GUT BACTERIA, BRAIN HEALTH AND OBESITY

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The Next Frontier of Medicine

Following your gut takes on a whole new meaning as scientists find relationships between the brain and gut bacteria. 

By Mitch Moxley

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The next frontier of medicine isn’t in the depths of an Amazon jungle or in an air-conditioned lab; it’s in the rich and mysterious bacterial swamp of your gut. Long viewed as an enemy within, bacteria in the body have been subjected to a century-long war in which antibiotics have been the medical weapon of choice. But today, the scientific consensus about our body’s relationship with the trillions of microbes that call it home—collectively known as the microbiome—is changing dramatically. From potentially shaping our personalities to fighting obesity, the bacteria in our bellies play a much stronger role in our overall health than we once thought.

Developments in sequencing technology in the last decade have allowed scientists to better understand gut bacteria, and recent studies have shed light on how our digestive systems may mold brain structure when we’re young and influence our moods, feelings, and behavior when we’re adults. Scientists experimenting on mice have found links between gut bacteria and conditions similar to autism and anxiety in humans.

While it’s still early, the implications of better understanding how gut bacteria impacts our minds and bodies could change the way doctors treat myriad conditions, says Michael A. Fischbach, a microbiologist at UC San Francisco (UCSF). “If we use history as a guide, a lot of ideas probably won’t work out,” Fischbach says. “But even if one of them does, it’s a huge deal.”

In 2012, Fischbach wrote an article in the journal Science Translational Medicine that served as an overview of medical ecology, the term used to describe the new field of study. Not long before, Fischbach had been studying drugs developed from microorganisms, trying to determine what characteristics the drug-encoding genes shared. During his research, Fischbach noticed that the most interesting drug-encoding genes were found in the human microbiome—including gut bacteria. “It was a big surprise. It’s just not where people turn to when looking for new drugs. It was sort of an ‘a-ha’ moment,” he recalls.

Fischbach switched from studying exotic soil bacteria to human bacteria and has since become a champion of the field. He runs a lab at UCSF that focuses on studying natural products—small molecules from microbes—that are used as antibiotics, anticancer agents, immunosuppressants, and cholesterol-lowering drugs. Among other things, Fischbach and his team are mining gut- and skin-associated bacteria for natural products that play crucial roles in human physiology and disease, and are examining the relationship between gut bacteria and diseases such as Crohn’s disease and obesity.

UCSF Microbiologist Michael A. Fischbach.

Photo by Cindy Chew

The study of gut bacteria reaches numerous fields of medicine. New studies suggest that by better tending to the bacteria in our guts—which help digest food and make vitamins and amino acids—doctors may be able to fight infectious diseases with less harmful side effects, as well as possibly treat diabetes, obesity, and more.

One prominent experiment found that it might be possible to change the bacteria in an obese person’s gut to help a person slim down. In the experiment, researchers found pairs of human twins in which one was obese and the other lean. They placed gut bacteria from these twins into mice and found that, coupled with a low-fat diet, bacteria from a lean twin took over the gut of a mouse that already had bacteria from a fat twin, prompting the mouse to lose weight. Regardless of diet, bacteria from a fat mouse did not take over in a mouse that is thin.

Fischbach notes that when considering obesity, diet is crucial—in January 2014, Fischbach co-authored a paper in the journal Nature that demonstrated how diet influences the human gut microbiome—but it’s not everything. Microbes digest food, and “the idea is that there are some kinds of bacteria that harvest more or less energy that others. Some leave fewer calories for you,” he says.

These new findings are also fundamentally changing our understanding of the immune system. Scientists long believed our immune systems only had to distinguish between human and non-human cells and viruses. In fact, Fischbach says, it also has to distinguish between harmful and helpful bacteria. “It engages in productive interactions with helpful bacteria,” he says. “It was a paradigm shift in immunology.”

A shift is also underway in our understanding of how the gut bacteria interact with our minds. New research is looking at the brains of thousands of volunteers and comparing their brain structure to the types of bacteria in their guts. The findings suggest that the connections between brain regions differed depending on which species of bacteria were prevalent in a person’s gut.

In one study, scientists examined gut microbes in mice and found that by swapping bacteria of anxious mice with that of fearless mice, the mice became less timid. The opposite worked, as well: bold mice became more nervous when their bacteria were swapped. The scientists measured the brain chemistry in the mice and found changes in the part of the brain governing emotion and mood.

Scientists might be able to give people good bacteria—called probiotics—to prevent or treat conditions such as autism. One team of scientists has tested mice that exhibit behaviors similar to the symptoms of autism in humans, in order to gauge whether probiotics might correct problems in the animals’ gastrointestinal systems. The mice’s autistic behaviors were diminished after being administered probiotics.

“That tells us that [gut bacteria] is part of the story,” Fischbach says. “The experiment doesn’t prove that gut bacteria cause autism. What it does do—and this is important—is it builds the plausibility case. That didn’t exist before.”

Tests on humans, however, are only beginning. One team is testing a probiotic to see if it can help treat relapses of mania among patients suffering from bipolar disorder (those findings have yet to be released). In a separate study, researchers gave healthy women yogurt containing probiotics and then scanned their brains. There were subtle signs that the brain circuits involved in anxiety were less reactive.

Fischbach believes scientists are just at the tip of the iceberg when it comes to understanding the microbiome. “I express my enthusiasm and excitement, while at the same time it’s still very early days” Fischbach says. “We’ve been ignoring a major player in the equation for a long, long time.”