The Critical Link Between the Microbiome, Motivation, and Cancer

Research is revealing how a virtuous cycle between exercise and a healthy microbiome may be a key cancer treatment

New studies offer insight into motivation and benefits of daily movement. TORWAISTUDIO/Shutterstock

Whether you’re searching for a simple way to improve your health, boost the effectiveness of your cancer treatment, or understand your complete lack of willpower when it comes to exercise, the answers could be found in your microbiome.

The gut microbiome is the ecological community of organisms called microbes—bacteria, viruses, and fungi—that live inside our intestinal tract.

A Virtuous Cycle

Two recent novel studies on exercise are pointing to similar conclusions—that the gut microbiome might be the reason we have trouble with fitness and that intentional daily movement increases beneficial bacteria that improve the microbiome.

One study found colorectal cancer patients who exercised even moderately gained more healthy, diverse microbiomes and improved their treatment outcomes.

Another study, conducted with mice, found that microbiome-dependent production of certain gut metabolites elevates dopamine levels during exercise and improves performance—thereby making it more rewarding.

The two findings suggest the possibility of a virtuous circle: exercise improves the microbiome, which increases motivation to exercise, which further enhances the microbiome.

A review study in Frontiers in Nutrition in 2021 further affirmed that cycle.

“Moderate endurance exercise reduces inflammation, improves body composition and leads to positive effects on gut microbial diversity and composition and its metabolic contribution to human health,” it found.

Deeper Insight

As microbiology research is gaining more precise knowledge and naming specific bacteria, the spotlight is shifting to etiology—the causes and origins of disease—and pathology, how the disease develops and progresses.

There are more than 100 trillion microbes that “influence human physiology, metabolism, nutrition, and immune function,” notes a 2013 study.

Our microbes help with all sorts of physiological functions such as turning food into energy and converting it into vitamins. Among their many roles, microbes break down toxins and fight off invading pathogenic bacteria and viruses. They’ve also been linked to our mental health.

Published in the American Journal of Cancer Research on Oct. 15, 2022, the cancer study is the first of its kind to look at how the gut microbiome can specifically affect cancer treatment outcomes, and it concluded that increased physical activity can prevent or counteract dysbiosis—an unhealthy microbial imbalance—due to obesity.

The study examining motivation in mice, published on Dec. 14, 2022, in Nature, is the first to connect a specific bacteria to a metabolic process linked to a region in the brain that controls exercise motivation.

Even those who have prioritized exercise for years describe days when they hit the gym only out of habit—not because they feel like it. The studies help clarify the mysterious physiological processes happening in the gut during exercise. They offer insight into behavior and outcomes that may help us tip the scale of motivation toward daily movement.

Cancer Study

Microbial communities, considered to be an “organ” in themselves, outnumber human cells 10 to one. They’re integral to overall health and could play a key part in reducing the cancer burden, as the new study illustrates.

“[W]e observed that alpha diversity was lower among ‘inactive’ patients and lowest among ‘overweight/obese/inactive.’ Alpha diversity describes the number of microbial species relative to its abundance within one sample and has been identified as an indicator of [a] healthy state with higher diversity indicating improved health,” reported the researchers in the cancer study.

Specifically, the more active patients had higher amounts of bacteria that protect against colorectal cancer, one of the study’s researchers, Caroline Himbert, who holds a doctorate in population health sciences said in a statement. A healthy microbiome is correlated to reduced inflammation, according to the study’s researchers, even in obese or overweight patients.

“Our study suggests that nobody needs to be an athlete to get the benefits. It can be easy activities,” she said. “Just staying active is very beneficial.”

Adults need 150 minutes of moderate exercise a week, according to the U.S. Centers for Disease Control and Prevention. That’s about 20 minutes of brisk walking or light jogging each day.

Another Cancer Connection

Not counting skin cancers, colorectal cancer is the third most common cancer in the United States, with 106,970 new cases of colon cancer and 44,050 new instances of rectal cancer this year, according to the American Cancer Society. Having high levels of inflammation, as seen in those with a higher body mass index or who aren’t physically active, increases a person’s risk of developing colon cancer.

Commensal and pathogenic bacteria are known to contribute to inflammation and cancer development. Inflammation is a normal protective mechanism the body undergoes when injured and infected, but chronic inflammation due to an imbalance of bacteria known as dysbiosis may linger for months or years, causing disease. Inflammation is believed to contribute to more than half of all deaths worldwide.

