Introducing this bacteria to sedentary individuals improves exercise capacity
BOSTON – (June 24, 2019) — New research has identified a type of bacteria found in the microbiomes of elite athletes that contributes to improved capacity for exercise. These bacteria, members of the genus Veillonella, are not found in the guts of sedentary people.
By taking a closer look at the bacteria, the researchers from Joslin Diabetes Center determined Veillonella
metabolizes lactic acid produced by exercise and converts it into
propionate, a short chain fatty acid. The human body then utilizes that
propionate to improve exercise capacity. The results were reported
today in Nature Medicine.
“Having increased exercise
capacity is a strong predictor of overall health and protection against
cardiovascular disease, diabetes, and overall longevity,” says
Aleksandar D. Kostic PhD, Assistant Investigator in the Section on
Pathophysiology and Molecular Pharmacology and a co-author on the paper.
“What we envision is a probiotic supplement that people can take that
will increase their ability to do meaningful exercise and therefore
protect them against chronic diseases including diabetes.”
The work began in 2015 with fecal samples from Boston Marathon runners. Jonathan Scheiman, PhD, then a researcher in the lab of George Church, PhD, at Harvard Medical School, collected samples during a time span of one week before the Marathon to one week after the Marathon. He also collected samples from sedentary individuals. Dr. Scheiman then brought the samples to Dr. Kostic, who analyzed them to determine the species of bacteria in both cohorts.
“One of the things that immediately caught our attention was this single organism, Veillonella, that was clearly enriched in abundance immediately after the marathon in the runners. Veillonella is also at higher abundance in the marathon runners [in general] than it is in sedentary individuals.” says Dr. Kostic.
They
confirmed the link to improved exercise capacity in mouse models, where
they saw a marked increase in running ability after supplementation
with Veillonella. Next, they wanted to figure out how it worked.
“As we dug into the details of Veillonella,
what we found was that it is relatively unique in the human microbiome
in that it uses lactate or lactic acid as its sole carbon source,” he
says.
Lactic acid is produced by the muscles during strenuous exercise. The Veillonella bacteria are able to use this exercise by-product as their main food source.
“Our
immediate hypothesis was that it worked as a metabolic sink to remove
lactate from the system, the idea being that lactate build-up in the
muscles creates fatigue,” he says. “But talking to people like Sarah
Lessard, [a clinical researcher at Joslin] and other people in the
exercise physiology field, apparently this idea that lactate build-up
causes fatigue is not accepted to be true. So, it caused us to rethink
the mechanism of how this is happening.”
Dr. Kostic and his team
returned to the lab to figure out what could be causing the increase in
exercise capacity. They ran a metagenomic analysis, meaning they tracked
the genetics of all the organisms in the microbiome community, to
determine what events were triggered by Veillonella’s
metabolism of lactic acid. They noted that the enzymes associated with
conversion of lactic acid into the short chain fatty acid propionate
were at much higher abundance after exercise.
“Then the question
was maybe it’s not removal of lactic acid, but the generation of
propionate,” says Dr. Kostic. “We did some experiments to introduce
propionate into mice [via enema] and test whether that was sufficient
for this increased running ability phenotype. And it was.”
Dr.
Kostic and his team plan to investigate the mechanisms of how propionate
affects exercise capacity in a collaboration with Dr. Lessard. Colonies
of bacteria residing in our guts have a powerful impact on our health.
Exercise is an important component of a healthy lifestyle meant to ward
off diseases such as type 2 diabetes. Many people with metabolic
disorders are not able to exercise at the level needed to see such
benefits. Supplementing their microbiome using a probiotic capsule
containing Veillonella could give them the boost they need for
effective exercise. (Direct dosing with propionate pill would not work,
as the short chain fatty acid would be broken down by digestive juices
before it could take effect.) Dr. Scheiman has since spun this idea off
into a company targeted at athletes.
“The microbiome is such a
powerful metabolic engine,” says Dr. Kostic. This is one of the first
studies to directly show a strong example of symbiosis between microbes
and their human host.
“It’s very clear. It creates this positive
feedback loop. The host is producing something that this particular
microbe favors. Then in return, the microbe is creating something that
benefits the host,” he says. “This is a really important example of how
the microbiome has evolved ways to become this symbiotic presence in the
human host.”
This work was funded by the Synthetic Biology
platform at the Wyss Institute for Biologically Inspired Engineering at
Harvard University; National Institutes of Health/National Human Genome
Research Institute (NIH/NHGRI); National Institute of Diabetes Digestive
and Kidney Diseases (NIH/NIDDK); National Science Foundation (NSF);
National Library of Medicine; Smith Family Foundation Award for
Excellence in Biomedical Research; American Diabetes Association (ADA).
