immunity-in-olympics-inforgraphic

Our immunity is often a forgotten part of our nutrition plan for optimal recovery. Intense exercise weakens our immunity because of the impact on our gut – an organ that is 70% of our immune system. A weakened gut leads to an open window for opportunistic, bad bacteria to invade and cause infection. This susceptibility can disrupt training – which can decrease sport performance – or require withdrawal from a competition. 

Fortunately, good gut microbiota can help make sure your hours of investment in training are worthwhile. Some gut microbes work with our gut and immune cells to take care of disturbances to immunity that result from high levels of physical and environmental stress.

In this blog, we’ll discuss:

  • The relationship between immunity, the gut and microbiota
  • How probiotics strengthen immunity
  • The negative effects of intense exercise on our gut
  • The effects of probiotic supplementation in athletes 

Athletes undergoing endurance training balance a fine line between enhancing health through exercise and hurting it. Exercise places physical stress on the gut, which lowers immunity. This is inevitable, but probiotics may be a simple nutritional intervention to fight the stress. 

The Relationship Between the Immunity, the Gut and Microbiota

The gastrointestinal (GI) tract is the most important part of our body’s defense system – especially because it’s 70% of our immunity. The intestine has the most lymphoid tissue – the lymphatic system is part of the circulatory system and a critical part of the immune system. These are important components of the gut: 

Mucous layer. The first-line-of-defense against invading pathogens the thick mucous layer (i.e., the innermost layer of the GI tract that is only one cell thick) surrounding the lumen (i.e., open space within the gut). It has two major functions. First, it needs to absorb nutrients. Second, it needs to guard against infectious, opportunistic pathogens because this intestinal barrier separates bacteria from our gut epithelium (i.e., a layer of cells that absorbs healthful substances and provides a barrier against bad substances). Mucus inhibits bad bacteria from colonizing by trapping and removing them so that they don’t enter our internal circulation. 

The mucosal layer comes in direct contact with digested food, which has antigens, and microorganisms in the gut lumen so it has many anti-microbial factors such as immunoglobulin (Ig)A, defensins, mucins and enzymes. IgA is needed to protect the mucosal surface. The secretion of IgA antibodies in the gut can lead to an immune response that affects the immune response at other mucosal surfaces in the body, such as within the respiratory tract.

Dysregulation, or complications, with the mucosal immune system underlies many inflammatory illnesses (e.g., ulcerative colitis, celiac disease) and increases susceptibility to cancer and infections. Essentially, it’s the anti-microbial proteins and secretory immunoglobulins that enhance the mucosal layer as a protective layer.

Gut epithelium. The epithelial layer spans the inner surface of the intestine. Cell junctions (proteins) connect epithelial cells. Of these junctions, tight junctions provide the most important physical barrier that is selective in what is allowed in and out (e.g., ions and small molecules). Aside from a physical barrier, it also facilitates communication between luminal contents and gut-associated lymphoid tissue (explained below). These cells have Toll-like Receptors (TLRs) that can recognize the good and bad bacteria and the toxic products of bad bacteria. When the TLRs recognize the pathogens, the epithelial cells attack the pathogens with an immune response. The role of probiotics is to regulate GI tract immunity by communicating with different receptors on the epithelium.

Gut-associated lymphoid tissue (GALT). The GI immune system is usually referred to as GALT, which protects the body from invasion. GALT is organized in structures called Peyer’s patches, which act like immune sensors (i.e., surveillance cameras). GALT stores immune cells (e.g., T helper cells and B lymphocytes) that attack and defend from pathogens. M cells cover the Peyer’s patches and coordinate immune defense. They take antigens and bad bacteria from the gut to certain immune cells that either activate or inhibit an immune response. Under the epithelial layer, dendritic cells (DCs) can either ignore or respond to invading antigens and bacteria.6 DCs can tell T-cells to release pro- or anti-inflammatory cytokines (i.e., proteins used in cell signaling, especially important in the immune system). 

