Category: Allergies

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Certain Gut Bacteria Assist in Immunotherapy for Milk Allergy

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Researchers in Japan have discovered a link between gut bacteria and the success of milk-allergy oral immunotherapy. Published in the scientific journal Allergology International, the study found that Bifidobacterium – a genus of beneficial bacteria in the gut – was associated with a higher chance of successful treatment. The finding may help in the development of more effective oral immunotherapies, perhaps by combining them with probiotic supplements.

Many children have allergic reactions to certain milk proteins. Most grow out of it but some have to contend with lifelong allergy. Milk allergy can be improved by oral immunotherapy – taking small, increasing doses of milk. Unfortunately, while allergic reactions are controlled during treatment, in most cases, tolerance disappears soon after the treatment ends.

Gut bacteria are thought to help reduce allergic reactions to some foods, but little is known about the link between these bacteria and oral immunotherapy for milk allergy. Hiroshi Ohno led a team at the RIKEN Center for Integrative Medical Sciences to find out why. The researchers examined 32 children with cow’s milk allergy who received oral immunotherapy, with the first month being conducted in a hospital. “Oral immunotherapy is not without risk,” explains Ohno. “We closely monitored the children in the hospital, and in fact 4 children had such severe reactions to the milk that we could not allow them to continue the treatment.”

The remaining 28 children then completed an additional 12 months of treatment at home. Next, they avoided milk for two weeks, and were then tested on a double-blind, placebo-controlled food challenge to see if they could still tolerate milk without any allergic reactions. During the food challenge, children were initially given a tiny amount of placebo or milk (only 0.01mL) which was gradually increased every 20 minutes until they had an allergic reaction or until they could drink the final 30mL without a reaction.

The researchers focused their analyses on immunological and bacterial changes during the treatment and the relationship between gut bacteria and successful treatment—which was defined as showing milk tolerance that lasted beyond the treatment period by passing the food challenge. They found that during treatment, immunological markers for cow’s milk allergy improved, and bacteria in the gut changed. Nevertheless, after two weeks of avoiding milk, only 7 of the 28 children passed the food challenge, even though they had been able to drink milk safely at the end of the treatment.

To understand why the treatment worked for these seven children but not the others, the team looked for the clinical factors and types of gut bacteria that were related to successful treatment. Of the clinical factors, unsuccessful treatment was more likely in children who were being treated for eczema or asthma and in children who initially had higher levels of milk-protein antibodies. Among the gut bacteria, the presence of Bifidobacterium, a genus of beneficial bacteria in the Bifidobacteriaceae family was related to a higher chance of successful treatment. In fact, only children who passed the final food challenge showed an increasing trend in these bacteria over the course of treatment. When considering ways to improve oral immunotherapy, this is good news because while the first two factors are difficult to change, the types of bacteria in one’s gut are not set in stone.

“With this study, we have identified gut environmental factors that help establish immune tolerance against cow’s milk allergy via oral immunotherapy,” says Ohno. “The next step is to examine the mechanisms underlying this phenomenon and to develop ways to improve the effectiveness of oral immunotherapy, such as the addition of probiotic supplements.”

Source: RIKEN

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Respiratory Allergies: Newly Discovered Inflammatory-triggering Molecule

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One of the molecules responsible for triggering the inflammation that causes allergic respiratory diseases, such as asthma and allergic rhinitis, has just been discovered by scientists in France. This molecule, from the alarmin family, represents a therapeutic target of major interest for the treatment of allergic diseases. The study is published in the Journal of Experimental Medicine on 10 April.

The inflammation process plays a crucial role in allergic respiratory diseases, such as asthma and allergic rhinitis. Although the pulmonary epithelium is recognised as a major player in the respiratory inflammation that causes these diseases, the underlying mechanisms are still poorly understood.

The research team, from the CNRS, Inserm and the Université Toulouse III – Paul Sabatier and co-directed by Corinne Cayrol and Jean-Philippe Girard, has identified one of the molecules responsible for triggering these allergic reactions,. This molecule from the alarmin family, named TL1A, is released by lung epithelium cells a few minutes after exposure to a mould-type allergen.

It cooperates with another alarmin, interleukin-33, to alert the immune system.

This double alarm signal stimulates the activity of immune cells, triggering a cascade of reactions responsible for allergic inflammation.

