Your gut is a reservoir of microorganisms – your gut microbiome.
On average, our gut microbiome has about a hundred trillion microbes or more at any given point.
Both the sheer number, as well as the diversity, of microorganisms we harbor in our guts are astounding.
And for the diversity of microbes in the gut, scientists say that microbial density of the colon is more numerous than that of any place on our planet.
Our gut microbiome is so important to many aspects of our physiology and behavior, so much so, that some scientists consider it to be an organ.
And, just like with any other organ, such as the liver or our brain, the gut microbiome can really shape and reshape our health.
Between any two individuals, our gut microbiomes are significantly different, to such a degree, that these differences in intestinal microbial composition may really affect each of our life paths.
Researchers found our individual microbiomes influence how each of us metabolizes medicine, how we heal, how we eat, even how we store fat – basically it has an effect on all aspects of our health and physiology.
Though subtle, these small variables can sometimes impact our lifestyle choices and our quality of life.
With our inner microbial ecosystem having so much influence on our health and lifestyle, it packs another important secret that we’ll explore deeper – how our gut microbiome may impact our motivation and performance during exercise.
That’s right, our gut microbial makeup may be what gets some of us to be highly motivated and physically excel, while in others, it keeps us a little more – sedentary.
Fascinating, isn’t it?
Before we dive into the science behind all of this, we need a quick review of what is actually meant by the gut microbiome.
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The gut microbiome, gut flora, gut microbiota, or intestinal microbiota are all synonymous.
They refer to the entire composition of an individual’s digestive tract microbial flora at a given point in time. Though mostly bacteria, the human gut microbiome also contains viruses, fungi, and other microbes.
There may be microbes in your gut, which confer positive impacts on your physiology and metabolism – like reducing your chances of liver disease, for example.
On the other hand, you may harbor other types of microbes that make you more vulnerable to illnesses.
Your gut microbiome may affect both the motivation to exercise and how you perform in those activities. Multiple scientific publications provide evidence to this fact.
In a recent study, veteran Professor George Church at Harvard Medical School collaborated with Dr. Aleksandar Kostic to learn more about the microbial composition and health.
Since gut microbiomes vary significantly between healthy and unhealthy individuals, they wanted to see if there was something special in the gut microbiome of athletes – which might account for, at least to some extent, why athletes perform so well compared to everyone else.
The results were groundbreaking.
Their research was published in the summer of 2019 in Nature Medicine. Compared to the general population, top-tier athletes, successful marathon runners, for example, have a higher proportion of bacteria from the genus Veillonella in their gut.
One of the “good guys” in your gut.
For proof of concept, they isolated a specific strain of bacteria – Veillonella atypica, from the stool of marathon runners, and put it into the gut of laboratory mice.
This technique is known as Fecal Microbiota Transplantation (FMT).What they found was that mice with the stool transplant of elite marathon runners increased their treadmill run time before they got exhausted.
Figure 1. Fecal microbiota transplant affects athletic endurance and performance in mice.
The biochemical mechanism explaining this observation was just as fascinating. It is depicted in figure 2. Here is the step-by-step explanation that the authors proposed in this study.
Figure 2. Schematic representation of how the gut microbiome affects exercise performance in trained athletes such as marathon runners. Researchers hypothesize that a higher amount of lactate present in athletes provides Veillonella an advantage to colonize, which then leads to an increase in lactic acid conversion to propionate.
Lactic acid is produced in the muscles when we exercise. And, athletes produce a lot of lactate in their muscles during their high physical activities.
The researchers showed exercise-induced lactic acid crosses the gut barrier and through systemic circulation, reaches the intestinal lumen where it was not initially produced.
Because of this reason, guts of trained athletes have higher levels of lactate reaching their intestines from systemic blood circulation.
The authors of this study hypothesize that this high level of lactate in the athletes' intestines somehow provides a selective growth and colonization advantage to Veillonella that prefer lactate as their nutritional source. So, Veillonella numbers increase due to the high availability of lactate in the guts of athletes.
