Fungi play a critical role within our gut microbiome, research finds

Many fundamental scientific questions about the relationships between microbiomes and their hosts are unanswered. We know that bacteria in the microbiome are critical but there is little known about the role of fungi. Fungi have prominent roles in soil, marine, plant, and even food microbiomes. But what about the gut? Do gut fungi directly impact the microbiome, gut physiology and human immunity? 

A recent study by Dr. Marie Claire Arrieta, PhD, assistant professor at the University of Calgary’s Cumming School of Medicine (CSM), shows that fungi have a larger role in the development of the gut microbiome than we realized. The findings were recently published in Nature Communications. We sat down virtually with Dr. Arrieta (pictured above) to learn more about her research and what the findings mean.

Why did you want to study fungi?

There are not many studies done on the role of fungi in the gut microbiome. We had to start at square one and investigate the basics: What do fungi do? Where do they live in the gut and do they stay there? Do they change the microbiome? Do they react to antibiotics? Are they perceived differently by the immune system? By studying fungi, viruses, and other non-bacterial microbes, we hope to better understand the ecology and functionality of human microbiomes and their impact on disease.

How were you able to look only at fungi when there are so many bacteria in the gut?

Despite the simplicity in these questions, answering them posed an experimental hurdle: How can we tease apart the direct effects of fungi from those driven by bacteria in mixed communities? To leap over this hurdle, we use germ-free mice, which do not have any microbes in them, and then add either bacteria, fungi, or both. We know conditions have to be very controlled to avoid cross contamination, and we have the unique ability to do this type of germ-free research at the International Microbiome Centre (IMC).

The germ-free facility at the IMC at UCalgary has experimental suites that allow us to to introduce a select group of fungi (five types) and/or bacteria (12 types). This type of work is extremely time consuming — something that normally takes one person involves three people and three times as long. These sort of experiments can only be done in very few places in the world, so we are extremely lucky to have this facility here.

What sparked the idea of looking at the fungi?

I have been involved in microbiome research for a decade and have been mainly interested in studying the microbiome signatures in babies that later lead to asthma. A few years ago, I saw a presentation in a conference of a microbiome study that had including fungi, and asked myself why I wasn’t doing the same thing with fungi as I do with bacteria?

A lot of asthma research points to children and adults who develop asthma also being allergic to moulds. The question then lingered with me — is there a relationship between the change in the fungi that normally live in the gut, and what happens later in our immune system that makes someone more likely to get asthma? I still want to know for sure.

What did you find?

Our model shows that if fungi are present in the gut microbiome, not only did they shift the composition of the microbiome itself but also shifted different aspects of the immune system. For instance, the immune shift causes more severe colitis and increases the number of white blood cells in the airway, which is a sign of asthma. White blood cells are key to our immune response and critical to combat infections, but if too many are present for a non-infectious reason, they can cause uncontrolled inflammation.

In addition, we found conclusive evidence that yeasts are persistent gut dwellers, even in the absence of bacteria, although fungal diversity is favoured when bacteria are part of the community. We also discovered that fungi are pretty important members in the gut microbiome ecology and we think that their interactions are a big part of what shapes the ecosystem of the microbiome.

Lastly, our work provided causal evidence that fungi are important in early-life immune education, and the immune system does not develop the same way without fungi present. When both the bacteria and fungi are present, we found a synergistic effect that suggests they are both necessary for development.

What does this research mean for disease?

The ecosystem with or without fungi would look very different and this is why they are just as important as any other member of the microbiome in shaping that community — especially early in life. By further understanding the type of signals that our immune system ’senses’ in the fungi and bacteria that live in the gut, the easier it will be to investigate ways to prevent inflammatory disorders such as inflammatory bowel disease (IBD) and asthma.

Our work shows that overlooking fungi, which has been the norm for microbiome studies, misses part of these important signals coming from our gut. The characterization of these signals has great potential for prevention and treatment of many chronic diseases.

What is the your next research project?

We know that the gut microbiome helps dictate the way the immune system functions, and that this applies to how our bodies react to infections, including viral respiratory infections that are closely related with later asthma risk.  We want to take a closer look at this.

I would like to study how alterations to the gut microbiome in childhood, through antibiotics, for example, change the way children respond to viral respiratory infections. Before COVID-19, we were interested in studying the response to rhinovirus and respiratory syncytial viruses (very common respiratory viruses in babies) but of course now we want to also include SARS-CoV-2.

We are excited at the possibility of a  level-3 biosafety laboratory getting set up here at UCalgary, which will allow us to work with this new coronavirus. We know that alterations to the microbiome early in life and suffering viral respiratory infection increase a child’s risk to develop asthma, so with this work we want to understand how these two events are related.

Marie Claire Arrieta is an assistant professor in the departments of Physiology & Pharmacology, and Paediatrics, and a member of the Snyder Institute for Chronic Diseases and the Alberta Children’s Hospital Research Institute at the Cumming School of Medicine.