A MICROSCOPIC VIEW OF THIS CHAPTER
• The intestinal microflora plays a role in immune system regulation.
• Probiotics promote healthy intestinal barriers and immune reactions.
• Lack of probiotics in infants may prevent proper immune maturation leading to allergies.
• Leaky gut allows allergens through the intestines and promotes allergies.
• Probiotics appear to prevent and treat certain atopic diseases (asthma, eczema).
• Eczema can be effectively treated with probiotics.
• Asthma may be prevented or treated with probiotics.
• Probiotics may play a role in food allergies.
What is an allergy? An allergy is an inappropriate immune reaction. In other words, the body is overreacting to an allergen (a substance that the body thinks is bad and defends itself against). Classic allergies are called type I hypersensitivity. In a classic allergy:
• An allergen enters the body.
• It interacts with immune cells called mast cells.
• The result is inflammation.
The inflammation can come in the form of itchy eyes, runny nose or diarrhea, depending on the allergen’s route of entry. Chronic allergies commonly present themselves as asthma or eczema, which are called atopic diseases. Atopic diseases are allergic diseases that occur with exposure to a substance that someone is allergic too. In rare instances, an extreme reaction to an allergen can occur in the body; this is called anaphylactic shock and can result in death. This is an inappropriate reaction by the immune system.
Atopic Diseases
Atopic diseases such as eczema and asthma occur when the immune system is misbehaving, resulting in an allergic reaction, in the form of inflammation. Genetic and environmental factors are involved. Atopic diseases have a strong hereditary component: if both parents are affected by an atopic disease (or one parent and a sibling), 40% of offspring will be affected. The genetic influence is multifactorial—no single gene carries asthma or eczema. Children with affected parents are more likely to become sensitive to an allergen and to develop allergic inflammation.
The growing incidence of allergies in the Western world has brought great attention to atopic diseases. Atopic diseases include eczema, asthma and other allergies. Increased cleanliness and reduced exposure to microbes are thought to be involved in the growing number of allergies in the Western world. As probiotics are known to keep the immune system in check, researchers are focusing on the interaction between the intestinal microflora and the immune system. In fact, the intestinal microflora is not just good at keeping the immune system in line, it is an important factor in regulating both the intestinal immune system and the systemic (entire body) immune system.
Probiotics keep the immune system in check.
Let’s start at the beginning with infants. It is hypothesized that the increasing rate of allergies has occurred at the same time as the reduction in children’s exposure to microbes. The use of infant formula and antibacterial cleaning products has reduced the exposure of probiotics and bad microbes to infants and may be a cause of the increased incidence of allergies we see today.
INFANT IMMUNITY AND ALLERGIES
The prevalence of atopic disease is steadily increasing in Western society. In fact, the increase has been so quick that it cannot be caused by genetics; there must be an environmental factor involved. Some scientists believe that the reason there are more allergies in Western society is due to our reduced exposure to microbes at an early age. This is called the hygiene hypothesis. Strict hygiene, smaller family sizes, better health-care and sterile food, all restrict our exposure to microbes as infants. The hygiene hypothesis was suggested by David Strachan in 1989, as data was starting to show an increase in the number of people suffering from allergies. The Center for Disease Control and Prevention in the United States reported that the prevalence of asthma in the United States has doubled from approximately 6.8 million in 1978 to more than 15 million in 1998. In addition, about 5% of the U. S. population has asthma, an allergy-related disease, with the highest percentage being in children, five to 14 years of age. Allergies are a growing problem in our society.
An allergy is an exaggerated reaction by the body to a substance called an allergen. Allergens can be a substance that causes disease such as venom, or they can be a relatively safe substance such as pollen or even the body’s own cells. To have an allergy, an individual is said to be sensitized to an allergen. There are many factors that are thought to increase your chances of becoming sensitized, including inflammation in your intestinal tract. An inflamed intestinal tract has wider gaps between cells, which allow allergens to access your body through your circulatory system and cause allergic reactions.
