What is already known on this topic
Several studies have shown that human populations around the globe have different gut microbiotas. However, research that assessed how gut microbes affect health has tended to focus on individual populations, especially those from regions such as the United States and Europe. So, it’s unclear whether differences in microbiota composition can lead to differences in susceptibility to infection.

What this research adds
Researchers assessed the resistance to severe gut infection in germ-free mice that were colonized with the microbiota of people from the US, Fiji, and Guatemala. The team found that differences in the gut microbiota can influence the animals’ immune responses and thus their susceptibility to infection. Mice with microbiota from the Guatemalan population were the most resistant to infection, followed by rodents with gut bacteria from the US and Fiji populations. Housing mice together so that they shared gut bacteria helped the animals with low resistance to infection to become more resilient, the researchers found.

Conclusions
The ability to transfer resistance to infection suggests that the microbiota could be harnessed for therapeutic treatments. The findings also suggest that scientists should study the microbiota of different populations across the globe to draw generalizable conclusions about gut microbes and human health.

People around the globe have different gut microbiotas, and these differences may explain why some populations are more susceptible to intestinal infection than others, a study in mice shows.

The findings, published in Cell Reports, suggest that scientists should study the microbiota of different populations across the globe to draw generalizable conclusions about gut microbes and human health. 

“Across the world, you have a tremendous amount of diverse organisms in the gut microbiome. Those differences are way bigger than what we see in, for example, the US population,” says study senior author Ilana Brito at Cornell University. “There is a great need for understanding the specific causal roles those organisms play in health or promoting disease.”

Studies that assessed how gut microbes affect health have tended to focus on individual populations, especially those from regions such as the United States and Europe. So, it’s unclear whether differences in microbiota composition can lead to differences in susceptibility to infection. To fill this gap in knowledge, Brito and her colleagues set out to assess the resistance to severe gut infection in mice that were colonized with the microbiota of people from three different human populations.

Resilience to infection

First, the researchers transplanted stool from individuals from the US, Guatemala, and Fiji into germ-free mice. Two weeks later, the team infected the animals with Citrobacter rodentium, a mouse pathogen used to model infections with human enteropathogenic Escherichia coli

The team found that different gut microbiotas influenced susceptibility to infection. In particular, mice with microbiota from the Guatemalan population were the most resistant to infection, followed by rodents with microbiota from the US population. Animals with gut bacteria from the Fiji population were the most susceptible to infection.

The researchers found that the levels of specific immune molecules that trigger inflammation were elevated in the blood of mice with microbiota from the Guatemalan population. These mice also had higher levels of other inflammation markers in their stool compared to animals that received gut microbes from the US and Fiji populations. “You get very different immune responses of these microbiomes in these different mice that led them to be either more or less resilient to infection,” Brito says.

Global view

To assess if resistance to C. rodentium infection could be transferred through the gut microbiota, the researchers housed the three groups of mice together. Because mice eat each other’s stool, microbiota can be transferred from an animal to another, mimicking the way a person’s microbiota can change when they travel or change their diet. 

Housing mice together led animals with gut bacteria from the Fiji population, which had low resistance to infection, to become more resistant to infection, the researchers found. “It made the susceptible mice more resilient,” Brito says. “So, I think what these kinds of experiments showed us ways you can alter this immune background that comes from these bacteria in the gut, even on short time spans.”

The ability to transfer resistance to infection suggests that the microbiota could be harnessed for therapeutic treatments, the researchers say. However, Brito adds, “the broader point is that we should be studying the health effects of microbes that we find outside of our backyard. How could we improve people’s health with microbiome interventions throughout the world, for different types of health problems? It warrants a global view.”