A healthy immune system is maintained by the extensive, friendly interaction between gut microbiota and our mucosal immune system. When there’s an unhealthy gut environment, the mucin barrier weakens. This allows microbes to invade the epithelium and – ultimately – cause inflammation.  Essentially, our immune system needs to have an appropriate balance between tolerating good gut microbiota and defending against bad bacteria.

Factors in athletic training and competition that affect immune function

Factors in athletic training and competition that affect immune function

Probiotic Action to Strengthen Immunity

Maintaining the gut barrier is critical, especially in response to the consequences of intense exercise (explained below). Probiotic actions that modify and modulate different parts of the gut help strengthen the gut. Here’s how good gut bacteria strengthen our immunity:

Enhance the gut barrier. This is one of most important benefits. Probiotics can regulate the number of tight junction proteins between cells and can prevent or reverse the consequences of the bad bacteria. Many probiotic strains such as Lactobacillus plantarum, Bifidobacterium longum and L. rhamnosus positively impact tight junctions and intestinal barrier function. Reducing gut inflammation by reducing cytokine and reactive oxygen species (ROS) production also strengthens the barrier. 

The protein zonulin, released from the liver and gut, regulates the open spaces between cells of the gut (i.e., tight junctions between cells) and serves as a biomarker to estimate intestinal barrier integrity. Normal functioning allows nutrients and other molecules to enter and leave the gut. However, leaky gut causes the spaces between cells to open too much, which allows protein molecules to enter the blood and potentially causes an immune reaction. Not only that, other substances in the gut, such as bacteria, can enter, which creates inflammation and makes the liver work harder to get rid of the unwanted products.

Higher amounts of zonulin means changes in tight junction integrity and increased GI permeability. Zonulin is considered an acceptable biomarker to evaluate exercise-induced intestinal barrier disturbances, as evidenced by higher zonulin levels in the feces of humans,30 including athletes. The two main triggers activating zonulin are gut bacteria and gluten. 

Measuring zonulin in feces or blood serum is feasible, which makes it practical for athletes to test so that they can evaluate whether or not they need a dietary intervention. Decreased gut barrier function is triggered by changes in zonulin-activating gut microbiota, which can lead to inflammation. 

A randomized, double-blinded placebo-controlled trial investigated probiotic supplementation on biomarkers of intestinal barrier, oxidation and inflammation in 23 trained men following rest and intense exercise. The men either received a supplement containing six probiotic strains (B. bifidum, B. lactis, Enterococcus faecium, L. acidophilus, L. brevis, and L. lactis at 1 billion CFU/day) or placebo one hour before a meal for 14 weeks. 

Breakfast was the same for each participant before each exercise test to prevent differences in nutrients. Participants were not allowed to exercise three days before any exercise test. The men used an exercise bike to complete an intensive 90-minute exercise at the beginning of the experiment and after 14 weeks.

The results:

  • Average concentrations of zonulin at baseline were slightly above normal for both groups
  • Following 14 weeks of supplementation, the probiotic supplement significantly decreased zonulin levels by >20% compared to placebo

The decrease in zonulin went from slightly above normal at baseline (<30 ng/mL) to normal range following 14 weeks. It was suggested that the subjects might have had a slight increase in intestinal permeability at baseline, which could have resulted due to intense exercise training. It was concluded that appropriate probiotic supplementation may improve intestinal barrier function. 

The reason for improved intestinal barrier function is suggested to be the result of probiotics that can activate a particular TLR, which can improve epithelial resistance. Also, the probiotics may have outcompeted and/or replaced the zonulin-activating bacteria.  

Other effective strains with positive impacts on intestinal barrier function include B. infantisL. plantarumB. longum and L. rhamnosus.

