examined,” said study author Professor Petra Bacher. This means that the T cells not only react to a specific yeast species, but can be activated by many different Candida and Saccharomyces yeasts.
“Overall, our data indicate that after an initial T cell reaction against yeast fungi, repeated contact with antigens found in several yeast fungi leads to the activation and proliferation of cross-reactive T cells,” explains Bacher.
The immune reaction is probably triggered again and again, which probably also contributes to the chronicity of the inflammation. In addition to the so-called commensal yeasts that live in the intestines, the yeasts consumed daily from food could also play a role.
New therapeutic options
However, the researchers also have good news, because “the findings lead to possible new therapeutic approaches,” says study author Professor Stefan Schreiber. Further studies are now investigating the effects of avoiding yeast in the diet or eliminating yeast in the intestine through anti-fungal therapy.
Another approach could be to specifically incapacitate the cross-reactive yeast-specific T cells using cellular therapies. Further studies must show whether such new therapeutic approaches, which directly target the yeast fungi in the intestine or the yeast-specific T cells, are effective.
Overall, yeast fungi have apparently received far too little attention in the mechanisms underlying the development of chronic inflammatory bowel disease and the new study provides strong evidence for the first time that yeast-reactive T cells are involved in the inflammatory reaction in Crohn’s disease. This is an important step in understanding the disease. (fp)