Alarmins, therefore, constitute major therapeutic targets for the treatment of respiratory allergic diseases. In a few years’ time, treatments based on antibodies blocking the TL1A alarmin could benefit patients suffering from severe asthma or other allergic diseases.

Source: CNRS

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Sublingual Immunotherapy for Food Allergies Safe and Effective for High-risk Children

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New research from the University of British Columbia reveals a safe path to overcoming food allergies for older children and others who can’t risk consuming allergens orally to build up their resistance. Sublingual immunotherapy (SLIT) involves placing smaller amounts of food allergens under the tongue.

A study conducted by UBC clinical professor and paediatric allergist Dr Edmond Chan and his team at BC Children’s Hospital Research Institute found SLIT to be as safe and effective for high-risk older children and adolescents as oral immunotherapy is for preschoolers.

The study was published in The Journal of Allergy and Clinical Immunology.

“Our work confirms the safety and effectiveness of SLIT for older children and adolescents with multiple food allergies at higher risk of severe reaction,” said Dr Chan. “These are patients for whom oral immunotherapy would typically be denied because it’s felt to be too risky, so this could be the best approach for that population.”

Previously published research from Dr Chan’s team has shown that preschool oral immunotherapy is safe and effective in the real world. The protocol involves a “build-up phase” of several months, when patients visit a clinic every two weeks to ingest a higher dose of an allergen under medical supervision before continuing the same daily dose between visits. When they reach a certain dose – usually around 300mg of protein – they enter a “maintenance phase” during which they take that target daily dose at home. After a year of maintenance doses, approximately four out of five patients are able to pass an oral challenge test in which they tolerate a much higher dose of 4000mg of protein.

However, the build-up phase is risky for older children and those with a history of severe reactions. Dr Chan’s group has been looking for a safer way to get this at-risk group of patients to the maintenance phase.

They recruited about 180 such patients between the ages of four and 18, most with multiple food allergies. The SLIT protocol (started when COVID-19 pandemic restrictions were in place) required patients to have virtually supervised appointments 3-5 times over several months to build up to a small dose – in most cases, just 2mg of protein – which is absorbed through the membranes under the tongue rather than swallowed and ingested.

The patients’ caregivers learned how to mix and administer these doses at home using novel recipes based on products you can buy at the grocery store, developed with the team’s research dietitian. A wide variety of allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens. Patients took these doses daily for 1–2 years.

“It takes up to twice as long as oral immunotherapy, but we wouldn’t have had it any other way, because we needed the superior safety of SLIT for these older kids that are felt to be more severe,” said Dr. Chan.

While most patients had mild symptoms during the build-up phase, none had severe reactions during either build-up or maintenance. Seventy per cent of those tested at the end of the protocol could tolerate 300mg of their allergen – a success rate nearly as high as that for oral immunotherapy.

The results were encouraging for a therapy that any family can undertake at home with guidance from professionals.

“Besides safety considerations in older children, allergists are often quite burdened by the oral immunotherapy build-up phase, where a patient may require 11 or more visits to the clinic. They just don’t feel they have the capacity to offer that many visits in their office,” said Dr Chan. “In our clinic, we are starting to do more home-based approaches because the demand for medical appointments that would allow supervision far outstrips the supply. We are trying to develop an approach, based on data, that matches a patient’s risk level with the appropriate amount of supervision. Our SLIT data suggests that home-based SLIT build-up is safe.”

Ultimately, the trial highlights an alternative that allergists should now consider for patients who cannot safely undertake oral immunotherapy. The trade-off for greater safety is simply a longer timeline, but it comes with the benefit of keeping clinics free for those who need them most.

Source: University of British Columbia

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Asthma Drug Omalizumab can Limit Allergic Reactions to Foods

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An existing biologic drug, omalizumab, can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.

The findings, published in the New England Journal of Medicine, suggest that regular use of omalizumab could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.

“I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies,” said the study’s senior author, Sharon Chinthrajah, MD, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine.

“Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”

Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.

All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.

Allergies are common

Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.

“Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.

In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitised to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it – but people often dislike foods they were long required to avoid.

“There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.

Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.

“We think it should have the same impact regardless of what food it is,” Chinthrajah said.

Injections stave off severe reactions

The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.

Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.

Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.

About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.

Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.

More questions

More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.

“We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”

The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.

Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.

The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.

The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”

Source: Stanford Medicine

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Measuring Grass Pollen Allergens instead of Pollen Count will Help Hay Fever Sufferers

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New research shows grass allergen levels are more consistently associated with hay fever symptoms than grass pollen counts.