Stop pathogenic bacteria. Probiotics can enhance host resistance by creating ecological niches in the mucosal layer to prevent pathogens from colonizing these surfaces. They do this by limiting the surface area for pathogenic bacteria to attach, decreasing nutrient availability for pathogens and secreting antimicrobial substances, such as short-chain fatty acids (SCFAs) – produced by bacteria when they digest non-digestible carbohydrate. SCFAs increase mucin production and increase the acidity of the gut, which stops the growth of bad bacteria and strengthens the gut barrier. 

Increase mucin production. Probiotics can strengthen the first line of defense – the mucosal layer. Probiotics, such as Lactobacillus, have been shown to influence mucin production.

Engage with immune cells. Immune cells (e.g., M cells, DCs) are constantly communicating with gut bacteria. Probiotics are taken up by M cells to engage with DCs and epithelial cells that activate responses when they take antigens to T helper cells (i.e., cells that help other immune cell activity by releasing cytokines that can regulate immune responses). Probiotics, such as L. plantarum and L. paracasei, can activate DCs, with L. paracasei being more immunomodulatory. Some strains can improve immune function by increasing the number of cells producing IgA and the amount of Th1 helper cells and natural killer T cells.

Aside from the GI tract, probiotics can strengthen immunity by their interaction with the common mucosal immune system, which links different parts of the GI tract (e.g., Peyer’s patches) to different sites within the GI tract and other mucosal surfaces, including the upper respiratory tract and genito-urinary tract.

Essentially, probiotics have a friendly relationship with the gut because they communicate with different parts of the gut immune system, maintain the gut barrier and prevent bad bacteria from colonizing. 

The Effects of Intense Exercise on the Gut

High-intensity exercise is immunosuppressive. Immune changes at the cellular level include a reduction in white blood cell function, which creates a window of opportunity for bad bacteria. Cortisol levels also increase as intense exercise is prolonged.

Intense exercise can also cause an acute inflammatory response by increasing the amount of pro-inflammatory cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-1, TNF receptors) and anti-inflammatory regulators (e.g., IL-10, IL-8).

Disturbances that Lead to Leaky Gut and Endotoxemia

The primary impact that weakens our intestinal wall barrier is the change in blood flow from the gut to skeletal muscle and the heart. This effect of changed blood flow is greater with higher intensity and prolonged exercise. Subsequently, the gut receives less:

  • Blood
  • Oxygen
  • Nutrients
  • Removal of metabolites

This hurts gut cells. In fact, GI complications are the consequence of blood moving away from the gut, which leads to abdominal cramps and diarrhea – major complaints experienced in endurance sports.  

A big increase in ROS also results from intense exercise, which leads to oxidation, cell communication changes and inflammation because of the cytokines released from the GALT immune cells. This leads to changes in the tight junction proteins and epithelial cell membranes – thus, lowering immunity. 

Water availability in the gut is another complication from intense exercise. The change in osmolality (i.e., chemical particles in the fluid component of blood) and gut movement may decrease the strength of the intestinal barrier. Increased gut barrier permeability is especially apparent in those exercising for a long time in the heat.

Reduced tight junction integrity between cells leads to a ‘leak’ that allows pathogens/toxins to pass easily through the intestine. The immune system responds to this leak, which results in inflammation and oxidative stress and a condition called endotoxemia. 

Endotoxemia is when endotoxins (i.e., a toxin in bacteria and released when the bacterial cell wall is destroyed) are in the blood. Lipopolysaccharide (LPS) – a major component of the outer membrane of certain bacteria – is an endotoxin of concern because it causes a strong immune response from a host. 

Blood flow away from the gut, ROS, water availability and exercising in the heat decrease the strength of the gut barrier, which increases gut permeability and leads to endotoxemia. This ‘leaky gut’ lowers the gut barrier’s protective function.

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The Consequences of a Weakened Gut Barrier

GI permeability (i.e., weakened gut barrier) increases following running on a treadmill at 80% VO2max (i.e., intense exercise), yet not at 40 or 60% VO2max. A leaky gut increases our susceptibility to infections and autoimmune diseases because of increased absorption of pathogens/toxins into the blood and tissues. 

