Nutrition and the new science of the "Gut-Brain connection"

Article by Scott Anderson

Trainers are always looking to gain an edge in performance. But what about their mental state? Are they jittery, distracted or disinterested? No matter how strong the horses, their heads must be in the game to succeed.

Surprisingly, much of that mental attitude is driven by gut health, which in turn depends on the collection of microbes that live there: the microbiota. In a horse, the microbiota is a tightly packed community of about 100 trillion microbes, composed of bacteria, archaea, fungi and protozoa. It colonises the entire GI tract but is largely concentrated in the hindgut, where it works to ferment the prebiotic fibre in forage. The microbial fermentation of fibre into fatty acids produces 70% of the animal’s energy requirements and without it, the horse couldn’t get sufficient energy from simple forage. Intriguingly, byproducts of that fermentation can affect the brain. 

It is easy to be sceptical about this gut-brain connection, but over the last decade, research has made it clear that gut microbes have an outsized influence on mood and behaviour. Microbes that improve mental state are called psychobiotics, and they may completely change the way you train and manage your horses. A horse’s health – and consequently its performance – starts in the gut.

Inflammation

When the microbiota is unbalanced by stress, diet or sickness, it is said to be dysbiotic. It loses diversity, and a handful of bacterial species compete for domination. Without the pushback of a diverse population, even beneficial bacteria can become pathogenic. Surprisingly, that can affect the brain. Multiple studies in various animal models have shown that transmitting faecal matter from one animal to another also transmits their mood. This demonstrates that a dysbiotic microbiota can reliably cause mental issues including anxiety and depression, thereby affecting performance. 

An important function of the microbiota is to fight off pathogens by outcompeting, starving or killing them. However, a dysbiotic microbiota is less diligent and may permit pathogens to damage the gut lining. A degraded gut lining can leak, allowing bacteria and toxins into the bloodstream. The heart then unwittingly pumps them to every organ in the body, including the brain. This makes the gut the primary source of infection in the body, which explains why 80% of the immune system is located around the intestines. Over time, a leaky gut can lead to chronic systemic inflammation, which weakens the blood-brain barrier and interferes with memory, cognition and mood. 

Inflammation is a major component of the gut-brain connection, but not the only one.

Neurotransmitters and hormones

Horses and humans use neurotransmitters to communicate between nerve cells. Brains and their attendant nerve bundles constitute a sophisticated network, which makes it somewhat alarming that microbes also produce neurotransmitters. Microbes use neurotransmitters to converse with each other, but also to converse with their host. The entire gut is enmeshed in nerve cells that are gathered up into the vagus nerve that travels to the brain. Microbial neurotransmitters including serotonin and dopamine thus allow certain microbes to communicate directly with the brain via the vagus nerve. We know this happens with specific bacteria, including Lactobacillus species, because when the vagus is severed, their psychobiotic effects disappear. 

As well as neurotransmitters, hormones are involved in gut-brain communications. The hypothalamus-pituitary-adrenal (HPA) axis controls the stress response in animals. The hypothalamus is located low in the brain and responds to stressors – such as a lurking predator – by producing hormones that stimulate the neighbouring pituitary, which then triggers the adrenal gland to produce cortisol, the stress hormone. Cortisol acts as a threat warning and causes the horse to ramp up glucose production, supplying the energy needed to escape a predator. This is the same hormonal circuit that trainers exploit for racing.

The HPA axis produces cortisol in response to stress. Cortisol inhibits the immune system, which in combination with a leaky gut allows pathogens to enter the bloodstream. Susequent systemic inflammation and vagal feedback lead to stereotypies.

The production of these hormones redirects energy to the heart, lungs and muscles at the expense of the immune system. From an evolutionary point of view, the tradeoff makes sense: first escape the predator and deal with infections later. After the danger has passed, cortisol causes the HPA to return to normal – the calm after the storm. 

