Most of the bacteria present in our gut and on our skin help us to combat disease. However, just as we were getting accustomed to how important bacteria are for people’s lives, another actor has arrived on the scene. New research shows that we may have given far too little priority to studying how fungi influence our bodies. They may prove to be at least as important to our health and well-being as bacteria.
Fungi diverged evolutionarily from plants more than a billion years ago and have since coevolved with animals as an integral part of all ecosystems – including people. Like bacteria, fungi therefore inhabit exactly the same barrier surfaces such as the skin and intestinal system. Although alterations and imbalances in the composition of fungi in the intestines have previously been associated with diseases such as inflammatory bowel disease, colorectal cancer and allergy, little has been known about the molecular mechanisms. Now, however, there has been a breakthrough.
“Ten years ago, we sought proteins that interact with one of nature’s most common substances: chitin. Chitin is abundant in our food: for example, in the skeleton of crustaceans and in fungi. Back then we found that chitin can bind to fibrinogen C domain-containing 1 (FIBCD1) protein. Our newest research shows that FIBCD1 is probably one of the keys to understanding how the human body interacts with fungi,” explains Jesper Bonnet Møller, Associate Professor, Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
Less fungi means reduced inflammation
Chitin is the second most common natural biopolymer in the world – only surpassed by cellulose. Researchers are very interested in how chitin affects people because chitin is a very important component of the cell wall of fungi. However, researchers have found little about how FIBCD1 interacts with chitin inside the human body.
“In our new research, we tried to determine how FIBCD1 affects the interaction between people and especially the fungi in our gut. To study this more closely, we examined people’s intestinal system to determine whether FIBCD1 is actually present there or whether it is mostly present elsewhere in the body.”
The measurements produced a clear result: FIBCD1 is mostly present in the membranes of the epithelial cells on the surface of the human gut. To investigate whether and how FIBCD1 responds to the presence of microorganisms such as bacteria and fungi, the researchers decided to investigate mice. Mice, unlike people, do not naturally have FIBCD1 in their intestines. Adding FIBCD1 had substantial effects.
FIBCD1 significantly affected the composition of the microorganisms in the intestines of mice. It did not apparently affect the quantity and types of bacteria. In contrast, the quantity of fungi declined considerably, and we specifically found that the number of especially dominant types of fungi such as Candida declined drastically.
To investigate whether the changes in the composition of fungi actually influenced the health and well-being of the mice, the researchers subjected the mice to an inflammatory condition in the intestinal system similar to ulcerative colitis – the inflammatory bowel disease that afflicts many people.
The mice that expressed FIBCD1 in their intestines differed notably from those that did not. The mice without FIBCD1 had much higher mortality. In addition, they lost significantly more weight and had a much stronger inflammatory reaction in the colon.
Major implications for health and disease
The new research may provide good news to people with inflammatory bowel diseases such as Crohn's disease and ulcerative colitis – diseases affecting an ever-increasing proportion of the population in our modern society. However, the reason for this increase is unknown. Most people have chitinases that can degrade chitin and several immune receptors that recognize chitin, causing the immune system to react.
We are trying to determine how these mechanisms interact with the molecular mechanisms of FIBCD1 and how they all contribute to developing intestinal diseases. Understanding this will enable us to develop new treatment options in the long term for the expanding group of affected people.
The new experiments have initially helped to identify FIBCD1 as a new and previously undescribed pattern recognition receptor that the human intestinal system uses to not only recognize but apparently also control colonization by fungi and thereby reduce intestinal inflammation.
“Although fungi only comprise about 1–2% of the human microbiome by number, the fungi are significantly larger than both bacteria and viruses. Their importance is therefore often underestimated.”
According to Jesper Bonnet Møller, the importance of fungi has not only been underestimated in connection with inflammatory bowel disease but also during antibiotic treatment, which can increase the quantity of fungi in the intestines.
I definitely think that the interaction between people and fungi is considerably more important than we previously understood. If we can learn to improve how our bodies control fungi, they can be crucial to improving our health and reducing disease.
“Modulation of the fungal mycobiome is regulated by the chitin-binding receptor FIBCD1” has been published in the Journal of Experimental Medicine. The Novo Nordisk Foundation awarded a grant in 2015 to Jesper Bonnet Møller for the project The Role of the Novel Chitin Receptor FIBCD1 in Inflammatory Bowel Disease and Helminth Infections and another grant in 2019 for the project FIBCD1-mediated Regulation of Intestinal Fungi in Inflammatory Bowel Disease.