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It's time to highlight our fungus friends in our microbiomes

Our gut microbiomes contain fungi and protists, not just bacteria - so why don't we study them?

Our gut microbiomes are made of millions of tiny microbes, such as bacteria, fungi, and protists, which perform services like helping us digest food and protecting us against certain infections. If fungi and protists are microbes too, why have they largely been left out of gut microbiome research, which has focused instead almost solely on bacteria? Microbes interact in our gut environment in ways that we yet don’t fully understand. And the only way that we will begin to is by bringing fungi and protists into the research mix

Electron micrograph of Escherichia coli, from the US Department of Agriculture (USDA) Agricultural Research Service (ARS).

E. coli, a bacteria that commonly makes us sick

USDA ARS

Bacteria are single-celled organisms that are invisible to the naked eye and very abundant in our guts. They get a lot of attention because they cause disease and death. But focusing solely on this one facet of the microbiome contributes to the misconceptions that only bacteria inhabit our guts and that bacteria are exclusively what gut microbes should look like. Such fallacies are driving dangerous trends that aren’t backed up by science, like DIY fecal transplants. Ignoring that our guts are complex environments inhabited by a plethora of microbes in favor of quick home remedies can lead to serious life-threatening situations, like transplanting antibiotic resistant organisms and viruses, such as HIV and hepatitis.  

Fungi and protists can be single-celled and microscopic too. They are also abundant in our guts, and cause a lot of diseases in humans, although they are rarely marked as health threats. Regardless, fungi, protists, and bacteria inhabit the same spaces in our guts and share and compete for resources. And even though studying all members of the microbiome is extremely challenging, it is the only way that we will begin to understand the complex interactions among them and do better science.

By studying both fungi and bacteria in the gut microbiome of people with Crohn’s disease, for example, a chronic inflammation of the gastrointestinal tract, scientists found that people with Crohn’s had less bacteria and more fungi in their gut compared to people without the disease. In fact, there is evidence showing that Crohn’s disease flare ups, which is a sudden intensification of symptoms, are directly related to the increase of fungi in the gut. People with types 1 and 2 diabetes show similar trends, hosting more fungi in their gut compared to non-diabetic people.

But as of right now, it is unclear whether these changes between fungi and bacteria in the gut microbiome are simply the result of disease progression or if these changes actually play a crucial role in disease onset. The case of protists is even worse - they aren’t even considered yet in most gut microbiome studies. But understanding the dynamics of fungal and protist gut communities is key in figuring out what role our microbiomes play in disease onset and progression.

mushrooms on a log

Don't forget about us!

Kitty Terwolbeck

Right now, interpretations of gut microbiome studies should be taken with caution. We cannot make any major assumptions about the gut microbiome and its association to diseases, or how to treat them, until we have a better understanding of how every microbial group in the gut microbiome behaves individually and how they interact. Even though there are a lot of interesting health trends associated with the bacteriome, there are also potentially millions of fungi and protists that are being ignored. It's time to investigate them.

Comment Peer Commentary

We ask other scientists from our Consortium to respond to articles with commentary from their expert perspective.

Molly Sargen

Bacteriology

Harvard University

Thanks for sharing this perspective, Adriana. As a microbiologist focusing on bacteria, I’m definitely guilty of having tunnel vision to other microbes. This an issue for other fields of microbiology too and something the community as a whole needs to improve. It’s especially important to be considering diversity in metagenomic studies. When DNA is isolated from the microbiome (or any other environmental source), scientists can’t selectively isolate bacterial or fungal DNA. Likely, data about fungi and protists in the microbiome is already available and waiting for someone to use it with an inclusive perspective. Whether talking about fungi, protists, or even bacteria, I don’t think we know enough to make treatment decisions based on the microbiome  yet. It’s hard to understand an individual organism in a laboratory environment, let alone a population of interacting organisms in an environment we can’t easily access. 

Adriana Romero-Olivares responds:

I agree! I think that to begin with, a change in wording is a good place to start. If you’re only studying bacteria, say “bacteria”, not “microbes”; same for fungi, same for protists. And I agree that we’re very far away from doing diagnosis based on the gut microbiome, same for  ecosystem-scale microbial mediated processes, which is my area of expertise. Thank you! 

Molly Sargen responds:

That is a great idea! I will try to incorporate this more. 

Laetitia Meyrueix

Nutrition and Epigenetics

University of North Carolina - Chapel Hill

Great article! You are highlighting something very important and something that is not talked about when considering these microbiome studies. I recently took a seminar on microbiome research and we did not discuss this whatsoever. Many of the nutrition-focused microbiome studies use 16S sequencing which is specific to bacteria and thus makes it impossible to capture our fungus friends. However, there are some who have done shotgun sequencing, which like Molly is suggesting, would offer the opportunity to expand upon the human microbiome research. Considering the current state of microbiome research, I think what you are highlighting will offer some possible answers to a field with many questions and add a lot more questions that need answering. But as you say, we cannot consider bacteria, fungi, and protists as independent of each other if we want to get to the bottom  of this. They function together as a community and so thus need to be considered as such. 

Adriana Romero-Olivares responds:

I understand that using more than one marker is very challenging, and with metagenomics, which is our best bet right now, the pipelines are so intimidating. And the “friendly pipelines” like MG-RAST are so heavily biased towards bacteria that even if we use them to analyze the  community as a whole, we’re probably still missing out on a lot of microbes and what they’re doing. At least for fungi, the databases are slowly growing, so it’s a matter of time before we do inclusive microbiome work!  

Lauren Sara McKee

Microbiology, Biochemistry, and Agricultural Science

KTH Royal Institute of Technology

Adriana, this is a great read and a much needed perspective. All of the non-bacterial species in the gut have been sorely overlooked, and you’ve highlighted some examples where this can be dangerous.

I have enjoyed some articles, such as these published a while ago in EMBO and Microbiology & Molecular Biology Reviews, that point to this problem and suggest ways of changing our thinking about the gut microbiome. In microbial ecology, still very much an environmental rather than a medical science, microbes are studied in terms of how they relate to and interact with each other, as well as the biogeochemical  elements of their surroundings. We need to find ways to integrate terminology and modes of thinking from classical microbial ecology into the very modern era of microbiome study, or we’ll continue to miss important insights such as those you point out in your article here.

Adriana Romero-Olivares responds:

I totally agree with you! I’m a microbial ecosystem ecologists and I’m baffled by the stats and experimental set up of many microbiome studies… many of them are not right. At the same time I don’t do anything to communicate with scientists doing microbiome  biomedical research to try to change this. The paper looks really interesting I’ll take a look! Thanks for sharing! I also enjoyed reading this perspective a lot.

Lauren Sara McKee responds:

Thank you for the link! This is ideal, could be really helpful in integrating microbiome studies with microbial ecology. 

Juliann Tefft

Biomedical Engineering

Boston University

Interesting article, I think this is a huge gap in the field of microbiome research at the moment.

Since you cited studies regarding microbial shifts in Crohn’s  disease, I think it is worth mentioning a study that came out in Nature last month which provided a year long multi-omics study of the gut microbiome of patients with Crohn’s disease through the Integrative Human Microbiome Project.

In the study they focus primarily on bacterial loads, similar to your criticisms above, but they share a huge amount of data in the supplementary information including the observation of a spike in viral load preceding microbial dysbiosis. Additionally, they include data showing that subjects with dysbiotic Crohn’s disease have higher titers of anti-yeast antibodies, further highlighting your point that studying the microbiome in a more holistic manner is likely essential to moving forward as a field.