August/September 2022 Issue

CPE Monthly: The Role of Probiotics in Treating and Preventing Allergies
By Alexandria Hardy, RDN, LDN
Today’s Dietitian
Vol. 24, No. 6, P. 48

Suggested CDR Performance Indicators: 8.1.3, 8.1.4, 10.2.7, 10.2.9
CPE Level 2

Take this course and earn 2 CEUs on our Continuing Education Learning Library

The human body is host to hundreds of different microbial species.1 Heterogeneity of gut microflora is essential to a reduction of chronic disease, a proper immune response, the inflammatory response, and perhaps even a decreased development of allergic diseases.2,3 Exposure to certain strains of probiotics in the Bifidobacterium and Lactobacillus genera are thought to decrease the chance of an allergic disease presenting in early childhood, particularly between birth and toddlerhood.3 While allergies can develop at any age, they’re most likely to appear within the first three years of life. This may be because the intestinal microbiota is immature until around age 3.4

RDs should be equipped to evaluate the impact of regular probiotic consumption on some of the most common types of allergies per the World Health Organization (WHO). These include allergic rhinitis, atopic dermatitis (eczema), and food allergies.4

This continuing education course evaluates the evidence and research surrounding probiotics for individuals at risk of allergic diseases.

Probiotics and the Immune System
The gut microflora is comprised of a variety of bacteria, viruses, yeasts, fungi, and protozoa.4,5 The immune response, in the form of bacteria concentration, increases throughout the gastrointestinal (GI) tract until it reaches its peak concentration in the large intestine. There are an estimated 15,000 to 36,000 species of bacteria in the large intestine, with concentrations of 10^11 to 10^12 CFUs/g (colony-forming units per gram).4 The most common bacterial phyla are Firmicutes and Bacteroidetes, which make up 90% of the microbiota.6 The ratio of Firmicutes to Bacteroidetes (F/B ratio) is important because it helps maintain homeostasis in the large intestine, enabling normal immune responses.5

Firmicutes includes gram-positive bacteria from the more commonly known genera Bacillus, Clostridium, Enterococcus, Lactobacillus, and Ruminicoccus. Their common identifying feature is an inflexible cell wall. Bacteroidetes includes gram-negative bacteria genera Bacteroides, Alistipes, Parabacteroides, and Prevotella; these genera have flexible cell walls.5

Strains of Lactobacillus and Bifidobacterium are associated with the strongest immune response and therefore are likely to be most impactful for allergies. However, benefits are dose, strain, and age dependent. Lactobacillus strains induce an anti-inflammatory response and regulate signaling, while Bifidobacterium strains promote cell immunity while expressing antiviral activity. The Lactobacillus and Bifidobacterium strains also are the most commonly used in clinical trials examining efficacy of probiotics in certain conditions.4

F/B Ratio
The concentrations of gut microflora, which can evolve throughout an individual’s lifetime, are impacted by environment, ethnicity, diet, lifestyle, and antibiotics. The F/B ratio, a key metric of microflora concentration, should stay relatively stable or dysbiosis is likely to occur.5 Dysbiosis is a destabilization of gut microflora concentrations, which can cause immune system disruptions and potential allergic responses.6 Probiotic usage is one of several therapeutic strategies used to maintain equilibrium in the F/B ratio and support immune health while decreasing inflammation.5

Using probiotics to treat allergies is an example of therapeutic microbiology.4 Ideally, probiotic use would lead to an increase in immunoglobulin G antibodies, overriding the immunoglobulin E response and decreasing the intensity and frequency of allergy symptoms.7

Therapeutic Dosing of Probiotics
The WHO suggests that to confer benefits, probiotics must pass through the GI tract whole. This ensures that a minimum therapeutic level of a particular probiotic strain colonizes the gut. Recommendations suggest a minimum dose of 10^6 CFUs/g of viable cells. The main way to determine the intact survival and transit of probiotic products is to recover the strain via a stool sample and measure it in a dose-response study. By studying the remaining strain, researchers can determine a strain’s hardiness, beneficial effects, and better understand the quantity of probiotics needed to produce a positive response.