This might explain why the gut microbiome of trained athletes have an increased number of Veillonella bacteria compared to the general population.
And in turn, this increased population of Veillonella metabolizes lactate into propionate in the athletes' colons, which ultimately improves exercise performance of the host.
This increased level of propionate that was produced from lactic acid conversion in the gut, in this case, was one of the major reasons, if not the main, behind the enhanced exercise performance phenotype.
Indeed, the authors found that intrarectal administration of propionate in mice improved exercise efficiency just like it did with an FMT of Veillonella.
How propionate improved exercise performance is not clear yet. Propionate has been shown in other studies to increase heart rate and maximal oxygen consumption, as well as affect blood pressure in mice (Scheiman et al., 2019).
In humans, propionate increases resting energy utilization and lipid catabolism.
The authors hypothesize that propionate might improve exercise performance by one or more of these mechanisms.
The other possibility is that, in mice with better exercise capability, the lactic acid being produced as a by-product of exercise is eliminated from the body faster by the higher numbers of Veillonella in their guts.
However, the results of this study indicated that lactic acid clearance from the systemic circulation is not that much affected by gut Veillonella. Indeed, the scientists found regardless of whether Veillonella was present in the mouse guts or not, it did not affect the rate of lactate clearance from the systemic physiology.
So, the authors concluded that perceivably, it is the higher production of propionate in the gut due to the Veillonella that explains why trained athletes do better in exercise as compared to the general population.
In another 2019 study, a team of researchers from France, showed the connection between host gut microbiome and exercise endurance.
As a mechanism, this team found that good microbes in an animal’s gut may optimize its muscle function, which has a very strong impact of exercise performance.
Toward the end of 2022, Lenka Dohnalová and Christoph Thaiss Ph.D. at the University of Pennsylvania Medical School, along with their peers, published a study in Nature that changed some of our original assumptions many ways.
For one, Dohnalová and Thaiss provided evidence that an animal’s gut microbiome may influence an animal’s motivation for doing exercise.
Further, the team showed that this motivational circuitry involved a complex gut-brain signaling, which was under direct influence of the gut microbiome.
They first made an interesting discovery that lab mice of various genetic backgrounds exhibited marked variability in their endurance while running on treadmills or in similar other exercises.As shown in figure 3, the researchers did a detailed profiling of these mice.
Figure 3. Detailed profiling of genetically diverse mice that exhibited differences in their capacities to exercise.
However, differences in host genetics could not explain the differences in exercise endurance in these mouse strains.
Additionally, even detailed physiological and metabolic analysis could not explain why these animals differed from each other in terms of exercise performance.
Since gut microbiome differences confer a lot of interesting phenotypes to the host, including behavioral patterns, the researchers asked a fundamental question: do the differences in gut microbiome compositions in these mice explain their different capacity for exercise?
To answer their question, they used a two-pronged approach.
First, the authors performed “gain-of function (microbiome transplantation)” experiments.
In these assays, when germ-free mice (mice with no gut microbiome) were administered FMT from high-performance mice, these germ-free mice became good at exercising as measured by running on treadmills or wheels.
Conversely, as depicted in figure 4, germ-free mice that received FMT from mice that demonstrated less motivation for exercise, exhibited less exercise motivation following the corresponding FMT.
Second, they depleted the mice of their gut microbiome using a regimen of antibiotics, performing what is called a microbiome depletion assay.
In the authors’ own words, “Microbiota ablation with broad-spectrum antibiotics diminished exercise performance on both running wheels and treadmills (Dohnalová et al., 2022).”
In other words, when mice, under study, were given a course of broad-spectrum antibiotics, their gut microbiome was killed. Importantly, exercise performances of these mice were also reduced simultaneously. This suggested a strong correlation between the gut microbiome composition of a mouse and the animal’s corresponding exercise performance.
