New research published in Molecular Psychiatry holds some sobering news for anyone excited about trying a high-fat keto diet. According to the paper, released Monday, a high-fat diet might do more than change the way a body looks on the outside: It can fundamentally change the colony of bacteria that lives in the gut, which, in turn, can affect behavior.

The team behind the paper, led by Dr. C. Ronald Kahn, a professor at Harvard Medical School, wanted to investigate the connection between obesity, diabetes, anxiety, and depression, which commonly occur together. A small but growing body of research has suggested that mental health is strongly influenced by the bacteria of the gut, so Kahn and his team studied the gut bacteria of mice on obesity-inducing diets and observed their behavior.

“It turns out when you put mice on a high-fat diet they show a lot of behaviors that reflect more and anxiety and more depressive like behaviors,’ Kahn tells Inverse.

Kahn’s research suggests that the unlikely connection between physical health and mental health lies in 10 to 100 trillion bacteria that co-exist in the digestive tract to help us digest our food. These bacteria — also called the microbiome — come from a variety of different sources; some are there from birth, some develop over time, and others are consumed with food. By helping break down food, explains Kahn, who is also co-head of integrative physiology and metabolism at Joslin Diabetes Center, the bacteria aid in the production of certain metabolites — compounds like hormones or even neurotransmitters — that the brain uses as messengers between cells. And messing with the brain’s ability to signal can cause a whole bunch of other processes to go awry.

microbiome anxiety depression
The Google search activity for "Microbiome' since 2004. More and more people are becoming captivated by the microbiome--which research has shown can have effects on brain activity and mood. 

“In doing this [the bacteria] help certain metabolites enter the bloodstream that might not otherwise enter the bloodstream,” he adds. “And so we measured blood metabolites and even brain metabolites in these mice, and we showed that when you change to a high fat diet, a number of metabolites in the blood and the brain change.”

In the experiments, a group of mice were fed a high-fat diet — one where 60 percent of calories came from fat. They evaluated these mice for certain anxiety and depressive-like behaviors using established experiments like the light-dark exploration model, in which mice that choose to hang out in a dark rather than light room are deemed more anxious.

They also measured the levels of 116 metabolites, discovering a two-fold increase in the signaling of a protein in the brain called BDNF among the mice that ate fatty foods. Other studies have linked increased BDNF signaling and risk factors for depression, like “social defeat.”

microbiome anxiety mice experiment
One way that researchers measure anxiety in mice is to put them into a box with a dark and light section. In this study, the anxious mice on a high-fat diet hung out in the darker section. 

In the next part of the experiment, they put some of those high-fat mice on a series of antibiotics intended to kill off certain bacteria to determine how manipulating the microbiome might change certain behaviors. When they did this, they found that the depressive behaviors were reversed, and the metabolite levels changed correspondingly. The same likely holds true for humans, though that will have to be addressed in follow-up studies.

As we learn more about the mind-gut connection in humans, Kahn is adamant that antibiotics will not be the answer to regulating mood disorders. Nor does his research show that short-term shifts in mood — think: a post-sugar-binge energy crash — has anything to do with the microbiome. Instead, his research shows that changing your diet — in particular high-fat diets — can have real effects on how your body functions from your gut all the way up to your brain.

In addition to making dramatic diet changes, he says, there are ways you might be able to manipulate your microbiome to improve certain metabolite levels.

“In the meantime,” says Kahn, “I think people can think about changing their diets to increase bacteria and metabolites through normal diet changes or by taking probiotics or pre-biotics — something that’s very safe to do.”


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