Increased gut permeability – because of exercise – that results in endotoxemia was found in highly trained male triathletes. One study investigated whether or not GI complaints during ultra-endurance exercise was related blood moving away from the gut during exercise, which causes endotoxemia. Blood samples were taken from 29 athletes before, immediately after, and 1, 2 and 16 h following a long-distance triathlon to evaluate levels of LPS and cytokine production, such as the pro-inflammatory interleukin-6 (IL-6). 

GI symptoms were found in 93% of participants and 45% reported severe GI distress. Mild endotoxemia was found in 68% of the athletes immediately following the race. There was an increase of IL-6 (27x the original level) immediately after the race, which led to an acute-phase response of increase in C-reactive protein 16 h after the race. Ultimately, the researchers concluded that GI complaints in ultra-endurance athletes may have resulted from endotoxemia (LPS leakage) and increased cytokine levels. 

Effects of Probiotic Supplementation in Athletes:

The immunological effects of probiotic supplementation in athletes are promising. During stressful periods of training and competition, probiotics may:

Reverse T-Cell Defect

A study explored the effect of L. acidophilus (2 x 10*10 CFUs taken daily for four weeks) on immunity in 27 healthy and fatigued athletes. The fatigued athletes had a much lower level of IFNγ (i.e., a cytokine needed for immunity and produced by T cells) than the healthy athletes, which suggested a T cell defect. Following one month of supplementation, the fatigued athletes increased their IFNγ to the same level as the healthy athletes. These results were considered important because T-cells are critical in maintaining immunity and probiotic supplementation showed to reverse the T-cell defect. 

Lower Risk for Upper Respiratory Tract Infections

Higher exercise intensity as well as other stressors increase the risk of infection in athletes

Higher exercise intensity as well as other stressors increase the risk of infection in athletes

The immunosuppressive effect of exercise increases an athlete’s susceptibility to develop upper respiratory illness (URTI) (e.g., the common cold). Many athletes, especially elite athletes in rowing, cycling, swimming and triathlon, undertake prolonged intense exercise and are at increased risk for URTI resulting from intense training and competition.

URTIs are most common during the winter and adults usually have 2 to 4 URTIs per year. Increased risk for URTI could result from exercise-induced disturbances in immunity that gives opportunistic pathogens ability to cause infection. This is made worse when breathing cold, dry or polluted air. 

As previously mentioned, IgA is needed to help protect mucosal barriers. A study using 38 elite athletes from America’s Cup yacht race explored the effect of 50 weeks of training and competition on salivary IgA to determine if it was a risk factor for URTIs. Each week, samples of saliva were taken 38 h after exercise along with URTI, training load and perceived fatigue rating. The study found a decrease in salivary IgA over 3 weeks before an URTI along with a an increase of salivary IgA by week two following an URTI, which suggested lower salivary IgA increased the risk for a URTI. 

Strenuous exercise increases the amount of URTI in athletes. The increased risk for URTI during heavy training or following a marathon race was found in a study investigating the incidence of URTI of 2,311 runners in the week following the 1987 Olympic marathon.  

A 2015 meta-analysis investigated studies involving 3451 athletes and non-athletes and concluded that there may be a benefit to taking a daily probiotics supplement to reduce the symptoms of URTI.

Many other studies using athletes suggest that daily probiotics supplementation may lead to fewer days and severity of URTI. A study investigated a probiotics supplement during four months of winter endurance training in 84 men and women on URTIs and immunity. The highly active participants were randomized to either the probiotic (L. casei) or placebo daily for 16 weeks. Weekly trainings and illnesses were recorded. 