The research, published in The Journal of Allergy and Clinical Immunology and led by King’s College London and Imperial College London, shows for the first time that measuring airborne allergen levels will help people with hay fever better control their symptoms.

In the UK, 1 in 4 adults suffer from hay fever from late-March to September. Symptoms include a runny or blocked nose, sneezing and coughing and itchy, red or watery eyes.

Hay fever can make lung conditions such as asthma worse, causing wheezing and breathing difficulties which can lead to hospitalisation.

Many people with hay fever monitor peak pollen times to manage their symptoms. In the UK (as well as South Africa), pollen grains are manually measured to find the daily pollen count.

But the study authors say measuring allergen levels instead will be more accurate as each pollen grain can release a different amount of allergen each day, and it is the allergens in the air that are primarily responsible for causing hay fever symptoms.

Currently, there is no regular monitoring of allergen levels in the UK or elsewhere.

Authors collected daily symptom and medication scores from adult participants in an allergy clinical trial as well as daily counts of asthma hospital admissions in London.

They measured grass pollen counts and but also sampled air for the grass pollen Phl p 5 grass allergen protein in the same location at King’s College London over the same time period.

First author Dr. Elaine Fuertes, from Imperial College London, said: “Grass pollen is the most common hay fever trigger. In this study, we measured grass allergen (Phl p 5) levels and found this was more consistently associated with allergic respiratory symptoms than grass pollen counts.”

Senior author Professor Stephen Till, from King’s College London, said: “High pollen season can be serious for people who suffer with hay fever, and can trigger severe asthma attacks in those who are allergic to grass pollen. This study shows there is a superior way of measuring pollen allergens in the air than the traditional pollen count. Monitoring grass allergen instead of grass pollen counts gives results that are more consistently linked to patients’ symptoms and could allow people with serious allergies to be better prepared during the pollen season.”

Research is ongoing to see whether regular measurement of allergen levels can become the standard in the UK, and whether there are other environmental factors, such as meteorological factors including temperature, wind, humidity, and air pollutants, that influence how much allergen each pollen grain releases.

Source: King’s College London

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Existing Allergy Medication Unleashes Antitumour Immunity against Lung Cancer

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Researchers from Mount Sinai report in Nature that they have identified an allergy pathway that, when blocked, unleashes antitumour immunity in mouse models of non-small cell lung cancer (NSCLC).

And in an early parallel study in humans, combining immunotherapy with dupilumab – an Interleukin-4 (IL-4) receptor-blocking antibody widely used for treating allergies and asthma – boosted patients’ immune systems, with one out of the six experiencing significant tumour reduction.

“Immunotherapy using checkpoint blockade has revolutionised treatment for non-small cell lung cancer, the most common form of lung cancer, but currently only about a third of patients respond to it alone, and in most patients, the benefit is temporary,” says senior study author Miriam Merad, MD, PhD, at the Icahn School of Medicine at Mount Sinai.

“A big focus of our program TARGET is to use single cell technology and artificial intelligence to identify molecular immune programs that can dampen tumour immune response to checkpoint blockade.”

Also known as a PD1 inhibitor, checkpoint blockade is a type of cancer immunotherapy that can unleash the cancer-killing activity of T cells.

“Using single cell technologies, we discovered that the immune cells infiltrating lung cancers, as well as other cancers we studied, exhibited characteristics of a ‘type 2’ immune response, which is commonly associated with allergic conditions like eczema and asthma,” says first study author Nelson LaMarche, PhD, a postdoctoral research fellow in the lab of Dr Merad.

“These results led us to explore whether we could repurpose a medication typically used for allergic conditions to ‘rescue’ or enhance tutor response to checkpoint blockade,” says Thomas Marron, MD, PhD, co-senior author of the study.

“Strikingly, we found that IL-4 blockade enhanced lung cancer response to checkpoint blockade in mice and in six lung cancer patients with treatment-resistant disease. In fact, one patient whose lung cancer was growing despite checkpoint blockade had nearly all their cancer disappear after receiving just three doses of the allergy medication, and his cancer remains controlled today, over 17 months later.”

The researchers are encouraged by the initial results but emphasise the need for larger clinical trials to validate the drug’s efficacy in treating NSCLC.

