Newborn gut microbiome predicts later allergy and asthma

 

Numerous studies in recent years have tied early exposure to beneficial microbes in the environment to a host of positive health effects. Breastfeeding, vaginal births (as opposed to C-sections) and even having dogs in the household during the first year of life are all associated with protective effects against allergies and asthma. Recently, researchers at the University of British Columbia reported that three-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.

The new paper, published in Nature Medicine, links a particular pattern of microbes in the guts of one-month-old infants to a three-fold higher risk of developing allergic reactions by age two and asthma by age four.

The paper demonstrates that the perturbed 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 surmise that having fewer of these cells leads to a hyperactive immune system and eventually to chronic asthmatic inflammation of the lungs.

"Currently, children are typically six or seven 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 reengineer the community of microbes in at-risk infants to prevent allergic asthma from developing?" said the senior author.

As part of this study, the team collected stool samples from the diapers of the infants and kept them on ice. They used high-throughput genetic analysis of the stool samples to map the gut microbes of 130 young infants around one-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 smallest of these three groups (11 of 130 infants) were three times more likely to develop atopy and asthma than the rest of the infants. The size of this at-risk group was strikingly consistent with the rate of allergic asthma in the general population and the microbial diversity analysis showed that these infants were missing certain normal gut bacteria and also that they possessed abnormally high levels of certain resident fungal species[2].

To learn how the abnormal complement of gut microbes in these high-risk infants might cause the hypersensitive immune reactions that characterize atopy and asthma, the team studied the microbes' metabolic byproducts -- molecules in the stool samples that could offer clues about what these microbes had been up to in the gut.

They discovered that the guts of neonates with healthy microbiomes contained a wide range of molecules that can reduce inflammation. These include a set of fat molecules, or lipids, that the researchers suspect nourish immune cells called T-regulatory cells, whose job is to keep the rest of the immune system in check.

In contrast, these key anti-inflammatory lipids were absent in the guts of at-risk babies. Instead, the researchers detected different fats, including one associated with asthma in adults, called "12, 13 DIHOME." Further experiments found that even healthy, adult immune cells became hyper-sensitized after being exposed to just the byproducts of the at-risk babies' gut microbiomes, and that 12, 13 DIHOME in particular could reduce the number of 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 pro-inflammatory molecules end up in the gut.

The researchers 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 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.

The group also published a second paper in the journal Scientific Reports, detailing for the first time how numerous socioeconomic, environmental and demographic factors intersect to influence microbiome composition in the WHEALS children, without reference to particular disease risk factors. The researchers hope the findings of these two papers will spur development of tests to detect signs of an unhealthy gut microbiome in infants and to implement early-life interventions to shift microbial ecosystems towards a healthier state.

https://www.ucsf.edu/news/2016/09/404071/newborn-gut-microbiome-predicts-later-allergy-and-asthma-study-finds

Edited September 15th 2016