The results:

  • Athletes on probiotics supplementation were 36% less likely to experience 1 or more weeks with URTI symptoms compared to placebo
  • Number of URTIs was significantly higher in the placebo group than probiotics group
  • Probiotic group had higher levels of salivary IgA

Ultimately, habitual intake of the probiotics supplement may be helpful in reducing the number of URTIs in athletes. This could have been due to higher levels of saliva IgA, which the study suggests that probiotic supplementation helped maintain saliva IgA levels during a winter season of training and competition.

A double-blind, placebo-controlled cross-over study investigated the effect of L. fermentum supplementation for 28 days (1.2 x 1010 CFU per day) to improve the mucosal immune system of 20 elite male distance runners.41 The study assessed treadmill performance, immunity, training and illness. Cytokine levels, salivary IgA levels and duration and severity of respiratory tract infections were measured. 

L. fermentum decreased the number of days athletes had respiratory illness, which was suggested to be the result of improving T-cell function. 

Reduce GI Illness Symptoms & Duration

A study explored the effect of probiotic supplementation (109 CFU of L. fermentum) on GI illness symptoms and immunity using 99 competitive cyclists – men and women. Subjects were randomized to consume either one daily probiotic supplementation or placebo for 11 weeks during the winter. Participants recorded any symptoms of GI illness daily. To measure systemic immunity, blood samples were taken pre- and immediately post-exercise to determine cytokine concentrations. This was performed at the beginning and end of supplementation. To measure mucosal immunity, saliva samples were taken pre- and post-supplementation to measure salivary IgA concentrations. 

It was suggested that a 20-60% decrease in cytokine changes associated with probiotic supplementation could suggest enhanced immunoregulation. However, The study did not find a considerable relationship between cytokine changes – caused by exercise – and illness symptoms following supplementation. However, there was a major reduction in respiratory and GI symptoms after 77 days of supplementation for males, but not females. 

Another study investigated the effects of L. rhamnosus supplementation or placebo in 141 runners for three months before a marathon. The was no significant difference in the number of respiratory or GI illnesses two weeks after the marathon. However, the probiotic group had a shorter duration of GI symptoms, 2.9 days for the probiotic group versus 4.3 days for the placebo group. 

Counteract the Stress of Exercising in the Heat

A double blind crossover study used 10 male runners to evaluate if four weeks of daily probiotic supplementation (45 billion CFU of Lactobacillus, Bifidobacterium and Streptococcus strains, including L. acidophilus, L. rhamnosus, L. casei, L. plantarum, L. fermentum, B. lactis, and B. bifidum) or placebo would impact GI permeability while exercising in the heat. It is suggested that hyperthermia reduces the integrity of gut epithelial cells. The runners exercised to exhaustion at 80% of their VO2max at 95F and 40% humidity.

The results for probiotics supplementation:

  • Increased run time to exhaustion in the heat compared to placebo (37 min 44 sec vs. 33 min)
  • A small to moderate reduction in markers of GI permeability compared to placebo 

It was suggested that gut barrier integrity or immunomodulatory effects after probiotic supplementation may have improved performance, but ultimately, the mechanism was unclear. 

Probiotics: Immunonutrition for Sport Performance

Training is a stressor, and our bodies need to recover from this stress. High training volume and intensity without adequate recovery means the stress stays, which puts athletes at an increased risk for a weaker immunity and illness. Recovery from intense training requires an immunological aspect of sports nutrition: improving the intestinal barrier to reduce the athlete’s susceptibility to endotoxemia and cytokine production. In fact, current recommendations for immune-nutrition support in athletes includes taking a daily probiotic supplement that has at least 10 billion CFU. 

Probiotics help maintain the gut barrier, which strengthens immunity and leads to a secondary health benefit related to performance. Improved sport performance results from the ability to train harder and show up to competitions because you aren’t sidelined with an illness. Probiotics are a nutritional strategy to optimize recovery, which may limit illnesses affecting performance. 

by Katie Mark, MS

Katie Mark is currently a Master of Public Health candidate at Tufts University School of Medicine. She is a road cyclist working toward becoming a registered dietitian.

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