The atopic diseases (eczema and asthma) are the most common chronic diseases of childhood, affecting about one in four children in developed countries.
Inflammation of the intestinal tract can be regulated by probiotics. In fact, probiotics correct lymphocyte (white blood cell) imbalances. Probiotics are powerful stimulators of chemicals that control inflammation called inflammatory mediators, e.g., Th1 cytokines, IL-12 and IFN-gamma. Some species of Lactobacilli and Bifidobacilli improve the intestine’s ability to process allergens that have been ingested in the diet. Thus, a healthy microflora in the intestinal tract is vital in regulating the immune response and in preventing and treating allergies.
Early exposure of the blood to allergens is thought to increase the likelihood of developing allergies; thus, reducing the ability of these allergens to gain access to your blood may be vital in reducing the prevalence of allergies. Probiotics can control intestinal inflammation and reduce any gaps through which allergens can gain access to your blood. In other words, probiotics can reduce the chance of having allergic reactions. Thus, it is possible that the presence of probiotics in infants can reduce the chance of them developing allergies.
Probiotics first enter a baby immediately after birth. Research has confirmed that the presence of probiotics in the intestine leads to the maturation of the immune system. The maturation of the immune system in many infants is reduced due to less exposure to probiotics; this is particularly true of those who are bottle fed. This lack of probiotic ingestion in bottle-fed infants is known to have consequences. In several studies infants who have atopic diseases tend to have increased clostridia (a bad microbe) and fewer Bifidobacteria in their stools, indicating an unhealthy intestinal microflora. Atopic disease in infants is associated with having an unhealthy or abnormal microflora.
Probiotics may prevent the development of allergies. A number of studies have investigated the effects of supplementing both expecting mothers and infants with probiotics. The research shows that probiotics play a role in allergy (atopic disease) development in children. Let’s look at what research has found and which probiotic strains appear to be most effective against various forms of atopic diseases.
ATOPIC DERMATITIS
What is atopic dermatitis? Atopic dermatitis, or eczema, is a skin disease characterized by areas of severe itching, redness, scaling, and loss of the surface of the skin. Chronic presence of the rash results in thickening of the skin, as people will constantly scratch and rub at it. It is the most common of the many types of eczema.
Atopic dermatitis is frequently associated with other atopic (allergic) disorders, especially asthma and allergic rhinitis (hayfever). Atopic dermatitis is attributed to a dysfunction or problem with the immune system. This disease usually affects young children on the face, the elbows and knees. Older children and adults are usually affected on the sides of the neck and on the inside of the elbow and knee.
Atopic dermatitis is commonly seen in infants and is thought to be related to the immune system. As the immune system is greatly affected by the microflora introduced at birth, scientists have questioned whether atopic dermatitis is associated with a lack of probiotic presence at a young age. Breast milk contains probiotics which support a healthy gastrointestinal tract in infants. The use of infant formulas reduces an infant’s exposure to probiotics. As well, when a child is weaned from breast milk, his or her intake of probiotics drops. These two circumstances result in a decrease in intestinal probiotics and can allow bad microbes to enter the intestinal tract, colonize, cause inflammation and thus increase the potential for allergy development.
The cost of atopic dermatitis in Canada is estimated to be $1.4 billion annually.
Probiotics Help Fight Atopic Disease
Studies support the use of probiotics in infants with atopic dermatitis as a means to reduce the symptoms of this painful condition. According to research from the University of Western Australia, probiotic supplementation with L. fermentum for four months significantly reduced atopic dermatitis in young children aged six to 18 months. Ninety-two percent of the children receiving the probiotics had improved by the 16th week, compared to only 63% of the control group.
