Gut bacteria influence social behavior through smell

• For Journalists
• News Releases
• Latest Releases
• News Release

Gut bacteria influence social behavior through smell

The microbiome produces scents that trigger aggression in mice

• Adult male mice use a foul-smelling odor produced by gut bacteria to signal to each other
• When other male mice smell the odor, it changes their behavior and shapes social hierarchies
• Researchers found the olfactory receptor that translates the scent into behavioral changes, such as aggression and dominance
• Study shows how the microbiome can influence behavior not just by affecting physiology, but also by driving social responses through smell

It takes two to start a fight: the gut microbiome and the nose, that is.

In a new study, Northwestern University neurobiologists discovered that gut bacteria and the nose work together to shape social behavior in mice, including who fights and who backs down.

Using a combination of genetic and behavioral experiments, the scientists found gut microbes produce a pungent odor that other animals can smell. When detected, these scents trigger aggression and shape social hierarchies. The discovery reveals a previously unknown way the microbiome influences social interactions.

Over time, these insights could inform research into animal behavior and, potentially, how microbe-produced odors might change perceptions and social responses in other species, including humans.

The study was published today (March 30) in the journal Current Biology.

"Over the past 20 years, there's been a growing realization that microbes in the gut have profound influences on behavior and physiology," said Northwestern's Thomas Bozza, who led the study. "They produce bioactive chemicals that affect the function of many organ systems including the immune system and can even cross the blood-brain barrier to affect behavior. These chemicals can also affect social behaviors through the sense of smell. While species use microbiome-derived chemicals for social communication, our study is the first to uncover the underlying mechanism."

An expert on olfactory-driven behaviors, Bozza is the Edgar C. Stuntz Distinguished Professor of Neurobiology at Northwestern's Weinberg College of Arts and Sciences.

A fishy molecule

In the new study, Bozza and his team focused on trimethylamine (TMA), a molecule produced in the gut that smells like dead, rotten fish. When gut bacteria break down choline-rich foods, such as eggs and meat, they generate TMA as a byproduct. The body's liver then converts TMA into an odorless metabolite. But in adult male mice, testosterone suppresses the liver enzyme that typically neutralizes TMA, allowing it to accumulate in urine.

"It seemed like mice use TMA as a male-specific odor," Bozza said. "But we weren't sure what they were doing with this odor. There was no social behavior tied to this chemical or its receptor."

To better understand why adult male mice produce this odor, Bozza's team imaged the olfactory bulb within the brain to see which neurons respond to TMA. They specifically focused on trace amine-associated receptors (TAARs), a small family of odor detectors that are especially sensitive to strong-smelling molecules. Among the 14 TAARs in mice, the team found that TAAR5 is the most sensitive receptor to TMA and plays a central role in detecting the odor.

From scent to social hierarchy

When mice detect this scent, it changes how they behave. Dominant animals initiate fights, while subordinate mice adopt defensive postures - patterns that quickly establish a social hierarchy. But when Bozza and his team disabled TAAR5 in mice, those distinctions blurred. Mice still interacted with one another, but their behavior became more evenly matched. Without this signal, it took longer for clear dominant-subordinate relationships to emerge.

"They end up establishing a hierarchy, but that hierarchy is less stable," Bozza said. "The animals don't recognize their place within the hierarchy and essentially miss social cues. That affects the dynamic among the animals."

After establishing that mice need the TAAR5 receptor to interpret the signal, the researchers next asked whether the odor, by itself, drives the behavior. To test this,

they manipulated TMA levels by going directly to the source - the gut. When the researchers blocked gut bacteria from producing TMA, aggression dropped. When they restored the chemical, aggressive behavior returned.

In another experiment, the researchers treated young mice, which typically do not exhibit aggression, with TMA. Adult mice responded by biting and fighting - treating the younger mice like rivals.

Implications beyond mice

Together, the findings map a complete pathway linking gut microbes to behavior through smell. Bacteria produce TMA, the nose detects it through TAAR5 and the signal helps determine social dominance.

"We can see, at least in this species, that the microbiome drives social behavior through a sensory system," Bozza said. "And this is the first case where we know the chemical, we know the receptor, and we know the neural pathways involved."

Bozza says the findings make him think differently about humans' sense of smell and how it relates to the microbiome.

"There are six intact TAARs in humans," he said. "The only one that we find reliably expressed in the olfactory system is TAAR5, which is the TMA receptor. While we probably don't use TAAR5 and TMA as an aggressive cue, we must have retained TAAR5 for a reason. It's a beautiful example of how the olfactory system has tuned itself to molecules produced by microbes with whom we share the environment."

The study, "A microbiome-derived olfactory signal regulates inter-male aggression and social dominance in mice," was supported by the National Institutes of Health.

Thomas Bozza

Corresponding author

Edgar C. Stuntz Distinguished Professor of Neurobiology

• [email protected]