Gut fungi are not as numerous as bacteria but their influence is likely larger
The fungal mycobiota: small numbers, large impacts (2016)
Immunological Consequences of Intestinal Fungal Dysbiosis (2016)
In a nutshell
Mouse gut fungi may be responsible for the shape of the bacterial population and host disease susceptibility
Mouse gut fungi affect changes in the bacterial microbiota population
Mouse gut fungi affect the mouse immune system in the gut and airways
Context
This article is prompted by an editorial entitled “The Fungal Mycobiota: Small Numbers, Large Impacts” [1]. It is a commentary on an article [2] in the same edition of the journal Cell Host and Microbe. I’ll be commenting on both papers in this brief update.
Objective and results of the investigation
The paper that prompted the editorial [2] investigated the effects on mouse immune function of disrupting gut fungi. It’s important to remember that studies in mice don’t always translate into humans but it’s at least a starting point.
The authors found the following:
Treatments that disrupt gut fungi, result also in disruption of the bacterial community
Disruption of the gut fungi worsened intestinal damage and allergic airway disease
Results support the notion that gut fungi are instrumental in affecting the bacterial population, mouse immune function and mouse inflammatory disease
Why is the paper interesting?
The accompanying editorial [1] lays out why this subject is important. They draw attention to the fact that gut fungi have “surprisingly strong effects on the immunological responses of the host” and gut fungi also affect the composition of the bacterial community.
The author goes on to state that these lines of evidence:
“…suggest that fungi are keystone species, i.e., organisms that have ecological impacts that far outweigh their numerical representation in the community.”
What is a keystone species?
In nature, keystone species have been defined broadly as:
“ ...species that exert extremely high influence on their surroundings relative to their population. Remove a keystone species, and the whole ecosystem is thrown off-balance; at best, it will be forced to adapt rapidly to new or invasive species taking over the habitat, and at worst – well, at worst, the ecosystem can cease to exist entirely.”
There are many examples of keystone species in nature. My favourite example of the unexpected consequences of a keystone species comes from Yellowstone Park where reintroduction of wolves benefitted the trout population.
“Simply relating bacterial microbiota to a disease state, as is the favoured approach presently, is a bit like trying to drive a car forward by looking in the rear view mirror.”
How does the paper help me to understand health and longevity?
Firstly, is it possible that fungi in the human gut are keystone species and, therefore, something we should take seriously? In a recent review [3] the authors state the following:
“…despite relatively small number of gut fungi, they profoundly affect nutrition, metabolism, and immunity in the intestine. Not only do intestinal fungi shape the functions of the gut, but they also affect the physiological functions of other crucial extraintestinal organs, such as the liver, lung, and brain”
To my mind, they are essentially saying the same as the original authors I’m reporting [2], without going quite as far as to state that fungi are a keystone species in the gut microbiota [1].
When we look outside humans, it appears that the soil microbiome contributes to and shapes the human gut microbiome [4]. It also appears that in soil, fungi act as keystone species [5]. So, yes, I am prepared to believe that fungi may well act as mammalian, including human, gut microbiota keystone species.
I have long wondered about the state of human microbiome research and how ready we are to state with confidence how to interpret existing microbiome data and use manufactured microbiota and microbiome products therapeutically. This paper has nudged me towards concluding that we are not yet ready to do either broadly and with confidence.
If, as seems likely, gut fungi are directly affecting the human immune response (for example) and the nature of the bacterial population, we need to be aware of the gut fungal population in order to understand the state of the bacterial microbiota and the root cause of a disease. Simply relating bacterial microbiota to a disease state, as is the favoured approach presently, is a bit like trying to drive a car forward by looking in the rear view mirror.
Study outline
It’s important to remember that the study [2] was conducted in mice, 8-10 weeks of age. The effects of anti-fungal treatment and seeding with certain fungal species was investigated in models of intestinal and airway inflammation. Standard, validated assays were employed throughout.
Full details are provided at the end of the paper.
References
C.A. Kumamoto The fungal mycobiota: small numbers, large impacts. Cell Host Microbe, 19 (2016), pp. 750-751
Wheeler ML, Limon JJ, Bar AS, Leal CA, Gargus M, Tang J, Brown J, Funari VA, Wang HL, Crother TR, Arditi M, Underhill DM, Iliev ID. Immunological Consequences of Intestinal Fungal Dysbiosis. Cell Host Microbe. 2016 Jun 8;19(6):865-73. doi: 10.1016/j.chom.2016.05.003. Epub 2016 May 26. PMID: 27237365; PMCID: PMC4900921.
Wu, X., Xia, Y., He, F. et al. Intestinal mycobiota in health and diseases: from a disrupted equilibrium to clinical opportunities. Microbiome 9, 60 (2021). https://doi.org/10.1186/s40168-021-01024-x
Blum WEH, Zechmeister-Boltenstern S, Keiblinger KM. Does Soil Contribute to the Human Gut Microbiome? Microorganisms. 2019 Aug 23;7(9):287. doi: 10.3390/microorganisms7090287. PMID: 31450753; PMCID: PMC6780873.
Shaeldake, M. (2020) Entangled Life: How fungi make our worlds, change our minds, and shape our futures. London: Bogley Head