Our digestive tracts are home to trillions of microbes—including bacteria, fungi, and viruses. This microbial community, known as the microbiota, plays a role in illness and health. Scientists have suspected that infants’ gut microbiota could influence how their immune systems develop. A team led by Drs. Christine C. Johnson at the Henry Ford Health System in Detroit and Susan V. Lynch at the University of California, San Francisco, set out to examine the relationship between an infant’s gut microbiota and subsequent development of allergy and asthma. The study was funded by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). Results appeared online on September 12, 2016 in Nature Medicine.
The researchers analyzed stool samples from almost 300 infants, ages 1 to 11 months. The infants were part of a large, diverse study group born in and around Detroit between 2003 and 2007. The children and their families were followed over time to better understand how early-life exposure to environmental factors might affect the risk for allergy and asthma.
To determine the composition of gut microbes in the stool samples, the scientists examined sequence variation within ribosomal RNA (rRNA), a central component of the protein-manufacturing machinery of all living cells. The investigators found that the infants formed 3 groups characterized by distinct bacterial and fungal gut microbiota. Blood samples obtained from the infants at 2 years of age were tested for sensitivity to allergens. The researchers found that the 3 microbiota groups had substantially different risks for allergen sensitivity. The “high-risk” group had a relatively lower abundance of certain bacteria (such as Bifidobacterium, Akkermansia, and Faecalibacterium) and a higher level of some fungi (such as Candida and Rhodotorula). This high-risk microbiota group was also more likely to be diagnosed with asthma at 4 years of age. The relationship between gut microbiota and allergy and asthma held when the researchers controlled for other factors associated with allergic disease, such as breast feeding and dog allergens in the home.
The team analyzed metabolites in some of the infant’s stool samples. They found extensive differences among the 3 groups. Notably, the high-risk group had greater levels of metabolites that promote inflammation.
The scientists next exposed immune cells from healthy adults to metabolites extracted from the infant’s stool samples. The high-risk group’s samples increased the proportion of allergy-promoting immune cells and production of interleukin-4, an allergy-associated cell-signaling protein. These samples also reduced T-regulatory cells, a key group of immune cells necessary to prevent allergic responses. The team identified a lipid found at high levels in the highest risk group, called 12,13-DiHOME, that could suppress T-regulatory cells.
“We have been working for over a decade trying to figure out why some children get asthma and allergies and some don’t,” Johnson says. “It seems that the microbial communities within the body could be the keystone to understanding this and a number of different immune diseases.” “Humans have co-evolved with microbes, and as a result we rely on their genomes for a range of critical functions. Understanding the basis of human-microbial development may prove critical to unraveling the basis of allergy and asthma and to developing preventative therapeutic strategies,” Lynch adds.
Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, Panzer AR, LaMere B, Rackaityte E, Lukacs NW, Wegienka G, Boushey HA, Ownby DR, Zoratti EM, Levin AM, Johnson CC, Lynch SV. Nat Med. 2016 Sep 12. doi: 10.1038/nm.4176. [Epub ahead of print]. PMID: 27618652.
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