However, continued stress disrupts that cycle, causing anxiety and diminishing the brain’s ability to store memories. This can dramatically interfere with training. Stress can also induce the release of norepinephrine, which promotes the growth of pathogenic bacteria including Campylobacter jejuni, Listeria, Helicobacter pylori, and Salmonella. Prolonged high cortisol levels can increase gut leakiness, potentially leading to infection and further compounding the situation. In the long term, continued stress leads to systemic inflammation, which is a precursor to problematic behaviours.

Short-chain fatty acids

When microbes consume proteins and fibre, they break them down into their constituent molecules, such as amino acids, fatty acids and sugars. These are the metabolites of the microbes. As well as neurotransmitters and hormones, the gut-brain conversation is mediated by metabolites like butyrate, an important short-chain fatty acid which plays multiple roles in the body. 

In the gut, butyrate serves as a preferred nutrient for the cell lining. It encourages the differentiation of stem cells to replenish gut cells that are routinely sloughed off or damaged. It plays an important role in the production of mucus – an essential part of gut protection – which coats the gut from mouth to anus. In the muscles, butyrate boosts the growth of skeletal muscle, crucial to athletic performance, as well as inducing the production of glucose, the primary muscle fuel. One-quarter of systemic glucose is driven by butyrate. In its gut-brain role, butyrate passes through the blood-brain barrier, where it nourishes and enhances the growth of new brain cells. 

These factors make butyrate a star player in the gut-brain connection. They also highlight the benefits of prebiotic fibre, especially when high-energy, low-fibre feeds are provided.

Starting a microbiota

We’ve explored the major pathways of the gut-brain connection: inflammation, neurotransmitters, hormones and fatty acids. Some of these pathways are at odds with each other. How does such a complicated system come together?

As mentioned, the microbiota is an animal’s first line of defence against pathogens, attacking and killing them often before the immune system is even aware of them. That means a healthy microbiota is an essential part of the immune system. However, the immune system is designed to attack foreign cells, which includes bacteria. For the microbiota to survive, the immune system must therefore learn to accept beneficial microbes. This lesson in tolerance needs to take place early in the foal’s development, or its immune system may forever fight its microbiota.

There are multiple ways nature ensures that foals get a good start on a microbiota that can peacefully coexist with the immune system. The first contribution to a protective microbiota comes from vaginal secretions that coat the foal during birth. After birth, microbes are included in the mare’s milk. These microbes are specially curated from the mare’s gut and transported to the milk glands by the lymphatic system. Mare’s milk also includes immune factors including immunoglobulins that help the foal to distinguish between microbial friends and foes. An additional way to enhance the microbiota is through coprophagia, the consumption of manure. Far from an aberration, foals eat their mother’s manure to buttress their microbiota. 

Microbes affect the growth and shape of neurons in various brain sites as the foal develops – a remarkable illustration of the importance of a healthy early gut microbiota. 

The cooperation between the immune system and the microbiota is inevitably complex. Certain commensal bacteria, including Clostridiales and Verrucomicrobia, may be able to pacify the immune system, thus inhibiting inflammation. This is a case where microbes manage the immune system, not the other way around. These convoluted immune-microbial interactions affect the mental state – and consequently the behaviour – of the horse, starting at birth.

Stereotypies

A 2020 study of 185 performance horses conducted by French researchers Léa Lansade and Núria Mach found that the microbiota, via the gut-brain connection, is more important to performance than genetics. They found that microbial differences contributed significantly to behavioural traits, both good and bad. A diversified and resilient microbiota can help horses better handle stressors including stalling, training, and trailering. A weakened or dysbiotic microbiota contributes to bad behaviours (stereotypies) and poor performance. 

The horses in this study were all carefully managed performance horses, yet the rates of stereotypies were surprisingly high. A kind of anxiety called hypervigilance was observed in three-quarters of the horses, and almost half displayed aggressive behaviour like kicking or biting. 

The study found that oral stereotypies like biting and cribbing were positively correlated with Acinetobacter and Solibacillus bacteria and negatively correlated with Cellulosilyticum and Terrisporobacter. Aggressive behaviour was positively correlated with Pseudomonas and negatively correlated with Anaeroplasma. 

