Your digestive system plays host to a mind-boggling 100 trillion microbes — microscopic pinch-hitters that allow you to absorb energy from your food and churn out compounds like serotonin, which affect your mental well-being. While some of these microbes take up residence in your gut from birth, others emerge or wane depending on the lifestyle choices you make.
New research suggests that if you exercise, take antidepressants or use cannabis, your gut-bacterial balance may shift profoundly. But scientists still face a so-called black box conundrum: They’re not always sure what biological processes cause these microbial shifts or how the shifts affect other body functions. Planned larger-scale studies promise to deepen experts’ understanding of the bacterial changes your daily habits usher in, as well as the long-term health implications.
Exercise to Colonize
Not only does regular exercise boost your overall well-being, it also swells the ranks of gut bacteria that promote a healthy metabolism, says Satu Pekkala, a bacteriologist at Finland’s University of Jyväskylä.
In a 2018 study, Pekkala and his colleagues recruited 17 overweight women who participated in three endurance exercise sessions each week for six weeks. The women rode an exercise bike that adjusted workout intensity so that riders stayed at about 85% of their maximum heart rate.
The team had participants collect stool samples before and after the six-week training period, then sequenced DNA from these samples to detect changes in the women’s gut bacteria. After the training regimen, the women had higher levels of gut bacteria from the genus Akkermansia — a bacterial group tied to improved metabolic function — than they had before. They also had lower levels of Proteobacteria, a genus linked to inflammation in the body.
Pekkala has secured approval to conduct another study that examines bacteria-produced molecules to explore what biological role Akkermansia and Proteobacteria might play in the gut — and how Akkermansia abundance might affect the body’s ability to burn fat stores. “Not everybody loses fat mass even if they exercise,” Pekkala says. “It’s important to know how the metabolic functions [of gut bacteria] affect fat loss.”
The Cannabis Connection
Plenty of research shows that marijuana compounds reduce disease-related inflammation, and, according to a 2019 study, these compounds’ effects on gut bacteria might explain some of their anti-inflammatory properties.
In exploring possible treatments for Multiple Sclerosis (MS), University of South Carolina researchers treated mice that had a similar condition with molecules like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
The mice showed fewer signs of inflammation after the cannabis treatment — and an analysis showed that gut-bacterial shifts were likely responsible, at least in part. Before treatment, the mice had high levels of the bacterial species Akkermansia muciniphila, which produces compounds called lipopolysaccharides that are linked to brain inflammation. After treatment, mice had lower levels of this species in their guts and lower levels of lipopolysaccharides in their brains. Future studies may show whether cannabis can spur similar gut-bacterial and brain changes in humans with MS.
An antidepressant that millions of Americans take may alter their gut-bacterial mix as well as their mental outlook, University of California-Los Angeles researchers say. In a 2019 study, the UCLA team added fluoxetine (Prozac) to a tube with a common gut bacterial species called Turicibacter sanguinis, which normally tells intestinal cells to produce more serotonin — a neurotransmitter that affects mood. After the team put in fluoxetine, the bacteria transported less serotonin than it had before. Further experiments showed that mice dosed with fluoxetine had lower gut levels of Turicibacter than other mice.
These results suggest that Turicibacter populations fluctuate in the presence of drugs like fluoxetine that modify serotonin levels. Next, the UCLA team plans to tease out the molecular mechanisms that reveal just how fluoxetine affects certain gut bacteria — and how that might influence the way the drug works in the brain and the rest of the body. “There’s variation in how effective fluoxetine is for different people,” says UCLA microbiologist Jonathan Lynch. “Something like the interaction with the microbiome might be mediating that.”
Future studies of these gut-brain interactions could allow a personalized-medicine approach that identifies people who are good candidates to respond to drugs like fluoxetine, Lynch says. Someday, based on your gut microbe profile, doctors might be able to tell you which antidepressants will work for you and which ones you shouldn’t even try.