Experts have found that inflammation is necessary for tumor development, and increased pathogenic bacteria in a dysbiotic state leads to a pro-inflammatory response in the intestine and sometimes beyond. Dysbiosis can overamplify the immune response and break down the intestinal epithelial barrier.

Researchers are studying how the microbial ratios shift in cancer patients because preserving the integrity of the microbiome could prevent or slow down cancer development.

“Inflammation is a key process that drives colorectal cancer. We know a high BMI causes inflammation around the body,” said Cornelia Ulrich, who’s the executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute at the University of Utah.

“Obesity is on the verge of becoming the number one cause of cancer in the United States, surpassing smoking. More than 13 cancers are linked to obesity,” she added in the news release. “It’s important we understand that moderate exercise can help colorectal cancer patients reduce inflammation, improve their gut health, and live longer—even if they are overweight or obese.”

Mice Motivation Study

Knowing we need to exercise is one thing, but finding the desire to prioritize it can be a real struggle. The study in mice conducted at the University of Pennsylvania may have captured a collective sigh of relief among those who simply can’t find the energy to work out and don’t know why.

The researchers found differences in running performance within a large group of lab mice that were largely attributable to the presence of certain gut bacterial species in the higher-performing animals, according to a Penn Medicine statement. Those mice that ran endlessly on their wheels possessed bacteria that produce certain small molecules—called metabolites—that stimulate sensory nerves in the gut and communicate on a gut–brain axis to enhance activity in a motivation-controlling brain region during exercise.

“If we can confirm the presence of a similar pathway in humans, it could offer an effective way to boost people’s levels of exercise to improve public health generally,” study senior author Christoph Thaiss said, whose doctoral research focused on the role of the intestinal microbiome in metabolic and inflammatory diseases.

Thaiss and colleagues recorded the genome sequences, gut bacterial species, bloodstream metabolites, and other data for genetically diverse mice. They then measured the amount of daily voluntary wheel running the animals did, as well as their endurance, searching broadly for factors that determine exercise performance.

Results showed that genetics seemed to account for only a small portion of performance differences, but differences in gut bacterial populations played a much larger role. They gave mice broad-spectrum antibiotics to get rid of their gut bacteria, and it reduced the mice’s running performance by about half.

Years of detective work have allowed researchers to conclude that two bacterial species are closely tied to better performance: Eubacterium rectale and Coprococcus eutactus, which produce metabolites known as fatty acid amides. These fatty acid amides stimulate receptors on gut-embedded sensory nerves that travel to the brain from the spine and cause an increase in the neurotransmitter dopamine during exercise.

Dopamine is released from a brain region called the ventral striatum, a critical node in the brain’s reward and motivation network. The researchers concluded that extra dopamine in this region during exercise boosts performance because it reinforces the desire to exercise.

It’s the first time the microbiome has been connected to what’s referred to as a “runner’s high”—when a state of euphoria is experienced during intense exercise. This gut-brain axis is an area of study that researchers said could develop into a branch of exercise physiology.

But first, the team must confirm the existence of this gut-to-brain pathway in humans, where it could play a part in understanding other conditions, such as depression and addiction, that are impacted by motivation.

Practical Takeaways

Cancer diagnosis or not, people who care about their health can assume exercise is the right prescription for them. Plenty of other research has connected exercise to certain cancer survival rates and longevity in general.

A couple of decades ago, exercise wasn’t recommended for cancer patients. But that advice has changed.

“We are at a point in the evolution of the field where we can dose exercise precisely, just as we do with drugs, to address several cancer-related health outcomes,” said Kathryn Schmitz, professor at the University of Pittsburgh Department of Medicine’s division of hematology/oncology. She led a panel that helped rewrite guidelines for cancer prevention and survivorship.

“We need a paradigm shift here, as we have had with exercise and heart disease.”

In a 2019 National Cancer Institute article, Schmitz wrote that providers rarely discuss exercise with cancer patients, in part due to lack of time. Another reason they don’t bring up the subject is that they feel uncertain about whether it’s safe for certain patients, and they feel unsure about specific advice.

But the research is clear—exercise leads to better health. There’s evidence that 30 minutes of aerobic exercise three times a week can improve anxiety, depression, fatigue, quality of life, and physical function in cancer survivors.

“The ACSM’s [American College of Sports Medicine’s] recommendation to providers is simple,“ Schmitz wrote. ”Ask cancer patients about their physical activity. If their activity is inadequate, providers should advise their patients to do more.”