Our gastrointestinal tract is teeming with microbes. The community of microbes that live in our gut, known as the gut microbiome, is crucial to our health and mental well-being.

The gut microbiome is comprised of archaea, bacteria, viruses and fungi. While we know lots about the bacteria and viruses living in the gut microbiome, we know far less about the fungi found there.

The fungal component of the microbiome is known as the mycobiome.

Candida albicans from a MOTION sample. Credit: Dr Steve James with QIB Advanced Microscopy Facility.

Finding fungi in the gut

When you look at the gut microbiome, in terms of cell numbers, fungi make up just a small proportion of all the microbes living there. Less than 1% of the gut microbiome is probably fungal, compared to more than 99% that is bacteria and viruses.

Although there are far less fungi in the gut microbiome compared to other microbes, they are much bigger than bacteria and viruses.

Given their size, fungi are likely to constitute a sizeable proportion of the overall intestinal microbiome biomass. So, despite their low numbers, fungi can have significant impact on human health.

One area of microbiome research I am especially interested in is fungal genome sequencing. Generally, in scientific research, there is plenty of bacterial and viral sequencing of the gut microbiome but less so of the mycobiome.

This is partly because there is much less fungal DNA in the gut, so it can be trickier to find and sequence.

Often, we use metagenomics to study the gut microbiome, sampling DNA which is a complex mix of DNA sequences from a diverse array of microorganisms. 99% or more of this metagenomic DNA will be bacterial, so looking for the fungal component is comparable to looking for a needle in a haystack.

At the Quadram Institute, we’re perfectly placed to find out more about the fungi living in our gut by sequencing fungal DNA. We’ve got the skillset, the sequencing facility, and the bioinformaticians.

Where do fungi in our guts come from?

At the moment, we’re trying to identify the core resident fungi found in the human gut. This is challenging, given that fungi are quite literally everywhere.

This means that while we may find fungal DNA sequences in the gut, much of it might originate from fungi that are simply passing through our gastrointestinal tract rather than living there permanently.

This may be particularly true in regions like Norfolk, where we can get fungal spores from agriculture. We can ingest these airborne spores, and they can be subsequently detected in the gut. Indeed, I’ve found sequences from plant-associated fungi in human gut samples. However, when you look closer at their biology, you discover many of them can’t grow at 37°C, the normal human core body temperature. So, it’s highly unlikely that such fungi are going to colonise and take up residency in the human gut. They are transient – quite literally passing through.

Diet also has a major influence on our intestinal mycobiome.

Beer, bread and wine are all great sources of ingesting the yeast Saccharomyces cerevisae. Cheese, especially blue cheeses like Stilton, are a good source of Penicillium roqueforti. Some of these fungi can grow at 37°C, so in theory they might be living in our guts. But it’s an ongoing research question to establish whether or not they are transient or long-term intestinal residents.

There are some fungi that we are confident are long term residents in our gut. A common member of the human gut mycobiome is Candida albicans. This fungus is found in around 40-60% of healthy people in the Western World.

You generally acquire Candida albicans from mum, passed from mother to baby during birth, by a process known as vertical transmission. It’s quite difficult to find it in the environment and is rarely found in our diet, so it’s now well accepted as an authentic gut fungus.

The mycobiome and health

Fungi, just like bacteria, can affect our health in both positive and negative ways.

For the majority of people, for most of the time Candida albicans is a benign member of the microbial gut flora. But if you are immunocompromised in some way or receiving prolonged antibiotic treatment, then this fungus can quickly switch from being a ‘friendly’ microbe to one that causes disease.

Candida albicans has the ability to switch its shape from a classical yeast shape into a filamentous (hyphal) form. Research has shown that the fungus becomes pathogenic and causes disease when it enters this invasive filamentous stage of growth. However, we believe that some of the resident gut bacteria produce metabolites that can prevent filamentous growth and help keep the fungus in check. We’re hoping to look at this in greater detail and tease out some of the underlying mechanisms.

I worked on a collaborative project with Professor Lindsay Hall looking at the gut mycobiome of preterm infants . What we discovered was that Candida albicans, along with a close relative Candida parapsilosis, were common members of the gut microbiome of these young infants. With its innate ability to form biofilms on medical devices such as catheters, Candida parapsilosis poses a serious threat to preterm neonates, particularly if it gets into their blood stream.

Furthermore, recent research has revealed that often Candida parapsilosis blood stream infections appear to originate from the host gut.

Within Professor Simon Carding’s group, we have shown in mice that a human-derived clinical isolate of Candida albicans could escape from the murine gut and translocate via the bloodstream to the brain and cause cerebral inflammation.

If a fungus, like Candida albicans is causing disease it can prove difficult to treat. Compared to a bacterial-derived infection, there are less treatment options available. You can’t use antibiotics to treat a fungal infection, you need to use antifungals and there are fewer of them.

This is partly because fungi, like us humans, are eukaryotes, meaning their cells have nuclei. Lots of antibiotics target bacteria because they are prokaryotes, meaning their cells do not have nuclei. So, it’s harder to find treatments that are specific to fungi, without having consequential side effects for the human host.

Flying the fungal flag in microbiome research

There’s lots to learn about what a healthy gut mycobiome is, and how it interacts with us as the human host.

I started my research career working in the National Collection of Yeast Cultures on yeasts involved in food spoilage. Around five years ago I joined Professor Simon Carding’s group and started to research fungi living in the gut. Through human studies like the MOTION, BAMBI and PEARL studies we have been learning more about what fungi live in the gut and how they affect our health.

There is now far more research on the gut mycobiome, compared to when I began working in this field five years ago.

Here at the Quadram Institute, the Hildebrand group are using metagenomics to study the gut microbiome including the fungal component. Meanwhile Bushra Schuitemaker is researching the gut microbiome of chickens, including the mycobiome. In the Carding group, in collaboration with colleagues from UKHSA, we have also found how the gut mycobiome of non-human primates differs quite markedly in its composition compared to that of humans.

I’m currently working with Professor Arjan Narbad’s group on yeasts in fermented foods and how they might affect our health. Another area of future interest relates to plant-based diets and how these may affect the compositional make-up of the gut mycobiome.

More widely, we benefit from the Norwich Research Park being a hub for microbiology. There are over 300 microbiologists here on the research park working on archaea, bacteria, fungi and viruses.

At the Quadram Institute, we’re the perfect place to discover more about the gut mycobiome.