As an extension to this experiment, the research team shifted the whole experimental setup from outbred to inbred C57BL6/J mice, to have every mouse at the same baseline of genetics.
In these mice, to quote the authors, "Microbiome ablation by broad-spectrum antibiotics reduced both treadmill and running wheel performance by about 50%.”
Further, once antibiotic treatment was stopped in these mice, exercise performance was once again restored, showing a strong causal correlation.
However, at this point, it was not clear whether this 50% reduction in exercise performance following antibiotic treatment was indeed due to gut microbiome depletion in these mice, or perhaps due to some side-effects of oral antibiotics that were administered.
To answer this question, the scientists explained that they “performed exercise tests under sterile conditions with germ-free mice, which showed a similarly reduced performance," to quote the study authors in their paper published in Nature (Dohnalová et al., 2022).
In other words, this showed that the intact healthy gut microbiota, which is missing in germ-free mice, was required for optimal exercise performance in mice.
Additionally, once these germ-free mice were no longer germ free, that is, they were kept like regular mice in the lab, exercise performance improved.
These observations supported the hypothesis that the gut microbiome composition is correlated with exercise performance.
Further, exercise performance was again restored once antibiotic was stopped or when microbiota was established in the guts of germ-free mice.
Figure 4. Proof of concept that gut microbiome affects motivation to exercise.
These results demonstrate that differences in the gut microbiome composition between different mice were responsible for their observed variability in exercise performance.
This team of researchers really increased the impact of their findings by figuring out the mechanism behind their observations, which connected the gut with the brain. And the gut microbiome governing gut-brain crosstalk.
Since the gut microbiome apparently affected the motivation of the lab animals for exercise, these scientists tested whether the gut microbiome had any influence on a region of the brain known as the striatum and on the neurotransmitter dopamine.
This is because dopamine is a key determinant of motivation, and it does so by stimulating neurons in the striatum.
Using a fluorescent dopamine sensor, the team measured whether dopamine levels changed during and after exercise in these mice.
More dopamine associated with exercise meant more motivation for exercise and a sense of gratification.
Remarkably, dopamine levels seemed to increase only in mice that had a microbiome in their guts, but not in those in which the gut microbiome was ablated by antibiotic treatment.
Further, if mice were treated with a drug that blocks dopamine signaling, it had the same effect on exercise motivation as with microbiota depletion via antibiotics.
All these data indicate that the effect this team of scientists had seen of the gut microbiome on exercise motivation in mice was perceivably due to modulation of dopamine signaling, which ultimately affected the striatum region of the brain.
As an additional step in putting all the pieces together in this new signaling puzzle, the study also showed that the gut microbes that increased a mouse’s motivation for exercise, synthesize a class of molecules known as fatty acid amides (FAA).
They found evidence that these FAA molecules are the actual chemical players that relay the signal from the gut to the brain.
In fact, they showed in this study that even in mice where the gut microbiome has been killed with antibiotics, supplementing the diet with FAAs increase their motivation to exercise.
We are perhaps approaching that day in bioscience advancement where if you lack the motivation to go to the gym, you pop in a magic pill – maybe FAA capsule, and suddenly you are all charged and motivated to jump on the treadmill!
Dohnalova et al. 2022. A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature. 612(739-742)
Hsu et al. 2015. Effect of intestinal microbiota on exercise performance in mice. J Strength Cond Res. 29(2): 552-8
Li et al. 2022. An exercise-inducible metabolite that suppresses feeding and obesity. Nature. 606, 785-790
Nay et al. 2019. Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis. Am J Physiol Endocrinol Metab. 317(1): E158-171
Okamoto et al. 2019. Microbiome potentiates endurance exercise through intestinal acetate production. Am J Physiol Endocrinol Metab
Scheiman et al. 2019. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nature medicine. 25, 1104-1109
Thursby and Juge. 2017. Introduction to the human gut microbiota. J Biochem. 474(11): 1823–1836