Undeveloped immune systems are not the only culprit in infants’ susceptibility.
The microbiome is a diverse community of organisms living in a single environment, including environments like the bodies of larger animals. In humans, the bulk of the microbiome is in the intestines, where these tiny organisms help us digest food and regulate some of our body’s responses to our diet. However, studying the microbiome in humans is challenging for practical and ethical reasons. As a result, mice have the most widely studied mammalian microbiomes.
The recent Science paper provides new insights into how the microbiome interacts with a mouse’s ability to resist infection. For this study, germ-free adult mice were given a transplant of gut contents from either neonatal mice, adolescent mice, or adult mice. The transplant came from the first few inches of the large intestine/colon, so this transplant process was not dissimilar to a stool transplant (more commonly known as a poop transplant). These transplants altered the gut microbiome of the recipient so that it matched the donor mouse’s.
After giving the poop transplants three weeks to spread through the guts of the recipient mice, the researchers examined the biodiversity in the recipients’ intestines. They found more biodiversity in the microbiome of the mice that received transplants from either adolescents or adults than they did in mice that received transplants from pups.
A diverse microbiome has been associated with an ability to resist harmful infections. This suggests that mice that received transplants from older donors may be better able to resist pathogens. To test this, the researchers infected the recipient mice with a strain of salmonella, looking for differences in resistance and survival based on the age of the transplant donor. All of the mice that received transplants from adult mice survived the salmonella infection. By comparison, only half of the mice that received transplants from pups survived.
Because all the recipient mice were adults, they should have had immune systems that were fully developed. Therefore, the difference in survival rate can be linked almost directly to the difference in the transplant donors’ microbiomes. When the authors looked more closely at the intestines of the recipient mice, the intestinal cells told the same story.
Mice that received a transplant from a four-day-old pup showed intestinal cell damage and gut inflammation after they were infected with salmonella. These symptoms were absent in mice that had received a cecal transplant from an adult or adolescent donor. These recipients appeared to have healthy intestinal cells, even after infection with salmonella.
Next, the authors introduced symbiotic bacteria normally present in older mouse intestines into the transplant procedure. This meant that adult mice who received a transplant from a mouse pup would also receive these introduced bacteria. Remarkably, the modified transplants allowed the recipients to resist infection when they were exposed to new pathogens.
Some bacteria were more effective at helping mice resist infection than others: the naturally occurring gut bacteria Clostridia was notably best at helping mice resist new pathogens. Acquisition of Clostridia by young mouse pups may play a role in their ability to resist infections as they age.
In recent years, all manner of unexpected effects have been ascribed to the gut microbiome, leading some to call it the “second brain.” Partly in response, about a year ago, the Obama White House announced the initiation of a “Microbiome Initiative” to coordinate and fund microbiome research worldwide. If that initiative survives the change in administration, these new results may just be the first in a series of insights into the influence of intestinal inhabitants.
Science, 2017. DOI: 10.1126/science.aag2029 (About DOIs)