While most microbiome scientists focus on gut bacteria, a new school of research is starting to look at how the communities of fungus in our bodies, called the mycobiome, can influence our metabolic health. A newly published animal study suggests fungal diversity may play a role in weight gain.
Trillions of micro-organisms live inside each of us. This is our microbiome. The vast majority of these microbes are bacteria. Arguably one of the most significant areas of medical research over the past couple of decades has been the growing understanding of a symbiotic relationship between our general health and the bacteria we house.
Most microbiome research has focused on gut bacteria, however, there are other microbes that call our digestive system home including parasites and viruses. Less than 10 years ago, a landmark study was the first to definitively show a rich community of fungi also live in our microbiome.
Dubbed the mycobiome, this fungal community was hypothesized to influence immune and metabolic health in ways similar to gut bacteria. The 2012 study suggested ulcerative colitis in mice can be influenced by fungi interacting with innate immune receptors.
If research into the effect of gut bacteria on human health is young, then work on the mycobiome is in its infancy. Investigations into our fungal friends are so minimal some scientists still question whether the human mycobiome is simply controlled by diet, or whether it is a collection of more commensal organisms living and replicating symbiotically within us in ways similar to that of the bacterial microbiome.
A new study, published in the journal Communications Biology, set out to investigate some of these questions. Does the unique composition of the mycobiome affect an organism's metabolism? What causes genetically identical organisms to develop unique mycobiome populations?
The first step in the new research looked at genetically identical mice, obtained from four different vendors. All four groups of mice displayed significantly different mycobiome populations. This affirmed that despite the genetic similarities, baseline fungal mycobiome differences appear as variable as bacterial microbiome differences.
The researchers then fed the animals either standard chow or a diet similar to a high-sugar, high-fat western diet full of processed foods. The goal was to examine how fungal populations influenced metabolism over time in a cohort of genetically identical animals.
While the mice fed the processed food diet quickly and unsurprisingly gained weight, the level of weight gain varied depending on the animals’ baseline fungal mycobiome composition. Other differences in metabolic markers, such as gene expression in various tissues, also correlated with mycobiome composition.
“We found that mice whose gut microbiomes contained more of the fungi Thermomyces – which manufacturers use to break down fat in commercial processes – and less Saccharomyces – yeasts used in baking and brewing – gained about 15% more weight than the mice with different microbiomes. We found similar but smaller differences in mice on a normal diet,” write two of the researchers, Kent Willis and Justin Stewart, in a recent piece for The Conversation.
Needless to say it is very early days for research into the mycobiome. Little is known, for example, about how fungal species initially populate an organism. A 2017 study found a number of fungal species in mice did not come from chow fed to the animals.
This suggests the mycobiome is acquired and influenced by a number of environmental sources. Plus, it still is a mystery which fungal species persist in the gut over time, or how age-related factors influence the mycobiome over an organism’s lifetime.
Joseph Pierre, co-corresponding author on the new study, suggests his research adds yet another complicating factor into the increasingly complex mix of variables influencing gut bacteria research. It may be unclear at this stage what role fungi play in the relationship between the microbiome and its host’s metabolism, but what is clear is that fungal populations are certainly influenced by both diet and environment. And disruptions to fungal populations can correlate with metabolic changes.
"Our results highlight the potential importance of the gut mycobiome in health, and they have implications for human and experimental metabolic studies," says Pierre. "The implication for human microbiome studies, which often examine only bacteria and sample only fecal communities, is that the mycobiome may have unappreciated effects on microbiome-associated outcomes."
A few years ago a team of researchers in the United States set out to catalog all the genes in the collective human microbiome. The first study to come out of the research, published in 2019, chronicled 46 million genes from just a few thousand human microbiome samples.
Half of those genes are unique to single human samples. The researchers described the genetic diversity in their findings as "staggering". An open-source database called The Universe of Microbial Genes was established.
The scale of genetic diversity seen in the microbiome is described as akin to the amount of stars in the observable universe. Even the most conservative estimates suggest there could be at least 230 million unique genes in the human microbiome.
Alex Kostic, from Harvard Medical School and a co-author on that 2019 study, says the astronomical array of differences from one person's microbiome to another's means any future medical therapy will need to be highly targeted to each individual.
"Such narrowly targeted therapies would be based on the unique microbial genetic make-up of a person rather than on bacterial type alone," said Kostic in 2019.
Adding a whole universe of fungi to the mix certainly makes microbiome research exponentially more complicated. Several recent mycobiome review articles point to the need for understanding fungal-bacteria relationships as this understudied interplay may play a role in human health.
Looking forward, the next steps for the researchers behind this new study will be to further investigate the links between metabolism and the fungal mycobiome. Willis and Stewart hypothesize the intimate functional relationship between fungal communities and bacteria may fundamentally influence how our microbiome affects our metabolism.
“We are planning to perform studies in humans and mice looking at how the fungal microbiome influences metabolism on high-fat diets and after weight loss surgery,” the pair of researchers write. “And to learn more about how different fungi affect metabolism, we’d like to create mice with artificial microbiomes that we either assemble ourselves or transplant from a human donor.”
The new study was published in the journal Communications Biology.
Source: University of Alabama at Birmingham, The Conversation