Beyond the clinical trial findings reported in the current Nature paper, the investigators have now expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients, and are starting to investigate its use in early-stage lung cancer as well. Through these trials, they are searching for biomarkers to identify those cancer patients who might benefit from dupilumab treatment.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

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Predicting and Preventing Anaphylaxis During Food Allergy Tests

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A team of University of Michigan researchers developed a method that measures water loss from the skin to predict anaphylaxis during oral food challenges before it becomes clinically evident. The results are published in The Journal of Clinical Investigation.

Oral food challenges – when a patient ingests increasing doses up to a full serving of the suspected food allergen under supervision of a medical provider – are the diagnostic standard as skin and blood allergy tests have high false positive rates.

Although a highly accurate diagnostic test, patients often experience anaphylaxis during oral food challenges necessitating an epinephrine injection.

“This method could enhance the ability to detect and predict anaphylaxis during oral food challenges prior to the need for epinephrine, greatly improving patient safety and comfort,” said Charles Schuler, M.D., lead author of the study and an immunologist at Michigan Medicine.

Building on existing research

During anaphylaxis, the dilation or widening of the blood vessels increases heat and water loss from the surface of the skin.

Previous research has assessed facial thermography, which uses a specialized camera to detect heat patterns emitted from the skin, as a method to predict anaphylaxis.

However, this method requires optics expertise, tightly controlled conditions and for the patient to sit still for an extended period – making this an impractical choice, especially for assessing food allergies in children.

The researchers validated the use of transepidermal water loss, a measurement that represents the amount of water that escapes from a given skin area per hour, by comparing its ability to detect anaphylaxis with biochemical and clinical observation methods.

They found that transepidermal water loss increases during food allergy reactions and anaphylaxis.

The rise in skin water loss correlated with biochemical markers of anaphylaxis and substantially preceded clinical detection of anaphylaxis.

“Transepidermal water loss measurement can be done in office without specialized equipment, affixed to the skin and works in children making it a vast improvement from previous attempts at early anaphylaxis detection methods,” said Schuler.

Schuler’s research group is currently recruiting participants aged six months to five years old for a pilot clinical trial, Predicting Peanut Anaphylaxis and Reducing Epinephrine, that monitors transepidermal water loss from the forearm during a peanut allergy food challenge.

Results will help pinpoint values associated with anaphylaxis to determine “stopping rules” to end oral food challenges, hopefully reducing the need for epinephrine injections.

Source: Michigan Medicine – University of Michigan

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Pre-existing Allergies Increase Risk of Experiencing Long COVID Symptoms

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In an analysis of published prospective studies of people of all ages with confirmed SARS-CoV-2 infection who were followed for at least 12 months, pre-existing allergic conditions were linked to higher risks of experiencing long-term symptoms associated with COVID, or ‘Long COVID’.  

The analysis, which is published in Clinical & Experimental Allergy, identified 13 relevant studies (with a total of 9 967 participants) published between January 1, 2020 and January 19, 2023.

Although the data as a whole from the studies suggested that individuals with asthma or rhinitis might be at increased risk of long COVID after SARS-CoV-2 infection, the evidence for these associations was very uncertain. Therefore, more robust epidemiological research is needed to clarify the role of allergy in the development of Long COVID.

“We need a better, harmonised definition of what is considered Long COVID for epidemiological studies of this sort. Regardless we will be updating our analysis once further studies have been published in the next few months,” said corresponding author Christian Apfelbacher, PhD, of the Institute of Social Medicine and Health Systems Research, in Germany.

Source: Wiley

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Sublingual Immunotherapy for Peanut-Allergic Toddlers is Safer and More Effective

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A three-year clinical trial has shown that the sublingual immunotherapy (SLIT) is safe in peanut-allergic children ages one to four, with a greater likelihood of desensitisation and remission the earlier the treatment began. SLIT approach where the treatment is given as a small amount of liquid under the tongue, instead of peanut flour that is mixed with other food and then eaten like it is during oral immunotherapy, or OIT.

Published in the Journal of Allergy and Clinical Immunology, this is the first randomised, controlled trial to investigate – in this young age group – the efficacy and feasibility of SLIT.

The study included 50 peanut-allergic children between the ages of one and four, randomised to receive 4mg peanut SLIT versus placebo. Participants were randomised 1:1 to receive either peanut SLIT or placebo. Desensitization to peanut was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after three years of treatment.

