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.
Veillonella
spp. are nonmotile, gram-negative diplococci that are the anaerobic counterpart of Neisseria.
Veillonella is part of the normal flora of the mouth and gastrointestinal tract and may be found in the vagina as well.
Although of limited pathogenicity, Veillonella is often mistaken for the more serious gonococcal infection.
Veillonella spp. are often regarded as contaminants; they are often associated with oral infections; bite wounds; head, neck, and various soft tissue infections; and they have also been implicated as pathogens in infections of the sinuses, lungs, heart, bone, and CNS.
Recent reports have also indicated their isolation in pure culture in septic arthritis and meningitis.
Veillonella
are gram-negative anaerobic cocci and belong to the family Veillonellaceae. Strains detected in oral cavities include Veillonella parvula, Veillonella atypic, and Veillonella dispar.
Veillonella parvula subsp. parvula
V. parvula subsp. parvula are gram-negative anaerobic cocci and are among the most common bacteria in the oral cavity. Cell characteristics are shown in Figure 3.21(A) and (B). The DNA GC content is 38% when analyzed by Tm or 41% when analyzed by Bd. The type strain is ATCC10790.
V. parvula subsp. parvula is a strict anaerobe. Several strains require putrescine and cadaverine in their growth medium. Characteristic colonies are shown in Figure 3.21(C) and (D).
The cells are relatively biochemically inactive when tested using classical biochemical tests. They are unable to ferment carbohydrate to acid and do not produce indole.
They appear negative with the catalase test but are able to reduce nitrate to nitrite.
V. parvula subsp. parvula is detected in saliva, on the tongue, and in plaques. They are able to utilize lactate produced by Streptococcus mutans, and are thus considered as beneficial bacteria in dental plaques. They form part of the normal human gut flora.
V. parvula subsp. parvula require strictly anaerobic conditions, forming small gray-white colonies on the surface of BHI blood agar.
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 Ph.D., TITLE., 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, Ph.D., then a researcher in the lab of George Church, Ph.D., 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.”
The metabolism of lactate impacts infant gut health and may lead to acute accumulation of lactate and/or H2 associated with pain and crying of colicky infants.
Because gut microbiota studies are limited due to ethical and safety concerns, in vitro fermentation models were developed as powerful tools to assess effects of environmental conditions on the gut microbiota.
In this study, we established a continuous colonic fermentation model (PolyFermS), inoculated with immobilized fecal microbiota and mimicking the proximal colon of 2-month-old infants. We investigated the effects of pH and retention time (RT) on lactate metabolism and of lactate-utilizing bacteria (LUB) exhibiting little or no H2 production.
We observed that a drop in pH from 6.0 to 5.0 increased the number of lactate-producing bacteria (LPB) and decreased LUB concomitantly with lactate accumulation.
Increasing RT from 5 to 10 h at pH 5.0 resulted in complete lactate consumption associated with increased LUB. Supplementation with dl-lactate (60 mM) to mimic lactate accumulation promoted propionate and butyrate production with no effect on acetate production.
We further demonstrated that lactate-utilizing Propionibacterium avidum was able to colonize the reactors 4 days after spiking, suggesting its ability to compete with other lactate-utilizing bacteria producing H2.
In conclusion, we showed that PolyFermS is a suitable model for mimicking young infant colonic microbiota. We report for the first time pH and RT as strong drivers for composition and metabolic activity of infant gut microbiota, especially for the metabolism of lactate, which is a key intermediate product for ecology and infant health.
IMPORTANCE
The metabolism of lactate is important for infant gut health and may lead to acute lactate and/or H2 accumulation, pain, and crying as observed in colicky infants.
Functional human studies often faced ethical challenges due to invasive medical procedures; thus, in this study, we implemented PolyFermS fermentation models to mimic the infant proximal colon, which were inoculated with immobilized fecal microbiota of two 2-month-old infants. We investigated the impact of pH, retention time, and accumulation of dl-lactate on microbiota composition and metabolic activity.
We found that a drop in pH from 6.0 to 5.0 led to increased LPB and decreased LUB concomitantly with lactate accumulation. Increasing the RT resulted in complete lactate consumption associated with increased LUB.
Our data highlight for the first time the impact of key abiotic factors on the metabolism of lactate, which is an important intermediate product for ecology and infant health.
More information: Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism, Nature Medicine (2019). DOI: 10.1038/s41591-019-0485-4 , https://www.nature.com/articles/s41591-019-0485-4
Journal information: Nature Medicine
Provided by Joslin Diabetes Center