To put the minimum dose in perspective, consuming 100 g/day of probiotics yields about 10^9 CFUs viable cells in the upper GI tract, which indicates that regular probiotic consumption elicits a dose-response reaction.8

Defining Probiotics
In 2014, the International Scientific Association for Probiotics and Prebiotics defined probiotics as living microorganisms that can be beneficial to an individual if taken in proper quantities.9,10 These live bacteria can be found naturally occurring in food or taken in supplement form, generally to restore balance to the gut microbiota and diversify the intestinal flora.11,12 This restoration is increasingly needed, as chronic illness, environmental factors, and unhealthful lifestyle choices perpetuate inflammation.12

Sources of Probiotics
Probiotics naturally occur in some foods but are added to others. In 2019, adults worldwide spent more than $51 billion on probiotics, with regular use more common in women.13 Probiotics in both foods and supplements have been shown to be effective at bestowing benefits, but probiotic-rich foods tend to be less expensive and more easily accessible than probiotic supplements.9,11 A likely barrier to probiotic supplements is cost. For example, a 32-oz bottle of kefir typically costs $4 at the grocery store, while a 30-day bottle of probiotic supplements can cost $20 to $50 depending on the brand, ingredients, and source.

Dietary sources include foods that boast naturally occurring probiotics via bacterial fermentation and functional foods, which in this context are defined as foods that contain added probiotics.8 Dairy products such as kefir, yogurt, cultured buttermilk, and certain cheeses like pecorino, cheddar, and mozzarella contain strains of lactobacilli and bifidobacteria, which are able to survive in a low-pH environment.14 Miso, cured meats, tempeh, sauerkraut, beer, wine, kombucha, cocoa beans, vinegar, sourdough bread, kimchi, olives, pickles, fiber snacks, fruit and vegetable juices, and chocolate are other popular fermented foods that may contain probiotics.8,12,14,15 Many of these fermented foods have long been a part of diets across the globe, as they provide another way to preserve food. These probiotic foods contribute different flavors and textures to a variety of dietary patterns and may confer other health benefits.

Fermented foods, such as those that contain fermented yeast, fructooligosaccharides (FOS), or galactooligosaccharides (GOS), are a significant source of pre- and probiotics and are associated with decreased inflammation and oxidative stress.4 Cereal grains like millet and sorghum, some soy products, cabbage, legumes, and maize also contain varying amounts of probiotics when fermented or prebiotics in their natural state.14 Foods that contain naturally occurring probiotics generally are regarded as safe.4

Probiotics in Research
Yogurt, milk, and encapsulated probiotics are some of the most commonly used sources of probiotics in research. Strains and dosages may vary depending on whether the strain is naturally occurring or added in ingredient form.1,16 An example of this would be the strain Bifidobacterium animalis DN-173 010, which is found in a popular type of yogurt in the United States. Conversely, the strain Lactobacillus acidophilus LA5 is more commonly sold as an ingredient and Lactobacillus reuteri ATCC 55730 is the main strain in a brand name probiotic chewable tablet.1

Defining Prebiotics
A prebiotic is an indigestible substance, such as insoluble fiber, that benefits the gut microbiota, serving as a food source for probiotics. Prebiotics can withstand stomach acid, can’t be absorbed into the GI tract, and are fermented by the microbiota.17 Prebiotics aid in fermentation in the large intestine and are beneficial components of overall digestive health.2,9

Sources of Prebiotics
Most prebiotics are carbohydrates, mainly oligosaccharides, such as FOS, GOS, xylooligosaccharides, and inulin.9,17 Dietary sources of prebiotics include yacón—a tuberous root similar gastronomically to an apple or jicama—garlic, onion, asparagus, artichokes, and bananas.9,18,19 Chicory, sunchokes, sugar beets, barley, honey, rye, soybeans, peas, and brown and red seaweed are other examples of naturally occurring prebiotics.

Many of these dietary sources don’t naturally have a high enough concentration of prebiotics in the serving size in which they’re usually consumed to be considered therapeutic. To this end, consumers may choose to take a supplement to more easily reach an appropriate dose.12 Therapeutic dosages typically fall between 2.5 and 10 g/day and may yield mild to moderate side effects, primarily GI discomfort.17

Research currently is under way to evaluate whether stable FOS and GOS supplements can be produced on a large scale.17 The existing research on prebiotics as they relate to allergy treatment and prevention is scarce, with current studies delving into methods of administration for consumption.1

Defining Synbiotics
Synbiotics are a blend of pre- and probiotics found in dietary supplements and food ingredients; a common example is fructan.20 They may be helpful in not only preventing allergies but also treating them, mainly by decreasing the severity of various allergy symptoms that may otherwise lead to a reliance on medication.4

Allergies and Probiotics

Food Allergies
Between 240 million and 550 million people worldwide have a food allergy, defined as a negative reaction, either immediate or delayed, to a food allergen that impacts quality of life.4,21,22 In the United States, 3.9% of infants and children and 6.6% to 10% of adults suffer from some form of food allergy. This percentage has increased over the past several decades and is expected to continue to rise.4,22-25 Factors in urban environments may increase risk.4

