Allergies: genetics load the gun, but is your gut microbiome pulling the trigger?

Pollen from flowering plants, trees and grasses is the most widespread allergen source around the world (2), and spring and summer are the seasons which typically coincide with peak grass pollen counts in most major cities in Australia (with many peaks occurring between October and December) (3). Pollen, especially from grass, is a particularly significant trigger for the worsening of allergies in Australia during this time period, which includes a worsening of hay fever, asthma and even eczema symptoms (2). Eczema flare ups during the warmer months can be triggered by contact with airborne pollen and other allergens in some individuals but may be made worse by an increase in temperature which dries out skin and causes sweating, both factors which can inflame eczema-affected skin.

What causes allergies?

The immune system is designed to protect us against infections by harmful microorganisms. In people with allergies, parts of the immune system begin to recognise otherwise harmless substances such as pollen, animal dander, dust or foods as potentially harmful substances (2). For an individual, these substances are called allergens. Upon exposure to an allergen, it triggers an inflammatory immune response that is designed to help remove the allergen from the body. This response creates the symptoms we associate with allergies. For people whose immune system in the skin has been sensitised, it triggers eczema; sensitisation of the immune system in the lungs can trigger asthma, and sensitisation within the upper respiratory tract triggers hay fever.

Some allergens, such as foods, medications or insect bites and stings, can cause generalised allergic reactions which involve the skin, airways and circulatory system. The most severe form of this is known as anaphylaxis, which can be life threatening if not treated immediately (4). However, these are not seasonal allergies and can occur at any time.

The three former conditions, eczema, asthma and hayfever, are known as the ‘atopic triad’ due to the tendency for these conditions to occur together (5). This is likely because the sensitisation of the immune system in one part of the body can easily spread to other parts (6), and it is believed that genetics likely play a role in this predisposition for inappropriate immune behaviour (5). However, as the saying goes, “genetics only load the gun, the environment pulls the trigger”. This means that we can have a genetic susceptibility to something, such as allergies, but these genes need to be ‘switched on’ by something in our environment. In the case of allergies, it is believed that an unhealthy gut microbiota - the community of microorganisms living in the gut - may be responsible for ‘pulling the trigger’ (7).

The gut microbiome impacts the whole body

When we first discovered that our world was teeming with microscopic life, the ‘germ theory of disease’ quickly emerged. Microorganisms were considered to be the cause of all disease, and nothing more. Since that time, we have discovered that a healthy human is home to trillions of microorganisms and have recognised the complexities of the microbial world: a mixture of beneficial and infectious microorganisms, and those that lie somewhere in between.

We now know that the community of microorganisms living in our gut, known as the gut microbiome, can impact our health and influence the function of many of our vital organs and body systems - including our immune system. Many different microorganisms can live within the gut, each playing an important role and working together to create the conditions for a healthy gut and body. For this reason, diversity is one of the best markers of a healthy gut microbiota. When the diversity of the gut microbiota is disturbed, it can negatively impact our health. This is referred to as ‘gut dysbiosis’ and it has now been associated with many chronic diseases, including allergies (8).

Why does the immune system begin to react to allergens?

Seventy percent of the immune system is found along the lining of our digestive tract. As a potential point of entry for infectious microorganisms, the digestive system is heavily defended by immune tissue. It is also here where the immune system learns to differentiate between infectious and beneficial microorganisms and harmless substances such as pollen, animal dander, dust or foods (6). Interactions between the gut microbiota and the immune cells lying just below the intestinal cells are heavily involved in this process. Exposure to a variety of different microorganisms within the gut is critically important for the development of a healthy immune system which learns to differentiate between the harmless and the harmful in the gut, and mount appropriate responses (6).

In infancy, as a range of different microorganisms begin to colonise the gut, this process kicks into gear and it is thought to take several years for the immune system to fully mature. As immune tissue and cells in the digestive tract undergo this educational process in early life, what is learned is disseminated to immune tissue all around the body by the circulation of immune cells in the blood. However, if the type or quantity of microorganisms we are exposed to in early life changes or the composition of the gut microbiome is significantly disrupted it can also disrupt this process (9). As mentioned previously, this disruption to the gut microbiome is known as ‘gut dysbiosis’. As a result of gut dysbiosis, the risk of the immune system learning to become reactive to what should be harmless substances and the development of allergies is increased.

Indeed, alarming increases in allergies over the past thirty years (10) are now being attributed to reductions in the abundance and diversity of microorganisms within our gut microbiotas (11). This is believed to be caused by a number of different factors, including increased antibiotic use, excessive cleaning with antimicrobial substances, caesarean sections, and formula feeding. Scientists have called this theory the ‘hygiene hypothesis’, and it attributes the dramatic rise of allergies to alterations in our gut microbiota and the effect that has on our immune system (12).

How do these factors disrupt the gut microbiome?

