A new study finds that gut bacteria play an important role in the development of white blood cells that help the body's immune system fight infection.
The human body is home to thousands of species of microbes - collectively known as the microbiome - that we are increasingly coming to realize are essential to health. The highest concentration and diversity of these species is found in the gastrointestinal tract, and the colon in particular.
With his team at the California Institute of Technology (Caltech) in Pasadena, Sarkis Mazmanian, a professor of biology and biological engineering, has been researching this area for some time.
Their work with mice has already led to numerous revelations about the importance of gut bacteria to health.
For example, in 2013, they reported a groundbreaking study that linked gut microbes to symptoms of autism, 3 years after they revealed how gut bacteria affect multiple sclerosis, and also how restoring their equilibrium may alleviate inflammatory bowel disease.
Gut bacteria instrumental to development of innate immune cells
In this latest study, published in the journal Cell Host & Microbe, they describe how they discovered that beneficial gut bacteria played a key role in the development of innate immune cells - specifically macrophages, monocytes and neutrophils - special white blood cells that provide a first line of defense against invading pathogens.
These white blood cells do not only circulate in the blood, they are also stored in the spleen and in bone marrow. When the team compared counts of white blood cells in these areas in mice born without gut bacteria - known as "germ-free" mice - and healthy mice with a normal gut bacteria population, they found the germ-free mice had fewer of them.
The germ-free mice also had fewer stemlike cells that can differentiate into some types of immune cells. Plus, their spleens contained defective innate immune cells whose populations never reached the size found in healthy mice with microbes in their gut.
Gut microbes influence immunity beyond the gut
First author Arya Khosravi, a graduate student in Prof. Mazmanian's lab, says:
"It's interesting to see that these microbes are having an immune effect beyond where they live in the gut. They're affecting places like your blood, spleen, and bone marrow - places where there shouldn't be any bacteria."
The team tested the mice's ability to fight off infection by exposing them to the bacterium Listeria monocytogenes, which is harmful to humans and often used in mouse studies of the immune system.
They found the healthy mice recovered quickly after being injected with the bacterium, but the germ-free mice died - they were not able to fight off the infection.
But when germ-free mice were then given gut bacteria typical of healthy mice, their white cell count increased, and they survived the infection.
And in another part of the study, the team gave healthy mice antibiotics to kill their gut bacteria and then injected them with Listeria. They got sick and had trouble fighting off the infection.
Could antibiotics kill off gut bacteria that protect us from other infections?
The researchers say these results prompt questions about infections in humans, as Prof. Mazmanian explains:
"For example, when patients are put on antibiotics for something like hip surgery, are you damaging their gut microbe population and making them more susceptible to an infection that had nothing to do with their hip surgery?"
And looking at it from the other side, could ensuring patients have healthy gut populations offer a preventive alternative to giving them antibiotics?
This opens a new avenue for dealing with superbugs that are resistant to antibiotics. Limiting susceptibility to infection might be a more fruitful strategy, the team suggests.