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September 13, 2016

Gut Microbiome at Birth Is Predictor of Allergies and Asthma in Later Years

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    A new study found that microbes living in a baby's gut during its first month of life may directly impact the developing immune system, leading to a higher risk of allergies and asthma later in childhood. [NIH]

    The impact of the gut microbiome on future health outcomes, especially in newborns, has been a controversial topic over the past several years, with scientists uncovering conflicting data about the microbial communities’ prognostic abilities. However now, a new study by researchers at the University of California, San Francisco (UCSF) and the Henry Ford Health System in Detroit, highlights the importance of developing early interventions to improve microbial health in young infants. The investigators believe that the microbes living in a baby's gut during its first month of life may directly impact the developing immune system, leading to a higher risk of allergies and asthma later in childhood.

    The research team was able to link a particular pattern of microbes in the guts of 1-month-old infants to a three-fold higher risk of developing allergic reactions by age 2 and asthma by age 4. The paper demonstrates that the disturbed microbial ecosystem present in these at-risk babies produces molecules that reduce the abundance of a key type of immune cell known to help prevent allergy. The researchers surmised that having fewer of these cells leads to a hyperactive immune system and eventually to chronic asthmatic inflammation of the lungs.

    "If we are to prevent disease development, we need to intervene early," explained co-senior study author Susan Lynch, Ph.D., associate professor of medicine at UCSF. "Currently, children are typically 6 or 7 years old when they are diagnosed with asthma, which has no cure and has to be managed through medication. But if the genesis of the disease is visible as a disruption of gut microbiota in the very earliest stages of postnatal life, it raises an exciting question: Could we re-engineer the community of microbes in at-risk infants to prevent allergic asthma from developing?"

    In recent years, some studies have tied early exposure to beneficial bacteria in the environment to a host of positive health effects. Breastfeeding, vaginal births (as opposed to cesarean sections), and even having dogs in the household during the first year of life are all associated with protective effects against allergies and asthma. Recent studies have reported that 3-month-old infants with low levels of four key types of gut bacteria were significantly more likely to show early-warning signs of asthma at their first birthdays than infants with normal levels of these bugs.

    "We have been working for over a decade, trying to figure out why some children get asthma and allergies and some don't," noted co-senior study author Christine Cole Johnson, Ph.D., M.P.H., chair of public health sciences in the Henry Ford Health System. "It seems that the microbial communities within the body could be the keystone to understanding this and a number of different immune diseases."

    Since 2003, Dr. Johnson's lab has been tracking a variety of early-life risk factors for asthma in a racially and socioeconomically diverse population of infants born in and around Detroit. The researchers conducted repeated follow-up appointments during the first year of life, and then tested the infants for allergies at the age of 2 and for asthma around their fourth birthdays.

    As part of this study, Dr. Johnson's team collected stool samples from the diapers of the infants and kept them on ice. Years later, Dr. Johnson connected with Dr. Lynch, whose lab specializes in human microbiome research, and the two researchers teamed up to discover how soon after birth they could detect microbiome differences predictive of asthma later in life and why these microbes were so influential in triggering the disease.

    "We went back to the freezers and pulled out the stool samples and shipped them over to UCSF, where the Lynch lab was able to use new genetic technology to examine them for the entire microbial community that had been there in these infants," Dr. Johnson remarked. "Technology has really changed—you couldn't have done that 10 years ago."

    Using high-throughput genetic analysis of the stool samples, the UCSF team was able to map the gut microbes of 130 young infants around 1 month of age—so-called neonates. This analysis, which was the first study of both bacterial and fungal diversity in the neonatal gut, found that the babies fell into one of three distinct groups, each characterized by different types of bacterial and fungal species in the gut.

    The findings from this study were published recently in Nature Medicine in an article entitled “Neonatal Gut Microbiota Associates with Childhood Multisensitized Atopy and T Cell Differentiation.”

    On the basis of the Henry Ford team's 2-year and 4-year follow-up data, the smallest of these three groups (11 of 130 infants) was three times more likely to develop atopy and asthma than the rest of the infants. The researchers noted that the size of this at-risk group was strikingly consistent with the rate of allergic asthma in the general population. Moreover, the research teams discovered that the guts of neonates with healthy microbiomes contained a wide range of molecules that can reduce inflammation. These include a set of lipids that the researchers suspect nourish immune cells called T-regulatory cells.

    The researchers suspect that gut microbes play a key role in processing dietary components such as fats, giving them a powerful influence over whether anti-inflammatory or proinflammatory molecules end up in the gut.

    Interestingly, the investigators also examined a number of environmental and socioeconomic factors to learn why some children developed a high-risk gut microbiome profile, but only found a couple of strong links: namely that male infants were more likely to have the problem than females, and also that those who didn't have dogs in the home were also more at risk, in line with the authors' earlier findings.

    "Humans have co-evolved with microbes, and, as a result, we rely on their genomes for certain critical functions. We believe this is particularly true during the earliest stages of human development," Dr. Lynch stated. "But lifestyles have changed dramatically over the past several decades: We've significantly reduced our exposure to these environmental microbes our bodies rely on. Having a dog track the external environment into the home may be just one way to improve the breadth of microbes babies are exposed to in very early life."

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