Think about what you ate for lunch today. Did it feel like something you wanted, something you chose? Or was it something that the Lactobacilli in your digestive tract was actually jonesing for? A new study in fruit flies suggests that the latter idea might not be so outlandish.
To a fruit fly, yeast is like a big, juicy steak. The microscopic fungus provides protein and, during mating, a fly's brain circuitry can be altered to make them crave it. So when neuroscientist Carlos Ribeiro noticed that some of his flies were passing it over—even when he starved them of protein—he took note. Fruit flies deprived of protein usually gorge themselves on yeast. He decided to take a closer look. "That launched us into this completely unexpected direction," he says.
Ribeiro and his colleagues at the Champalimaud Centre for the Unknown (CCU) in Lisbon, Portugal, study how the brain decides what animals choose to eat, and when. In his flies, he found that their eating decisions were not being made in the brain at all, but by their stomachs and the bacteria that live there. His results, published today in PLOS Biology, offer the latest evidence that the microbes living in our guts have more influence on our food choices than we'd like to think.
Ribeiro's team at CCU, in collaboration with a colleague from Monash University in Australia, discovered that it was flies that carried Acetobacter pomorum and Lactobacilli who turned their noses up at the yeast.
He fed flies a diet lacking in essential amino acids, which is known to cause an increase in yeast appetite and fertility problems. Bacteria-free flies ate more yeast, as expected, and produced fewer eggs. But flies with Acetobacter pomorum and Lactobacilli didn't develop an appetite for extra protein and were protected from fertility problems—they continued to eat and reproduce normally, as if they were not deficient. "The bacteria literally reprogrammed the body's nutritional needs," the center said in a press release.
Ribeiro first thought that the bacteria were producing amino acids, and replacing what was lost. But after measuring the amount of amino acids in flies with and without bacteria, he found that wasn't the case. "There seems to be a new way by which bacteria interact with the brain to change these specific appetites," Ribeiro says. "And that's obviously really intriguing how they do that."
Ribeiro says he can't say whether his study proves that people also have gut bacteria that directly change what we crave and eat. His fruit flies only had five major gut bacteria, so it was easier to narrow it down to the two driving the food decisions. In humans—a much more complicated species than the fly—the microbiome is also much, much larger and more diverse.
But it is becoming clear that the connection between the stomach and the brain is worth examining, especially in humans. Your gut and brain are constantly communicating using hormones, neurotransmitters and other chemicals. The stomach is referred to as the "second brain" or "mini-brain" because it contains hundreds of millions of neurons that make up the enteric nervous system, just as many neurons as in the spinal cord. There is a growing body of research indicating that the 100 trillion bacteria that live in the gut might take advantage of these connections and use it to influence their hosts.
A 2015 paper in Cell Metabolism found that 20 minutes after a meal, gut microbes in mice produced proteins that told the brain it was full. Injecting the same protein into mice and rats could reduce appetite, even when the animal hadn't eaten. It suggests that our gut, and gut bacteria, have a say in whether we feel full, or continue snacking.
Joe Alcock, a biologist and associate professor at the University of New Mexico, thinks that our struggles with eating foods high in sugar and fat can partly be explained by the survival needs of our microbiomes, and argued so in a 2014 paper in BioEssays. There are certain bacteria that thrive on specific kinds of food, Alcock says. Bacteria could be making the foods they want seem tastier to us, by changing taste receptors.
Ribeiro thinks that his new work has found a symbiotic relationship between gut flora and the fruit fly: that the change in appetite caused by the bacteria is helping the fly survive. Alcock, meanwhile, isn't sure that our commensal bacteria (or that of the flies) have our best interests at heart.
"That's the real crux of the matter, is interpreting exactly what's going on and trying to figure out who is benefitting," Alcock says. "I don't think that they've made the case that this is good for the fruit fly, or that it's adaptive. But you can definitely argue that the results they show are indeed a manipulation of the host behavior by the microbes."
Emeran Mayer, a professor at the David Geffen School of Medicine at UCLA and the author of The Mind-Gut Connection, warns that a human brain is much more complex than a fly's, and that should be considered before we start to believe we're under mind-control by our microbiomes. But Mayer has done a study in humans that suggests similar results. In a paper just accepted but not yet published, he looked at patients before and after bariatric surgery, which is known to cause changes in the microbiota.
In a sample size of eight obese women, Mayer found that one month after surgery, their cravings for high fat and sugar went substantially down, though the preference for protein stayed the same. He also found that their microbes had changed, as did the metabolites, or small molecules, that the microbes produce.
"I think this new study continues to support the idea that certain microbes produce metabolites that affect the brain and feeding behavior," he says, adding, "I'm going to look at the strains of species we identified that changed with the weight-loss surgery. If they're related in any way to those two organisms that this PLOS paper showed, that would be amazing."
For Mayer, the gut-brain-microbiome triad offers a new lens to look at all sorts of diseases, not just diet or obesity. Beyond food, the microbiome has been implicated in other human brain diseases, like autism spectrum disorder, anxiety, depression, or chronic pain. For example, intriguing studies show that moving the microbiota of anxious mice to germ-free, non-anxious mice could increase their anxiety levels, and the reverse was true as well.
All future research will require the ability to accept that at some level, we are not individuals, but a collection of organisms with various, and possibly competing, needs.
"We need to accept that we are not only 'us' but also the microbes we have in our gut," Ribeiro says. "We want to have a holistic understanding of how animals and humans behave, we have to tackle that at the level of the whole organism. Now the organism is multi-dimensional. We are more than just ourselves, but also these microbes are a part of us."
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