The most common types of food allergies are cow’s milk and eggs in children and peanuts, tree nuts, wheat, soybeans, and shellfish in adults.4 Potentially allergenic foods are introduced to the body via skin contact or the GI tract.26 In the GI tract, the composition of the gut microflora greatly impacts immune function, which suggests that if an individual experiences frequent dysbiosis at a young age, food allergies are more likely to occur.26,27

Current nutritional interventions include breast-feeding when possible, using a whey-based partially hydrolyzed infant formula if not breast-feeding, and introducing a complementary diet beginning at the four-month mark for high-risk infants to help prevent food allergy. Various immunotherapies and gut microbiome–modifying therapies also are in the research phase, with the goal of determining what specific strains, dosages, immune-modulating nutrients, and delivery methods are most effective at treating or preventing food allergies.28

Probiotics are somewhat controversial when it comes to prevention or treatment of food allergies. There are insufficient data to support recommendations of a standardized specific probiotic strain or dosage. There also are few reviews that use food challenges to diagnose an allergy.21,29 Research from a study of 56 children aged 1 to 10 indicates that strains of Lactobacillus aren’t helpful in preventing or lessening severity of peanut allergy, even when used alongside oral immunotherapy.29,30 Conversely, a cohort of 60 infants aged 3 to 12 months who were administered a combination supplement of Bifidobacterium animalis subsp. lactis BB-12 and Streptococcus thermophilus experienced fewer GI symptoms related to milk allergy.29,31

If early intervention measures are taken—particularly dietary intake of probiotic-containing foods—probiotics are associated with a reduction in allergy development and symptom severity in certain populations.12,25 Allergies occur when the immune system is overstimulated by environmental matter (an allergen) and a physical reaction occurs. The diversity and homeostasis of an individual’s intestinal flora are involved in both the prevention and treatment of certain types of allergies.3

A gut microflora with an unbalanced environment can lead to allergenic disease. For example, an abundance of Clostridium difficile is associated with the development of allergies in children, and children without allergies tend to have a more diverse microbiota.4 More research is needed to determine pathogenesis, but current data support that the gut environment can impact metabolism, which can positively or negatively affect immunity.27

Allergic Rhinitis
Nearly one-third of the US population is affected by allergic rhinitis. Several probiotic strains are associated with its prevention and treatment, including Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus johnsonii EM1, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus paracasei, and Bifidobacterium lactis NCC2818.3

A combination of a Lactobacillus strain and a Bifidobacterium strain has been shown to be most effective at decreasing the intensity and duration of symptoms. This could lead to a decreased use of medication as treatment.3,29 Selecting a probiotic strain and dosage is something best done under a clinician’s supervision.

Atopic Dermatitis
Ten percent to 20% of children and 1% to 3% of adults suffer from the chronic inflammatory skin disease atopic dermatitis. This condition occurs when a genetically predisposed individual experiences an instantaneous reaction to an environmental or food antigen that stimulates an immune response. Youth with atopic dermatitis tend to have less bifidobacteria present in their microbiota, and a less diverse colony of microflora overall.4

Supplementation with Lactobacillus strains and strains of Lactobacillus with Bifidobacterium (especially B animalis subsp. lactis BB-12) has been shown to help prevent atopic dermatitis development in both at-risk and general populations.3,32 This benefit was seen most clearly in one trial examined in a 2015 meta-analysis in which participants were women in the pre- and postnatal periods.32

Several strains of Lactobacillus have been studied (L paracasei, Lactobacillus salivarius, and Lactobacillus fermentum) with positive results.3 One double-blinded, prospective, randomized placebo-controlled trial evaluated the effects of L paracasei, L fermentum, and a combination of both strains on quality or life, disease severity, and immune response in youth with atopic dermatitis. Participants comprised 220 children, aged 1 to 18, who presented with moderate to severe atopic dermatitis. Both individual strains of Lactobacillus supplementation and the combined strain supplement proved to be significantly effective at decreasing disease severity. This was especially notable in subjects younger than 12 who had been breast-fed for a minimum of six months. Quality-of-life scores also improved in all supplemented groups compared with placebo, but not significantly.33

Probiotics in Pregnancy and Youth
Consuming probiotic foods or supplements may have benefits throughout the lifespan, whether passed from a mother to a fetus or directly consumed by a baby or a child. A systematic review studying safety and efficacy of probiotic use during pregnancy noted no mortality or serious adverse events in this population, and consumption is considered safe.13

