This group of bizarre gut microbes is unexpectedly complex
Alongside the bacteria, fungi and other organisms living in our guts are single-celled, nucleus-bearing microorganisms called protists. A study in mice — whose protists are related to some found in humans — now shows how these under-studied organisms’ food preferences shape competition with other organisms in the microbiome and affect their host’s immune responses.
The work, published on 13 December in Cell1, illuminates differences between the species of protist living in the gut and highlights a growing appreciation for their impact on health.
Protists are often considered “fourth-class citizens amongst microbes, and they shouldn’t be”, says microbiome researcher Seth Rakoff-Nahoum at Boston Children’s Hospital in Massachusetts. The research “really, really shines a light on their importance”, he says.
Mysterious microbes
Past research has shown that gut protists can activate immune responses. In mice, for example, the single-celled organism Tritrichomonas musculis excretes the molecule succinate, which kicks off an immune response in the small intestine called type 2 immunity2. The protist also boosts the number of immune cells called T helper 1 (TH1)3 and T helper 17 (TH17)4 — which send signals to other immune cells — in the colon. But little is known about gut-protist diversity, their metabolism or how they interact with other microbes.
A team led by mucosal immunologist and microbiome researcher Michael Howitt at Stanford University in California screened laboratory mice to find out what protist species might be living in their guts. They identified a species similar to T. musculis, which they named Tritrichomonas casperi. A search of DNA data from human faecal samples hinted that close relatives of these two species live in some people.
Experiments comparing the species showed that, like T. musculis, T. casperi triggers the production of TH1 and TH17 cells in the gut. But the newly described species doesn’t excrete succinate and is the only mouse gut protist in the genus Howitt has ever encountered that doesn’t activate type 2 immunity in the small intestine. “That was the first thing that really got me to sit up and take notice,” he says.
Dietary requirements
This finding led the researchers to explore other differences between the species. Gut microbes often rely on foods eaten by the host — such as plant fibre — but can also consume other resources in the gut, including the mucus secreted by intestinal cells. Feeding mice different foods suggested that T. musculis prefers dietary food sources, whereas T. casperi likes intestinal mucus.
Mice with just T. musculis in their guts also had fewer fibre-eating bacteria in their guts than did control mice with neither protist species, and mice with only T. casperi had low levels of mucus-consuming bacteria. This suggests that in each niche, protists compete with bacteria — and usually win. Furthermore, the researchers found that the availability of different food sources, including mucus, can influence some of T. musculis’s effects on type 2 immunity.
Howitt hopes that this paper will inspire other microbiome researchers to consider protists in their work.
“There has been a tendency to pigeonhole these protists as little swimming bags of succinate,” he says. But “there are clearly a lot of other things that they’re doing and other ways that they can influence the gut ecosystem and gut health”.
doi: https://doi.org/10.1038/d41586-023-03990-8
References
Gerrick, E. R. et al. Cell https://doi.org/10.1016/j.cell.2023.11.018 (2024).
Nadjsombati, M. S. et al. Immunity 49, 33–41 (2018).
Escalante, N. K. et al. J. Exp. Med. 213, 2841–2850 (2016).
Chudnovskiy, A. et al. Cell 167, 444–456 (2016).
