Research on the body’s microbiome is beginning to look at not just what is there, but how it works. Scientists have found a new way in which beneficial bacteria protect the gut.
In a study published in the journal Cell Reports, scientists at Emory University School of Medicine have shown how an ancient cellular regulatory circuit called Nrf2, present in both insects and mammals, responds to beneficial bacteria and gears up a protective response to environmental stresses.
“The body’s response to bacteria is often seen through the lens of the immune system,” says senior author Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. “The pathway we’ve identified is not inflammatory or immunoregulatory; rather, it’s cytoprotective.” Previous studies have looked at how these beneficial bacteria interact with the immune system, but this study found that the bacteria protected the lining of gut itself.
While many types of bacteria that live in our intestines are inert or even harmful to intestinal cells, a small subset – lactobacilli – can stimulate increased motility, proliferation and ability to withstand stress, Neish says.
“Lactobacilli are present in yogurt, and they’re also the first kind of bacteria that will colonize a baby’s system after the baby is born,” he says.
Working with Neish, assistant professor of pediatrics Rheinallt Jones, PhD and colleagues found that only lactobacilli could protect previously “germ free” fruit flies from paraquat, a toxic herbicide. Similarly, feeding lactobacilli, but not other types of bacteria, to germ-free mice could protect them from weight loss and death after exposure to radiation.
Looking at the intestinal tissues in both flies and mice, they saw that lactobacilli turned on a series of genes in a pattern that indicates that the Nrf2 pathway is involved. They found that lactobacilli did not help flies or the mice that had a mutation disabling Nrf2.
Nrf2 is a cellular pathway that protects cells against external stresses such as toxins and carcinogens, and reactive oxygen species (ROS) appears to activate the pathway.
“It looks like a little bit of ROS helps cells get ready to withstand stress,” Jones says. “This is an example of the concept of hormesis, where limited exposure to something that is harmful protects an organism from more of it later.”
While it is not the only regulatory circuit stimulated by beneficial bacteria, Jones and Neish say their findings suggest that Nrf2 is more highly conserved than other bacterially-induced signals, and that it likely evolved as a mechanism for higher organisms to co-exist with bacteria.
Jones and Neish say they are investigating the common genetic signatures of the various types of bacteria that stimulate ROS and Nrf2. That could help researchers sort through which ones may have therapeutic benefits, and possibly develop drugs that mimic the bacteria’s action.