Gut bacteria are stronger together when it comes to preventing infectious diseases.
When a large, diverse community of gut bacteria compete with pathogens for nutrients, the pathogens may not have enough fuel to colonize and invade the body, according to a new study in Science.
The more microbes there are, the more different nutrients they're likely to eat, increasing the chances of nutrient overlap with the pathogen. The greater the overlap, the better the host is protected, the study found.
"The nutrients available to the pathogen are limited," said lead study author Frances Spragge, a researcher in the department of biochemistry, University of Oxford, Oxfordshire. "So, its invasion is blocked."
It makes sense, said Thomas Schmidt, PhD, professor of microbiology and immunology at the University of Michigan, Ann Arbor. (Schmidt was not involved in the study.) "It's kind of no surprise that competition for resources is what is providing the colonization resistance," Schmidt said. "But we didn't have evidence that that was the case."
The study is among the first to take a systematic approach to addressing competition between pathogens and specific host microbes, Schmidt said. It's a step toward identifying microbes that could be useful in treating infections.
What the Researchers Did
In test-tube experiments, the researchers screened 100 common strains of human gut bacteria, pitting each one against two bacterial pathogens: Klebsiella pneumoniae and Salmonella typhimurium. Both pathogens — which cause pneumonia and food poisoning, respectively — can become resistant to antibiotics.
Though some strains blocked pathogen growth better than others — Escherichia coli performed the best — none alone could prevent colonization. But when researchers pooled the top 10 best pathogen-fighters, protection was much more robust. Combining 50 species worked better still, if these included E coli.
Testing in mice showed similar results. Researchers colonized germ-free mice with varying numbers of bacterial species and then exposed the rodents to the pathogens.
"Increasing the number of species in the community tended to increase the communities' protectiveness," Spragge said. However, "it was also crucial that certain key gut species were present."
Compared with other species, these "key" species (E coli among them) consumed more of the same nutrients as the pathogens, the researchers discovered. Individually, they did not have enough overlap to stop pathogen growth — but communities including these strains had the highest overlap and provided the best protection.
Why It Matters
Though much more research is needed, these findings could pave the way for microbiome-based treatments for infectious diseases, the researchers said.
"We could use this nutrient blocking effect to make and successfully validate predictions about which combinations of gut bacteria would be most protective against a given pathogen," Spragge said.
As more and more is being revealed about the microbiome, interest in microbiome-based treatments is growing. A year ago, the US Food and Drug Administration approved the first fecal microbiota product (Rebyota) to prevent recurrence of Clostridioides difficile infection in adults. An oral microbiota treatment (Vowst) was approved in April.
With methods like the ones used in this study, similar treatments could be refined to include microbes that compete with C difficile, Schmidt said. And other treatments could be developed to target other pathogens.
Advances in genomics can help us know what bacterial species a person has in their microbiome, Spragge said. Someday, with more research, doctors could potentially use that information to figure out what species patients need to prevent or fight an infection.
For now, the study is a reminder to recommend a diet high in fiber (to promote gut health), Schmidt said, and to minimize unnecessary antibiotic use, Spragge said. "Antibiotics are known to reduce microbiome diversity, and there is an association between taking antibiotics and the risk of infection by bacterial pathogens," said Spragge.
Christina Szalinski is a freelance science writer with a PhD in cell biology based in upstate New York.
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