Microbes may be helping stir up anxiety and depression in obese people, if results from a new mouse study hold true in humans. 

The authors link the effects to how the brain responds to insulin, the hormone that regulates sugar levels in the blood. 

The research raises questions about whether changing gut microbes, or changing diet, could help treat these conditions. 

Mood, microbes and metabolism

Obesity triggers changes in metabolism — for example, making liver, muscle, fat and other tissues less responsive to insulin. Left untreated, these changes can lead to diabetes. 

Obese people also have higher rates of anxiety and depression. 

“One could say, ‘Maybe that’s just because they’re obese,’ ” said Harvard Medical School diabetes researcher Ronald Kahn, “but others could say, ‘Maybe there’s a metabolic link.’ ”

“And we asked the question, ‘Maybe the metabolic link is at least partly fueled by the microbiome,’ ” the community of microbes living in a person’s gut, he added.

Those microbes change with diet, and Kahn said different microbes might respond differently to the foods we eat.

To test the theory, Kahn and colleagues fed mice a high-fat diet and studied their behavior as the animals became obese. 

They used common tests to gauge anxious and depressed behavior in rodents — for example, how much time the animals spent hiding in a dark box versus exploring a brightly lit area. The more anxious the mouse, the less time it will spend in the light.

Obese mice spent about 25 percent less time in the light than animals on a normal diet, and they scored higher on the other anxiety and depression tests, too.

Return to normal

But those differences disappeared when obese mice were given antibiotics, even though their weight didn’t change much.

“That really says there’s probably something about the microbiome,” Kahn said. 

The researchers then tested how the animals’ microbiomes affected mice raised in a sterile environment with no microbes of their own. 

Bacteria from obese rodents made these germ-free mice more anxious than microbes from normal mice.

But when germ-free mice got microbes from obese animals that had been given antibiotics, they behaved like normal mice. 

To see what parts of the brain might be responsible for the effects, the researchers focused on two regions involved in metabolism and responses to rewards. They found these regions were less responsive to insulin in the obese mice compared with normal-weight animals. 

Again, antibiotics returned those responses to normal. 

The research appears in the journal Molecular Psychiatry. 

“It was actually quite a surprise,” Kahn said. “Even though we had seen some effects on metabolism in the rest of the body, I was very surprised how dramatic and how clear the effects were also on the brain and on behavior.”

Into the unknown

That doesn’t mean antibiotics are the cure for obesity, Kahn warned. The drugs kill good and bad microbes indiscriminately, and taking the medication unnecessarily can contribute to the rising threat of antibiotic resistance. 

Also, what happens in mice does not necessarily happen in humans, he added, or it may happen for only some people. So far, there is not much evidence that probiotics help anxious people. 

“The difficulty is, both of these things — depression and obesity — are complicated things that have multiple, multiple factors influencing them,” said mental health researcher Gregory Simon at Kaiser Permanente Washington Health Research Institute, who was not part of the study.

Microbes are likely just one factor, along with environment, genetics, social influences and more, Simon added.

But Kahn said his group’s research raised interesting questions about how food affects our behavior. 

“I think now we can get some idea that there are a lot of things that are being metabolized by gut bacteria that could affect brain function,” he said.

And he said there might be ways to change brain function by changing those bacteria, by eating helpful microbes or by eating foods that sustain them. 

He and his colleagues are working to figure out exactly which of the hundreds of species of gut bacteria are responsible. At the moment, it’s a mystery. 
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