Findings showed that peanut SLIT can be highly effective in treating peanut-allergic toddlers with almost 80% tolerating 15 peanuts without allergic symptoms after completing the treatment. With most typical peanut-allergic reactions being caused by one peanut or less, these results would translate into strong protection against exposures to peanut. In addition, researchers showed that remission of the peanut allergy may be possible after peanut SLIT with 63% of the toddlers maintaining their protection three months after stopping the treatment. These new findings show that early intervention with peanut SLIT is promising and warrants further development.

Led by Edwin Kim, MD, associate professor of paediatrics at the UNC School of Medicine, said: “From our prior studies in older children, we were optimistic that peanut SLIT could have a similar treatment effect in toddlers.

“However, what we found was even better. The desensitisation levels we saw were higher than expected and on par with levels we normally would only expect with oral immunotherapy. Just as important, rather than wearing off quickly, we were excited to see that over 60% stayed protected three months after stopping the treatment.”

One of the presumed strengths of the SLIT approach when compared to OIT has been its overall safety and simple administration. While most treatment side effects with OIT are mild to moderate, severe reactions requiring emergency treatment do occur and there remains a critical need to develop treatments with more manageable side effects.

“Peanut OIT is currently available and being offered by increasing numbers of allergists, however we are quickly learning that in addition to its known risk of allergic reactions, the actual doing of OIT can be very difficult for many families,” said Kim. “Peanut SLIT could be a good option to consider as it may be able to provide comparable levels of protection while being safe and easier to administer.”

Compared to OIT, the SLIT approach is likely to be a safer option, Kim said, with the most common side effect consisting of oral itching. Treatments that can protect children from allergic reactions while still being safe and practical for busy families can be life-changing, and researchers are hopeful that peanut SLIT can be one of those options.

“Even with the push to introduce peanut in early childhood in order to prevent the allergy, peanut allergy remains one of the most common food allergies,” said Kim. “A result of early peanut introduction is that we are diagnosing peanut allergy at younger and younger ages making it vitally important to develop treatments that can be safe and effective at preventing allergic reactions in these young children.”

Source: UNC School of Medicine

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Does the ‘Hygiene Hypothesis’ Still Hold Water?

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Over the last few decades, there has been growing popularity for the ‘hygiene hypothesis’, which suggests that some level of microbial exposure helps protects against developing allergy. Now, an article published in Science Immunology by researchers from Karolinska Institutet challenges this hypothesis by showing that mice with high infectious exposures from birth have the same, if not an even greater ability to develop allergic immune responses than ‘clean’ laboratory mice.

Studies have suggested that certain infections might reduce the production of inflammatory antibodies to allergens and alter the behaviour of T cells involved in allergies. It has also been suggested that ‘good’ intestinal bacteria could shut off inflammation elsewhere in the body.

Robust allergic responses

Researchers have now compared the allergic immune response in ‘dirty’ wildling mice to those of typical clean laboratory mice. They found very little evidence that the antibody response was altered or that the function of T cells changed in a meaningful way. Nor did anti-inflammatory responses evoked by good gut bacteria appear to be capable of switching off the allergic immune response. On the contrary, wildling mice developed robust signs of pathological inflammation and allergic responses when exposed to allergens.

“This was a little unexpected but suggests that it’s not as simple as saying, ‘dirty lifestyles will stop allergies while clean lifestyles may set them off’. There are probably very specific contexts where this is true, but it is perhaps not a general rule,” says Jonathan Coquet, co-author of the study and Associate Professor at Karolinska Institutet.

More like the human immune system

The wildling mice are genetically identical to clean laboratory mice but are housed under ‘semi-natural’ conditions and have rich microbial exposures from birth.

“The immune systems of wildling mice better represent the human immune system and so we hope that they can bring us closer to the truth of how microbes act upon the body,” says Jonathan Coquet.

The findings contribute to the general understanding of how allergies may arise and may also have clinical implications. Using experimental infections to treat patients suffering from inflammatory diseases has also been attempted in recent clinical trials. For example, infecting people with worms or performing faecal transplantations has been proposed as a tool to combat inflammatory diseases. Newborns delivered through C-section, have had maternal faecal transplantation and bacterial supplementation with the aim of promoting good bacteria in the baby’s gut and the child’s future health.

Beneficial effects of exposure not clear as we’d like

“This field of research can provide important insights into how infections and microbes can be used to facilitate health, but it is still in its infancy. Our study is a reminder that general and broad exposures to microbes may not have the clear beneficial effects that we wish them to have,” says Susanne Nylén, co-author of the study and Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

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