Other studies agree with these findings. A double-blind, placebo-controlled, crossover study gave two Lactobacillus strains (L. rhamnosus and L. reuteri) in combinations for six weeks to children aged one to 13 years old. Over 50% of the children taking the probiotic combination experienced improvements in their eczema. Only 15% of the children in the control group felt their symptoms had improved. A combination of L. rhamnosus and L. reuteri appears to be beneficial in the management of atopic dermatitis. L. reuteri in particular has been tested in numerous trials and is known to help treat children with eczema, and it may have some potential as a means of prevention.
A third study is worth mentioning here. An infant formula containing L. rhamnosus GG and B. lactis Bb-12 reduced the symptoms of allergy more quickly than standard treatment of hydrolyzed infant formula in young children with atopic dermatitis in a clinical trial. The reduction in symptoms occurred after two months of probiotic supplementation. This was the first clinical trial to show that specific probiotic strains can modify allergic inflammation. What is most amazing about these studies is that they prove how probiotics not only affect the immune system in the intestines, but they also affect the inflammatory system in other areas of the body.
Probiotics not only affect the intestines but also affect the inflammatory system in other areas of the body.
What effect might probiotic supplementation have in preventing atopic disease? A group of Finnish researchers examined infants who had evidence of atopic eczema and were thought to have an increased risk of developing allergic disease. The infants were given a formula supplemented with a probiotic, Bifidobacterium lactis. The study included a control group who were given an infant formula that contained no additional probiotics. As with all studies, it is important to measure the effects. A compound found in the blood, called IgE, can be used to measure inflammation. Interestingly, the level or amount of bad microbes (E. coli) was related to the level of IgE in these infants. As such, the researchers think that bad microbes are involved in the development of an allergic response. How does this work? The bad microbes change the gastrointestinal environment by producing toxins and damaging intestinal cells. If the researchers are correct, then supplementing infant formula with probiotic bacteria may decrease and prevent allergic reactions.
Microscopic Heroes
Why would probiotics help? Probiotics alter the immune system to encourage the body’s barriers to be strong, thereby reducing the ability of allergens to enter the blood or circulatory system. The inflammatory molecule IgA acts like a soldier that guards your intestines, preventing allergens from getting into your body. IgA acts as one of the first lines of defense against invaders. On the mucus surfaces of the body, such as those lining the gastrointestinal and respiratory tracts, IgA protects you from bad microbes and allergens that enter your body every time you breathe and ingest food. More specifically, IgA inhibits the ability of bad microbes to bind to the mucus surface of your body. Increasing the number of IgA molecules on the surface of the intestinal tract reduces the ability of bad microbes to attach and colonize.
The colonization of bad microbes in the intestinal tract can cause inflammation and is associated with allergy development. Thus, a way to increase IgA expression may help reduce the risk of developing an allergy. A study of infants with atopic dermatitis was conducted to see what effect probiotics have on IgA expression in the gastrointestinal tract. The study involved 230 infants who were given a placebo or a Lactobacillus rhamnosus GG milk mixture for four weeks. They found that the group consuming the probiotics had greater IgA secretion, suggesting that probiotics promote (upregulate) the defenses of the intestines. This research shows how probiotics beneficially alter inflammation and factors that promote allergy development.
Preventing Atopic Disease
Does this mean that probiotics can prevent the development of atopic dermatitis? At McMaster University in Canada, 1223 pregnant women carrying children at high-risk of developing atopic dermatitis were randomized to use a probiotic preparation or a placebo for two to four weeks before delivery. For sixth months after birth, their infants received the placebo or the same probiotics as their mother, plus galacto-oligosaccharides, a prebiotic. After two years, the incidence of allergic diseases (food allergy, eczema, asthma and allergic rhinitis) was evaluated. There were healthy amounts of Lactobacilli and Bifidobacterium species in the supplemented children. The children in the probiotic group had less atopic eczema. Probiotics can prevent eczema. The results suggest there is an inverse relationship between the presence of probiotics in an infant’s intestinal tract and the development of atopic diseases. In other words, probiotics do appear to reduce atopic disease.