Pre- and Postnatal Periods
Allergic risk and response begin before birth, as the mother’s gut microbiota composition influences her fetus’ via the placenta and amniotic fluid.29 Method of birth and infant feeding choices also influence the formation of the microbiome, with vaginal birth and breast-feeding providing the greatest protection, particularly against atopic dermatitis.21,29 Some researchers consider the perinatal period to be the most influential period for probiotic utilization and allergy prevention.4

Infancy
Supplementing with FOS or GOS may help prevent atopic dermatitis in infants, particularly when added to cow’s milk–based formula as a 9:1 ratio of GOS to FOS.2 Breast-fed infants show higher concentrations and different strains of bifidobacteria than formula-fed infants; this could be protective against the eventual development of allergies.29

A systemic review of randomized controlled trials and a controlled cohort study found that consistency in probiotic consumption was key to decreasing the development of atopic dermatitis. More specifically, the use of probiotic supplements in Asia and Europe in the pre- and postnatal periods prevented atopic dermatitis from developing in babies and children. Atopic dermatitis also was less likely to occur in infants if probiotic supplements were dispensed in the first six months of life; waiting until the child was older than 12 months didn’t produce this same response.21

Conversely, several randomized, double-blinded, placebo-controlled trials studied the effects of both a maternal and an infant probiotic supplement of different strains of L rhamnosus on atopic dermatitis development with a different result. Infant supplementation of L rhamnosus GG began within the first six months of life with the goal of reducing atopic dermatitis development in high-risk children by age 2. Infants received 10 billion CFU of L rhamnosus GG and 225 mg of inulin daily if they were in the probiotics group, or 325 mg of inulin alone if they were in the placebo group. When the subjects turned 2, 30.9% of the placebo group and 28.7% of the probiotic group presented with atopic dermatitis.21

The maternal supplementation study evaluated pregnant women who received a probiotic supplement of L rhamnosus HN001 daily from the beginning of the second trimester to six months postpartum (only if breast-feeding). The incidence of atopic dermatitis was similar to the previous infant supplementation study, with the probiotic group reporting an 18% incidence of atopic dermatitis and the placebo group 21.5%.21

Pediatrics
The immune system continues to grow and form in early childhood, with regular bacterial exposure a benefit in developing a robust microbiome.29 Whether regular probiotic supplementation is warranted remains unknown as researchers seek to determine appropriate strains, dosages, and duration of use.

A group of more than 800 children aged 5 to 10 were evaluated via a parental questionnaire regarding the development of allergies; all were considered at high risk f allergy development due to genetic or environmental factors. Children who had received probiotic supplements as infants had a slightly higher risk (36.5% vs 29%) of developing allergic rhino-conjunctivitis, an inflammatory reaction that presents in both eyes and nose (as opposed to rhinitis, which mainly affects the nose), than those who didn’t receive the supplements.21

Probiotic Safety and Efficacy
After reviewing more than 600 studies, the US Department of Health and Human Services issued a statement that probiotics generally were well tolerated and that their side effects likely don’t outweigh the risk of usage.8 The most common side effects include systemic infection, metabolic malfunction, an overactive immune response, and gene transfer. These side effects are most common in individuals with a suppressed immune response.12

Adverse events of probiotic consumption often aren’t reported or noted as statistically significant, making it difficult to determine their prevalence. Assessing potential risk by conducting a large, diverse population study may yield better insight into previously unreported adverse reactions.12 Vulnerable groups that may require further study include pregnant women, infants, and immunocompromised individuals.4

Continued research should evaluate probiotic content and viability in products that claim to contain them to help ensure potential benefits are being conferred. Probiotic viability can be impacted by different food additives, available oxygen, microbes, and storage conditions. Therefore, points of analysis should include the effects of environmental stressors on probiotics and acid and oxygen levels, as well as what strains to include in products to maximize efficacy.8

For their part, supplement manufacturers must contend with not only sourcing and dosing but also utilizing tenable and cost-effective processes.1 It can be difficult to safely and adequately isolate appropriate bacteria strains in a concentration high enough to yield benefits. Companies must make continued efforts to hone this process and develop palatable probiotic-containing foods and supplements.1,12

Knowledge Among Health Care Professionals
In a study of 1,066 health care professionals’ knowledge of different strains, usage, and appropriate dosage of probiotics, respondents demonstrated a “medium” level of understanding. The most commonly known species of probiotics were L acidophilus (92%), Bifidobacterium bifidum (82%), and L rhamnosus (62%). Sixty percent of surveyed clinicians, who included pharmacists, dentists, midwives, doctors, and allied health professionals, reported they believed probiotics were helpful in combating allergies.

