(ORDO NEWS) — Since there are more microbes in our body than cells, it is not surprising that bacteria and other invisible “guests” affect our metabolism, immune system, and even our behavior.
Now, researchers studying mice have figured out how bacteria in the mammalian gut can send signals to the brain to regulate the animal’s appetite and body temperature, and this happens along the same molecular pathway that the immune system uses to detect bacterial pathogens.
“This is quite an important discovery,” says Antoine Adamantidis, a neuroscientist at the University of Bern who was not involved in the work. “Our life depends on the consumption of food, and this is another [thing] that bacteria can [affect].”
Over the past 20 years, researchers have discovered links between the human gut and the rest of the body. They have linked certain gut microbes to diseases such as depression, multiple sclerosis, and immune system disorders; they also documented the connections of the nervous system between the gut and the brain. However, researchers have not yet been able to understand exactly how gut microbes – or the molecules they produce – affect the brain.
When certain gut bacteria invade the rest of the body, our immune system detects them by picking up fragments of their cell walls, known as muropeptides.
Our molecular detectors of these muropeptides, proteins called Nod2, coat the surfaces of cells involved in the body’s first line of defense. Ilana Gabanyi, a neuroimmunologist at the Pasteur Institute, wanted to know if these molecular detectors also exist in nerve cells in the brain.
Gabagni and his colleagues started with genetically engineered mice: Some were engineered to lack Nod2, while others were engineered to produce a fluorescent label that marked where the molecular detector had been placed.
The first evidence that muropeptides affect appetite came from mice lacking Nod2. Compared to normal mice, these rodents gained extra weight with age.
This suggests that the muropeptides may provide a “full” signal to the brain, which is absent in mice lacking Nod2, Gabagni says. Because food can stimulate microbes in the gut, eating likely triggers the release of muropeptides, she adds.
She and her colleagues then fed some radioactive muropeptides to other mice. Four hours later, they checked where the muropeptides traveled in the rodents. By monitoring the radioactivity, they found that the muropeptides had entered the brain.
Together, these experiments showed that Nod2 is indeed produced in the mouse brain, and that muropeptides can get there within hours of entering the gut, Gabanyi and colleagues report today in the journal Science.
“I had no idea these [fragments] were going to the brain,” says Christine McDonald, a molecular biologist who studies the body’s bacterial sensors at the Cleveland Clinic.
The experiments also showed that radioactive muropeptides accumulate in the brains of female mice to a greater extent than in the brains of males, and have a stronger effect on females, says Gabagni.
Elderly female mice lacking Nod2 in their brains ate more per meal than mice not genetically modified. They also maintained a higher body temperature and spent less time building nests to keep warm, indicating that Nod2 may play other physiological roles as well.
Disruption of this gut-brain communication pathway had other downsides: Female mice without normal Nod2 levels are prone to developing diabetes and do not live as long as normal mice.
Mice given antibiotics to kill gut bacteria experienced similar problems; the researchers believe this is because the muropeptides weren’t getting to the brain to help regulate appetite and body temperature.
According to Livia Hecke Morais, a neuroscientist at the California Institute of Technology, the new experiments have revealed a direct mechanism by which bacteria can control the brain. So far, there has been “no evidence of such direct links,” adds Margaret McFall-Ngay, a developmental biologist at the Carnegie Institute of Science.
It is not clear which came first: the role of Nod2 in the brain or its immune function. “The same molecule that alerts our immune system that something is wrong can be used by our nervous system as a signal to regulate key survival processes” such as food intake and temperature control, says Juan Escobar, an evolutionary biologist. studying gut microbes at the Vidarium Research Center for Nutrition, Health and Wellness, who was not involved in the work.
Based on their findings in aged female mice, Gabagni and her colleagues suggest that the muropeptide control system becomes increasingly important as the hormonal regulation of appetite and body temperature declines with age.
Similar hormonal changes in women entering menopause are associated with weight gain and hot flashes, so researchers are wondering if the muropeptide-Nod2 system could be a non-hormonal target for treating these problems. If this system exists in humans, then “the potential [for treatment] is very high,” says Morais.
Other scientists emphasize that the results of the study were obtained on mice and therefore require further study.
But McFall-Ngai notes that in squid, Nod2 also picks up fragments of the bacterial cell wall and helps control the development of the animal. Therefore, she is convinced that this communication system is ancient and probably found in all vertebrates.
—
Online:
Contact us: [email protected]
Our Standards, Terms of Use: Standard Terms And Conditions.