Another study found that the prevalence of atopic eczema can be reduced in half with probiotic supplementation. The study involved a group of expectant mothers with a family history of allergies. The mothers were given the probiotic, L. rhamnosus GG. The mother’s subsequent newborn children were also supplemented with the probiotic for two years. Not only was the prevalence of eczema reduced by half, a four-year follow-up discovered that the preventative effect of the probiotic extended beyond infancy.
Not all of the research has found probiotic supplementation significantly reduces the incidence of atopic dermatitis. A group of researchers studied 178 infants who were considered to be at high risk of allergies because their mothers had allergies. At birth, the infants were randomized to receive either Lactobacillus supplements or a placebo daily for the first six months of life. The infants were assessed for immune function, atopic dermatitis and food allergies at six and 12 months of age. The researchers confirmed that the supplementation was working by checking for Lactobacillius colonization in stool samples; however, no significant differences were found between the groups at either follow-up point. Perhaps certain species are better than others at preventing eczema or there is a particular set or population level of probiotics required. More research is needed, but it appears that probiotics can help reduce eczema and perhaps offer some prevention against its development.
Inflammation and the Intestines: Summary
Probiotics are involved in controlling the inflammation of the intestinal system by promoting defense mechanisms and preventing bad microbes from growing there. Breast-feeding provides probiotics to infants. Infants who have been fed infant formula, and breast-fed infants post-weaning are at risk of invading microbes and can be susceptible to developing inflammation in the intestinal tract. Such inflammation increases the risk of developing allergies.
To date, the research, both in laboratory and clinical settings, suggests that the prevention of atopic eczema in high-risk infants is possible by changing the infant’s intestinal microflora with probiotics and prebiotics. Probiotics are effective treatments for atopic dermatitis in infants. Evidence also suggests that probiotics play an important role in controlling immune reactions throughout the body.
ASTHMA
Problems with the immune system in infancy are not only associated with atopic dermatitis but also with asthma, another atopic disease. Asthma is one of the most common chronic diseases of childhood and the most common causes of school absenteeism. Asthma is inflammation of the bronchial tubes causing airway obstruction, chest tightness, coughing and wheezing.
Asthma commonly develops in people with a history of atopic dermatitis. Studies have shown that school age children with atopic dermatitis (eczema) have an increased risk of developing asthma. This is not surprising as the mucus of the digestive and respiratory systems are very similar. They share many elements involved in immune defense and show some unity in the way they function in an immune response. Clinical investigation has found that people with asthma have an unhealthy microflora in their intestines and tend to have a permeable (leaky) gut. There is a connection between what happens to the mucus that lines the intestines and the lungs. In other words, the intestinal lining and the lungs are connected—a healthy gut can lead to healthy lungs.
A healthy gut can lead to healthy lungs.
What Is Asthma?
Asthma is a chronic disease that affects the airways of the lungs. The inside walls of the airways in a person with asthma are inflamed or swollen. This inflammation makes the airways very sensitive, and they tend to react strongly to allergens. A reaction by the airways to an allergen restricts the movement of air. This causes symptoms such as wheezing, coughing and chest tightness. Asthma cannot be cured, but it can be controlled in most individuals. An asthma attack is a worsening of symptoms in which the muscles around the airways tighten, making the airways narrower and causing less air to flow. An attack can be brought on by an interaction with an allergen or a physiological change in the body. Cells in the airways may also make more mucus than usual. This extra mucus causes further narrowing of the airways. Asthma is an inflammatory-related illness and thus controlling the immune system can help control asthma. The health of the intestinal tract, where 70% of the immune system lies, affects the overall health of the immune system. Unhealthy intestines can worsen asthma symptoms.