In a separate survey of more than 1,500 health care practitioners, 91% of dietitians reported they would recommend them to their patients and RDs were considered to have the best working knowledge of probiotics.9

Study Limitations
Much research has been conducted on probiotic supplementation, with inconclusive results. Many studies show an association between probiotic consumption and lack of allergic response, but dosage and duration of treatment with specific strains often are inconsistent or limited, which makes it difficult for clinicians to adapt the trial results into practical recommendations for their patients.24

Far fewer studies have examined the variety of naturally occurring probiotics in foods such as kefir or kimchi. Though dietary sources of probiotics may be a challenge to study, many different cultures and dietary patterns already incorporate food sources of both pre- and probiotics. Large, randomized, double-blinded, placebo-controlled trials involving probiotic-containing foods can assess their efficacy and potentially result in populationwide recommendations. A broader understanding of the diversity of an individual’s microflora before probiotic introduction also could be useful to better determine the most effective and efficient supplemental strains.4

Putting It Into Practice
Probiotics have long been associated with a flourishing and diverse gut microbiota and favorable immune response. Recent research has been instrumental in illustrating how probiotic-containing foods and supplements also may aid in preventing or treating allergenic responses throughout the lifespan. Dietitians can familiarize themselves with various strains, doses, formularies, and sources to ensure that maximum benefits are delivered to their clients.

Dietitians can use nutrition education to introduce patients to probiotic-containing foods such as fermented foods like kimchi and sauerkraut and dairy products like Greek yogurt and kefir.34 They also can help clients determine the most appropriate strains and products and how to best incorporate probiotics into their diet.35

Currently, there isn’t a global recommendation for standardized probiotic use as a primary form of allergy prevention, largely due to unanswered research questions.21 Clients can explore accessible, sustainable, and affordable sources of probiotics under a health care provider’s supervision, but more well-structured, long-term research is needed to truly understand their potential benefits and long-term effects.

— Alexandria Hardy, RDN, LDN, is a consultant in corporate wellness and a freelance food and nutrition writer based in Pennsylvania.

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Differentiate between pre-, pro-, and synbiotics.
2. Distinguish three dietary sources of probiotics to prevent or treat allergies.
3. Explain how maternal use of probiotics can improve peri- and postnatal allergy outcomes.
4. Assess the most common gut bacterial phyla and genera and describe how they impact the intestinal microflora.

CPE Monthly Examination

1. What is the primary function of a probiotic?
a. To improve the immune system
b. To diversify the intestinal flora
c. To promote weight maintenance
d. To improve digestion

2. Which of the following foods contains prebiotics?
a. Milk
b. Rice
c. Garlic
d. Cabbage

3. Consuming Bifidobacterium animalis subsp. lactis BB-12 and Streptococcus thermophilus helped alleviate gastrointestinal symptoms in which type of food allergy?
a. Milk
b. Peanut
c. Egg
d. Legume

4. What two genera of probiotics have been shown to provide the most immune support?
a. Lactobacillus and Alistipes
b. Bifidobacterium and Parabacteroides
c. Clostridium and Enterococcus
d. Lactobacillus and Bifidobacterium

5. How does supplementation with Lactobacillus strains impact the development of atopic dermatitis?
a. No impact on development
b. Increases risk of development
c. Lowers risk of development
d. Increases age of development

6. What is the minimum probiotic level needed to potentially confer therapeutic benefits?
a. 10^4 colony-forming units (CFUs)/g of viable cells
b. 10^5 CFUs/g of viable cells
c. 10^6 CFUs/g of viable cells
d. 10^7 CFUs/g of viable cells

7. In what population are side effects from probiotic use most likely to occur?
a. Immunocompromised
b. Children
c. Older adults
d. Pregnant women

8. What is one of the biggest barriers regarding consumer probiotic intake?
a. Consistency
b. Cost
c. Source
d. Knowledge

9. What bacterial genera/phyla make up 90% of the microbiota?
a. Chloroflexi and Clostridium
b. Proteobacteria and Actinobacteria
c. Verrucomicrobia and Fusobacteria
d. Firmicutes and Bacteroidetes

10. What can impact a probiotic strain’s viability?
a. Acidity and alkalinity
b. Sustainability
c. Oxygen exposure
d. Fortification
 

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