Some of these behaviours can be corrected by certain Lactobacillus and Bacteroides species, making them psychobiotics. That these personality traits are correlated to gut microbes is truly remarkable. 

Intriguingly, the breed of a horse has very little impact on the makeup of its microbiota. Instead, the main contributor to the composition of the microbiota is diet. Feeding and supplements are thus key drivers of the horse’s mental state and performance. 

The gut-brain connection and training

How might the gut-brain connection affect your training practices? Here are some of the unexpected areas where the gut affects the brain and vice-versa:

High-energy feed. Horses evolved to subsist on low-energy, high-fibre forage and thus have the appropriate gut microbes to deal with it. A high-energy diet is absorbed quickly in the gut and can lead to a bloom in lactic acid-producing bacteria, which can negatively impact the colonic microbiota. High-energy feeds are designed to improve athletic output, but over time, too much grain can make a horse antisocial, anxious and easily spooked. This can damage performance—the very thing it is trying to enhance. Supplementary prebiotics may help to rebalance the microbiota on a high-starch regimen.

Changing feed regimens quickly. When you change feed, certain microbes will benefit, and others will suffer. If you do this too quickly, the microbiota can become unbalanced or dysbiotic. Slowly introducing new feeds helps to prevent overgrowth and allows a balanced collection of microbes to acclimate to a new regimen. 

Stress. Training, travelling and racing all contribute to stress in the horse. A balanced microbiota is resilient and can tolerate moderate amounts of stress. However, excessive stress can lead, via the HPA axis, to a leaky gut. Over time, it can result in systemic inflammation, stereotypies and poor performance.

Overuse of antibiotics. Antibiotics are lifesavers but are not without side effects. Oral antibiotics can kill beneficial gut microbes. This can lead to diarrhoea, adversely affecting performance. The effects of antibiotics on the microbiota can last for weeks and may contribute to depression and anxiety. 

Exercise and training. Exercise has a beneficial effect on the gut microbiota, up to a point. But too much exercise can promote gut permeability and inflammation, partly due to a lack of blood flow to the gut and consequent leakiness of the intestinal lining. Thus, overtraining can lead to depression and reduced performance.

Knowing how training affects the gut and how the gut affects the brain can improve outcomes. With a proper diet including sufficient prebiotic fibre to optimise microbiota health, a poor doer can be turned into a model athlete. 

References

Mach, Núria, Alice Ruet, Allison Clark, David Bars-Cortina, Yuliaxis Ramayo-Caldas, Elisa Crisci, Samuel Pennarun, et al. “Priming for Welfare: Gut Microbiota Is Associated with Equitation Conditions and Behavior in Horse Athletes.” Scientific Reports 10, no. 1 (May 20, 2020): 8311.

Bulmer, Louise S., Jo-Anne Murray, Neil M. Burns, Anna Garber, Francoise Wemelsfelder, Neil R. McEwan, and Peter M. Hastie. “High-Starch Diets Alter Equine Faecal Microbiota and Increase Behavioural Reactivity.” Scientific Reports 9, no. 1 (December 9, 2019): 18621. https://doi.org/10.1038/s41598-019-54039-8.

Lindenberg, F., L. Krych, W. Kot, J. Fielden, H. Frøkiær, G. van Galen, D. S. Nielsen, and A. K. Hansen. “Development of the Equine Gut Microbiota.” Scientific Reports 9, no. 1 (October 8, 2019): 14427.

Lindenberg, F., L. Krych, J. Fielden, W. Kot, H. Frøkiær, G. van Galen, D. S. Nielsen, and A. K. Hansen. “Expression of Immune Regulatory Genes Correlate with the Abundance of Specific Clostridiales and Verrucomicrobia Species in the Equine Ileum and Cecum.” Scientific Reports 9, no. 1 (September 3, 2019): 12674. 

Daniels, S. P., J. Leng, J. R. Swann, and C. J. Proudman. “Bugs and Drugs: A Systems Biology Approach to Characterising the Effect of Moxidectin on the Horse’s Faecal Microbiome.” Animal Microbiome 2, no. 1 (October 14, 2020): 38.