Probiotics have been shown to positively affect the atopic disease eczema. Do probiotics have the same positive effect on asthma? Probiotics improve the intestine’s ability to fight off invaders through their immunological barrier function which reduces the generation of chemicals that promote inflammation and prevents the intestines from becoming permeable. If probiotics are capable of reducing the production of chemicals that promote inflammation involved in allergic reactions, can probiotic supplementation alleviate the symptoms of asthma? Theoretically, this is possible. If probiotics are capable of preventing atopic dermatitis, it is possible that probiotics may also prevent the development of asthma.
Very few clinical studies have found probiotics help fight asthma. Lactobacillus paracasei-33 is one probiotic species thought to offer benefits to children with asthma. Yet probiotics can play a role in asthma therapy or even prevention. In 2006, scientist Del Giudice and colleagues stated, “In clinical trials probiotics appear to be useful for the treatment of various clinical conditions such as food allergy, atopic dermatitis and allergic rhinitis and in primary prevention of atopy. We can hypothesize that it may be possible, in the future, to use probiotics in primary prevention of asthma.”
In 2005, over two million Canadians and about 30 million Americans were suffering from asthma.
Currently, a study is underway in the United States called the Trial of Infant Probiotic Supplementation to Prevent Asthma (TIPS). The TIPS study is based on the hygiene hypothesis, which you have already learned hypothesizes that little or no exposure to bacteria and viruses during a critical period of infancy can lead to problems in the immune system and result in diseases such as asthma. TIPS hopes to determine whether stimulating the immune system with a probiotic supplement, Lactobacillus rhamnosus GG, for the first six months of life can prevent or delay asthma development. The three-year study will include about 280 healthy, full-term babies with an increased risk of developing asthma, i.e., either their mother or father has this atopic disease. Studies are also underway in Europe. More will be understood about the potential for probiotics to reduce or treat asthma when the results of these trials are published.
It is not certain whether the ability of probiotics to help with asthma has to do with reducing the chances that the body can become sensitized (allergic to something) or has to do with the ability of probiotics to mature the immune system, which is important in defending against viral infections. There is much more to learn about asthma. With the growing number of children suffering from this disease, we will certainly see more research in this area in the coming years.
Asthma Summary
Probiotics are known to mediate inflammation. This raises the question as to whether probiotic therapy can be used to prevent and treat other inflammatory-based diseases, such as asthma. Population trends suggest that problems with the immune system early in life are linked with an increased risk of developing asthma. Research has suggested that there is a likely connection between probiotics and asthma. Preliminary research confirms that probiotics can improve the quality of life for those with asthma. Ongoing trials hope to give more conclusive answers to how and which probiotics can help treat and perhaps prevent asthma.
FOOD ALLERGIES
Common Sources of Food Allergies
Eggs
Fish
Milk
Peanuts
Shellfish
Soy
Tree Nuts
Wheat
A food allergy is an inappropriate immune system response. The body mistakenly believes a food or food particle is harmful. Once the immune system decides a particular food is harmful (labels it as an allergen), it creates specific antibodies to it. As such, the next time the food enters the body, the immune system releases massive amounts of chemicals, including histamine, in an attempt to protect the body from the allergen. These inflammatory chemicals trigger a cascade of allergic symptoms that can affect the skin, intestines, cardiovascular or respiratory system. It has been estimated that approximately 12 million Americans suffer from a food allergy. About 90% of food allergies are caused by soy, shellfish, peanuts, milk, eggs, wheat, tree nuts and fish. The most common action taken to prevent food allergy reactions is to avoid the allergen. However, in a single year, 236 food products were recalled because they contained an allergen not listed on the label or were contaminated with an allergen. Avoidance of a food allergen may not be enough—a means of prevention or treatment is needed.
Food Allergy versus Food Intolerance
A food intolerance does not involve the immune system. For example, the food intolerance to lactose, called lactose intolerance, is caused by a lack of the digestive enzyme lactase, which breaks lactose down into its digestible parts. A food allergy occurs when the immune system mistakenly thinks a food particle is foreign and thus elicits an immune or allergic reaction when the food is consumed. This will occur every time this food is consumed; your body has a memory for “foreign” substances.