Antibiotics are often broad-spectrum in their action, meaning they are able to kill bacteria responsible for infections as well as beneficial bacteria within the gut microbiome. There are also emerging links between chemicals used in household cleaning products and negative effects on the gut microbiome (13). Vaginal delivery helps to support the transmission of particular beneficial bacteria from mother to child as the baby interacts with the mother’s vaginal, skin and faecal microbiota during delivery, a benefit which caesarean deliveries do not provide (14). Of even more importance, breastfeeding provides particular types of prebiotics found in breast milk (called oligosaccharides) that are known to selectively feed beneficial bacteria and help to establish a healthy community within the infant gut. Unfortunately, baby formula is not yet able to replicate all of the benefits of breastfeeding on the gut microbiome and can alter the composition of the gut microbiome.

Evidence of the link between gut health and allergies

A growing body of research is supporting the link between gut microbiome disruption in early life and an increase in the risk of allergies. For example, a study published in 2013 had followed 14,541 children in the UK and found that exposure to antibiotics in the first two years of life was associated with a 1.75 x increased risk of developing asthma by age 7.5. The risk was increased with each number of antibiotic courses, with four or more courses leading to a 2.82 x greater risk of asthma by the same age (15). It has also been demonstrated that in infants, the gut microbiota of those who will go on to develop allergies is deficient in a specific group of bacteria called Bifidobacteria compared to those who don’t develop allergies in the future (16). These differences are also observed between those with allergies and those without. In animal studies, the transfer of the gut microbiota from healthy infants into germ-free mice protected them from developing an allergy to cow’s milk whereas the transfer of the gut microbiota from infants with cow’s milk allergy did not offer the same protection (17).

How to reduce the risk of developing allergies

The impact of the gut microbiome on the immune system and the expression of particular genes associated with allergies means that supporting a diverse and healthy gut microbiota during the early years of your children’s lives is one of the most important things you can do to help reduce their risk of developing allergies. Unfortunately, at the ages where it makes a difference to us, we have no say and depend on the supportive actions of our parents. Many factors which the research has found to protect against allergies are also those that support a diverse gut microbiome, such as growing up on a farm and growing up with pets in the first year of life, specifically dogs (18). These factors expose individuals to a range of different microorganisms that they wouldn’t otherwise encounter and are beneficial for our gut microbiome diversity. Breastfeeding also supports the establishment of a healthy gut microbiome which is rich in beneficial bifidobacteria (19) known to protect against allergies (20). A diet rich in plant foods, which provides important prebiotic fibres to feed the beneficial microorganisms in the gut, is also important when children begin eating solids (21). While antibiotics can’t be avoided when prescribed by a medical professional and are important life-saving interventions, specific probiotic strains can support the balance of beneficial gut bacteria during and after antibiotics and help to avoid unnecessary negative effects on the gut microbiome.

Probiotics are beneficial bacteria which can help to restore balance to the gut microbiota and provide additional health benefits to the human body while they are present in the digestive tract. However, not all probiotics offer the same benefits and this depends entirely on the specific strains being used. The probiotic strain Lactobacillus rhamnosus GG reduces the risk of antibiotic-associated diarrhoea in children and adults by 51%, which is supported by the highest level of scientific evidence (22). During antibiotic treatment, L. rhamnosus GG helps to prevent gut dysbiosis by preventing the overgrowth of potentially harmful microorganisms in the gut. There is also evidence that supplementing with specific probiotic strains during pregnancy can help to reduce the risk of allergies, specifically eczema, in the child. In a study involving 159 pregnant women, the administration of the same probiotic strain L. rhamnosus GG for 4 weeks before expected delivery and 6 months after delivery significantly reduced the risk of eczema in the first 7 years of their child’s life (23).

Can probiotics improve the management of allergies?

There are many strategies that you and your team of medical professionals may use to help manage and control your allergies depending on their severity, including avoiding triggers, medications and immunotherapy. The ability for the gut microbiome to impact the immune system and allergies has now led scientists to investigate if supplementation with specific probiotic strains may help to support a depleted gut microbiome and improve the management of pre-existing allergic conditions alongside standard medical care - with promising results.

In a study involving 43 children aged 0-11 with eczema, the supplementation with Lactobacillus salivarius LS01 significantly reduced the symptoms of eczema after four weeks with further improvements after eight weeks (24). Similarly, in a study involving 38 adults with eczema, those who received the same probiotic strain for 16 weeks had a 53% reduction in their symptom severity and a 55% improvement in their quality of life (25). In a study involving 422 children with allergic asthma, those children who took a combination of Lactobacillus salivarius LS01 with another probiotic strain, Bifidobacterium breve B632, alongside their prescribed medications had 64.2% fewer asthma exacerbations compared to those who took placebo alongside their prescribed medications (26).

While probiotics are not a replacement for medications prescribed by a medical practitioner for the treatment and management of allergies, the research is demonstrating that specific strains of probiotics may be a useful tool that can be used alongside these medications to help improve symptom control.

How to select the right probiotic for your unique needs

When looking to use a probiotic for a particular health concern, it’s important to use the same strains which have been shown to support that health concern in the research. Just like the microorganisms found naturally in your gut, specific probiotic strains such as Lactobacillus salivarius LS01, Bifidobacterium breve B632 and Lactobacillus rhamnosus GG can interact with the immune system lining the digestive tract. Because of this, they are able to provide benefits to the management of certain allergies. Each of these probiotic strains works slightly differently, and this is why certain strains and combinations of strains have been found to be effective for different allergic conditions.