The connection between gut microbiota and obesity that recent research has revealed is exciting, but obesity is perhaps only the tip of the iceberg of physical and mental conditions that gut microbiota influence. Dr. Laura C. Bridgewater, professor of Microbiology and Molecular Biology in BYU’s College of Life Sciences and a presenter at our recent gerontology conference, explained that the microbes and bacteria that live in our guts have also been shown to be connected to anxiety.

From Bold to Timid

“There’s good evidence in mice that gut bacteria can directly impact anxiety,” Bridgewater said. Researchers who swapped gut microbiota between bold mice and timid mice found that, over time, their personalities changed. They put mice on a platform and timed how long it took them to get down. After the gut microbiota transfer, the bold mice became more afraid and took longer to get down, while the timid mice got down much faster.

During a sabbatical at Shanghai Jiao Tong University, Dr. Bridgewater worked with Professor Liping Zhao, a leading researcher in gut microbiota. “His lab had worked on gut microbiota, obesity, heart disease and metabolic syndrome,” said Bridgewater. “They hadn’t done any behavioral studies before…so when I came, we started working on this question [of gut microbiota and its link to anxiety] and we got some pretty interesting results.”

Bridgewater and her colleagues were interested in seeing the effects of diet, stress and gender. They tested these effects on mice. The research lasted for 136 days. At specific checkpoints throughout that time, the researchers tested for three things:

• the composition of the gut microbiota
• anxiety levels
• overall activity

The latter two were measured through behavioral testing. The testing for
anxiety included an open field test and an elevated plus maze, like the one above.

Movements of the mice were digitally tracked and analyzed. More anxiety was reflected by increased time spent in the walled arms of the maze and on the outer edges of the open field test (not in the open arms and exposed middle). This was determined because when mice were given anti-anxiety drugs, they spent more time in the dangerous areas of the maze and in the middle of the open field test.

Does Diet or Gender Have Anything to do With It?

At day zero, initial testing was done and recorded. Afterwards, the mice were placed on two different diets. Half of the mice were put on a high fat diet (60% fat), while the other half ate a normal chow diet. Testing was completed again at day 81. The researchers made an interesting observation at this point:

The high fat diet increased anxiety in males, but not in females. The diet seemed to have very little impact or no impact on the female’s anxiety levels.

The researchers then added the variable of stress. The mice were exposed to chronic unpredictable mild stress every day for two and a half weeks. This included things like predator sounds, damp bedding, lights on all night, lights off all day, etc. After another round of behavioral testing, the researchers observed that:

After the stress, the females showed a lot more anxiety, but the male’s patterns hadn’t changed much from the previous round of testing.

The researchers also found that male activity levels only decreased from the high fat diet, not the stress, whereas females decreased activity based on the stress, not the diet.

Impact on the Gut Microbiota

They also found that diet made the biggest difference in the gut microbiota. Seeing as it affected the behavior of each gender differently, Bridgewater observed, “There is something inherently different about males and females that are on the same diet and experiencing the same thing.”

After stress, the composition of the female gut microbiota looked more like the mice that had been on the high fat diet all along. At day zero, the gut microbiota of all the female mice were very similar. By day 81, there was a dramatic difference between gut microbiota of mice on the normal chow diet compared to the high fat diet.  On day 136, after the stress, the difference between the groups decreased and they began to resemble each other again. “You don’t see that in the male group after the stress. Their gut microbiota didn’t change very much after the stress,” Bridgewater said.

The researchers came away with this understanding: when it comes to increased anxiety, females seem to be more vulnerable to the stress, but resistant to the high fat diet. The males are just the opposite.

The Biology Behind It

When you look at the biology behind it, the connection isn’t actually that surprising, Bridgewater explained. A few studies have shown that gut bacteria can influence the brain by producing neurotransmitters such as GABA, norepinephrine, serotonin, and dopamine. In addition, the vagus nerve, the longest nerve in the human body, connects the brain to the digestive tract.

The implications of the findings made by Doctors Bridgewater and Zhao, as well as other corroborative studies are exciting, as other researchers begin to investigate the connection in humans and the effect of pre- and pro-biotics.

 

All images courtesy of Pixabay.