Food allergies are related to the permeability of the intestinal lining. Inflammation in the intestines causes the lining to become more permeable (leaky), allowing allergens to enter the circulatory system (blood) and cause an allergic reaction. These allergens can include bad microbes and incompletely digested foods.
Normally, the transport of allergens through the intestinal lining to the blood is limited. Thus, a food allergy implies that there is increased leakage between the cells lining the intestinal wall. This is sometimes referred to as leaky gut syndrome. This leakage is thought to be caused by a change in the shape of the intestinal cells. This change in shape is caused by toxins that are released by bad microbes living in the intestinal tract. Probiotics are well known to inhibit the presence of bad microbes and reduce the amount of toxins in the intestines. As such, probiotics may prevent leaky gut. Preventing leaky gut can help prevent the uptake of allergens, thus preventing the development of food allergies. Also, by reducing intestinal permeability in those who have food allergies, probiotics may prevent the development of other atopic diseases.
There are three ways in which probiotics are hypothesized to offer beneficial effects in the individuals with food allergies:
1. Children with a food allergy have an increased intestinal permeability. Probiotics have been shown to reverse this, reducing the permeability of the intestines, preventing or treating food allergies.
2. Research has proven that probiotics increase IgA in the intestines. IgA reduces the ability of microbes to adhere to the intestinal lining. This defense is frequently defective in children with food allergies.
3. Changes in number and type of intestinal microbes are common in allergic individuals. Probiotics have the ability to promote a healthy, normal intestinal microflora, thus reducing the development of allergies.
Food Allergies: Summary
Probitics help control the immune reaction to allergies and as such are thought to prevent food allergies. A research study investigated whether probiotics can prevent food allergy development by giving Bifidobacterium bifidum and Lactobacillus casei to mice with induced allergies. The probiotic decreased the allergic response and appeared to prevent the allergy. Human clinical trials are coming and great excitement lies ahead in the scientific community. If probiotics can in fact prevent or treat food allergies, a great number of people will be helped.
Fatty Inflammation
Dietary lipids, especially long-chain polyunsaturated fatty acids, e.g., omega-3 and omega-6 fatty acids, control immune function. These fats may change the ability of microbes to attach to the intestinal mucus lining. Good fats in the diet are another way to help control immune reactions associated with allergies, and promote a healthy intestine.
SUMMARY
There are more than 400 species of bacteria in the gastrointestinal tract. Only 30 to 40 of these species account for 99% of the microbes that make up the microflora of the human intestinal tract. Some of these species are probiotics. The presence of probiotics in the intestinal tract early in life helps the immune system to mature. Throughout life probiotics reduce the ability of allergens to gain entry into the body and control the immune system to reduce inappropriate reactions known as allergies.
Exposure to allergens early in life can sensitize individuals and lead to the development of allergies. The medical approach to allergic disease is evolving. Instead of trying to avoid allergens, probiotics are being used to prevent the development of allergies by ensuring the immune systems of infants are fully matured and activated. Today, experts believe that the increase in allergic diseases is linked to a lack of stimulation by microbes in the intestines of infants. Probiotics are thought to offer this stimulation. The use of infant formula and increased hygiene practices may be promoting the development of allergies in children by reducing their exposure to probiotics.
A lack of probiotics in the intestinal tract allows bad microbes to grow and release toxins that cause intestinal inflammation. Inflammation in the intestines allows allergens to gain access to the body, leading to sensitization. Probiotics can help reduce the exposure of the body to allergens by reducing the permeability of the intestines. Research suggests that supplementation with probiotics and prebiotics may help the development of a balanced immune defense in infants and children and may reduce the likelihood of developing allergic diseases such as eczema, asthma and food allergies. In clinical practice, probiotics are increasingly being used for these purposes. Probiotics may also help the immune system become strong enough to fight off viral infections, a possible factor in atopic diseases.
