Kate Johnson

February 23, 2015

HOUSTON — The type and mix of gut bacteria during the first 6 months of an infant's life has a profound influence on the developing immune system and on the risk for allergies and asthma, according to new research.

"We are really developing what we think is a new model for atopy," said investigator Susan Lynch, PhD, from the University of California, San Francisco, who is a member of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) research team.

In fact, manipulating an infant's "dysfunctional" microbiome might soon be a therapeutic approach, according to several experts who spoke during a plenary session here at the American Academy of Allergy, Asthma & Immunology 2015.

"We think the potential for therapy is really in the very early stages of life, when the microbiome is most plastic," Dr Lynch explained. "This is where we could most dramatically influence this critical period of immune maturation."

We think the potential for therapy is really in the very early stages of life, when the microbiome is most plastic.

"I think this is the future of our specialty; maybe not in the next 5 years, but certainly in 10 years," said session moderator Karin Pacheco, MD, from the Colorado School of Public Health in Denver. "I think we will learn how to manipulate the microbial environment to achieve the health and absence of disease — certainly allergic disease — that we're looking for."

During the session, presenters discussed a series of six studies from the WHEALS team in which stool and blood samples from 298 children younger than 12 months were evaluated.

The investigators found that factors such as breastfeeding, mode of birth, and pet exposure, which have been known to affect allergy and asthma, do so by influencing the infant microbiome. In turn, the microbiome affects the development of regulatory T-cells, immunoglobulin E responsiveness, and the development of allergy and asthma symptoms.

One of the series was the first human study to show an association between microbial richness, diversity, and evenness in the infant gut and regulatory T-cell development, all of which help keep allergies in check.

Another showed that bacteria were phylogenetically diverse in the microbiomes of breast-fed babies, whereas in babies who were not breast-fed, the microbiomes were dominated by Lachnospiraceae.

In a study that expanded on this finding, investigators determined that the breast-fed babies, who had low levels of Lachnospiraceae bacteria, were less likely to have pet allergy than babies who were not breast-fed.

The other studies in the series showed how mode of birth and maternal smoking, marital status, and gestational age affect the infant microbiome; how the microbiome can affect nocturnal asthma symptoms; and how response to tetanus toxoid immunization is altered by an infant's microbiome.

"It's the child's microbiome that ties it all together," said WHEALS investigator Christine Cole Johnson, PhD, from the Henry Ford Hospital in Detroit. "And we're finding that environmental, lifestyle, and medical characteristics affect that microbiome."

"Things we thought were related to the risk of allergy and asthma are always related to the development of the gut microbiome," added Dennis Ownby, MD, a WHEALS investigator from Georgia Regents Health System in Augusta, Georgia.

The next step will be to determine how to recognize microbiome abnormalities, who to test for them, and how to treat them.

"From a very early stage in life, there are signatures of dysbiotic microbiome composition and dysfunctional microbiomes in the guts of infants who are at much higher risk of developing atopy," Dr Lynch said during a press conference.

"It's probably a little premature to say that we will have a cure, or even a management strategy, based on these data at the outset," she told Medscape Medical News. However, research from her group is already showing that mice given supplements of a probiotic called Lactobacillus johnsonii experience airway protection against allergen challenge, and even against viral respiratory infection.

"I think we are on the verge of seeing [microbiome-related] treatments in humans," said Joseph Petrosino, PhD, from the Alkek Center for Metagenomics and Microbiome at the Baylor College of Medicine in Houston.

"Trials are underway in which the mother's microbiota is being introduced to infants shortly after cesarean birth in an attempt to colonize the baby with the organisms he or she wasn't exposed to during delivery," he told Medscape Medical News.

"However, I think we have only scratched the surface with regard to the impact of microbial and environmental exposures during pregnancy and shortly after birth," he explained.

"These studies are focused on allergies and asthma, but I believe further research will find that other immune-related disorders, such as type 1 diabetes and celiac disease, are also influenced, at least in part, by such exposures," said Dr Petrosino. "Further, these impacts may not be exclusive to diseases thought to involve the immune response, but also may relate to the development of other organs and systems in the body."

Dr Lynch, Dr Pacheco, Dr Cole Johnson, Dr Ownby, Dr Gallo, and Dr Petrosino have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2015: Abstract 327, presented February 21, 2015; abstracts 503, 504, 548, presented February 22, 2015; abstracts 888, 889, to be presented February 24, 2015.


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