Many scientists have hypothesized that infants’ gut microbiota could influence the development of their immune system. Recently, a test led by Drs. Christine C. Johnson at the Henry Ford Health System in Detroit and Susan Lynch at the University of California, San Francisco, but this theory to test. Specifically, they set out to examine the relationship between an infant’s gut microbiota and their relative risk of atopy and asthma. The researchers inspected the composition of gut microbes in stool samples from almost 300 infants—all part of a diverse study group born in and around Detroit between 2003 and 2007—by means of examining sequence variation within ribosomal RNA. Ultimately, the team found that the infants could be divided into 3 separate groups, each with distinct bacterial and fungal gut microbiota.

When blood samples obtained from the infants at 2 years of age were tested for sensitivity to allergens, the 3 microbiota groups had significantly different risks for allergen sensitivity. The “high-risk” microbiota group had a relatively lower abundance of certain bacteria and a higher level of some fungi, and was more likely to be diagnosed with asthma at 4 years of age. This seeming link between gut microbiota and allergy and asthma was also manifested when other factors associated with allergic disease—such as breastfeeding—were controlled. Moreover, the researchers found that the high-risk group had a distinct set of metabolites that lacked anti-inflammatory fatty acids and breast milk-derived oligosaccharides that were found in children in the low-risk microbiota group, increasing vulnerability to inflammation.

Neonatal gut microbiota play a huge role in health and disease (Credit: Eric Atkins)

The researchers also mixed immune cells from healthy adult donors in solutions containing metabolites extracted from the infant’s stool samples. The high-risk group’s metabolite samples increased the amount of allergy-promoting immune cells interleukin-4, a cell-signaling protein associated with allergies, and also reduced T-regulatory cells, an essential group of immune cells that suppress allergic responses. This reduction in T-regulatory cells was also spurred by a lipid that the team identified, called 12,13-DiHOME, that was found at high levels in the high-risk group. Discussing this finding, Lynch expressed to The Scientist, “That for me is incredibly exciting as it suggests that microbial-associated metabolites in the neonatal gut may represent an important driver of early-life immune cell phenotypes associated with disease development in childhood.”

The team plans to conduct a similar study that will focus on environmental factors and how they may affect the development of the gut microbiota. According to Lynch, “Understanding the basis of human-microbial development may prove critical to unraveling the basis of allergy and asthma and to developing preventative therapeutic strategies.”