Diverse bacterial species colonize the human gut and offer important health benefits. Gut microbiota has been found to provide colonial resistance, and multiple mechanisms influence such ability. However, these mechanisms are context-specific and depend on particular species of bacteria. Experts lack general principles to predict the microbiota communities that can protect against pathogens.

Collective Protection from Gut Bacteria

Researchers from the Departments of Biology and Biochemistry at the University of Oxford investigated the diverse communities of resident bacteria, focusing on their ability to protect the human gut from disease-causing microorganisms. Their findings are discussed in the paper "Microbiome diversity protects against pathogens by nutrient blocking."

Led by Professor Kevin R. Foster, the researchers used an ecological approach in investigating 100 different gut bacteria strains, testing them individually and in combination. They were examined regarding their ability to limit the growth of two harmful bacterial pathogens, Klebsiella pneumoniae and Salmonella enterica.

It was found that individual gut bacteria demonstrate a very poor ability to restrict the spread of either pathogen. Meanwhile, communities of up to 50 species cultured together led the pathogens to grow up to 1000 times less effectively. The 'community protection effect' was observed regardless of whether the bacteria were cultured together in vials or in 'germ-free' mice, which do not contain resident gut bacteria at the start of the experiments.

According to Professor Foster, the results demonstrate that colonization resistance is a collective property of microbiome communities. In other words, a single gut bacterial strain is protective only when combined with different songs.

However, the analysis also indicates that the members of the bacterial communities, and not just the overall diversity, significantly affected the level of protection. Certain species were potentially essential for community-based conservation, even if these species provided little protection on their own.


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Nutrient-Blocking Mechanism

It was also revealed that protective bacterial communities block pathogen growth by consuming the nutrients needed by the pathogens. Professor Foster and his colleagues assessed the bacterial species' genomes, and found that the most protective communities consist of species with protein compositions highly similar to the pathogens. Metabolic profiling also demonstrates that the protective species had similar demands for carbon sources as the pathogenic species.

While increased microbiome diversity improves the probability of protection against pathogens, there is an overlap in nutrient utilization profiles between the protective community and the pathogens. Some species with an important role in community protection show a high degree of metabolic overlap with the pathogenic species, demonstrating similar nutrient demands.

The researchers used this nutrient blocking principle in predicting bacterial communities that would provide weak and strong protection against a different pathogen, the antimicrobial-resistant Escherichia coli strain. Experimental tests revealed that communities with the highest nutrient overlap with the E. coli strain were up to 100 times more effective at reducing the abundance of pathogens.

Such a mechanism could explain why some individuals become more susceptible to species like K. pneumoniae after taking antibiotic drugs that are supposed to lower the diversity of microbiome species. The researchers believe this new insight can be developed into new strategies for fighting harmful gut pathogens by optimizing gut microbiome communities.

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