Early viral encounters may affect airway microbiota, lead to recurrent respiratory infections

Early viral encounters are associated with disadvantageous immune and microbiota profiles, as well as recurrent respiratory infections. A new study published in Nature Microbiology claims.

What is already known on this topic
Respiratory tract infections are responsible for 15% of deaths of children under the age of five. Although an altered development of the respiratory microbiota in early-life has been associated with higher susceptibility to respiratory tract infections, no longitudinal studies have investigated the cross-talk between the respiratory microbiota and the airway immune system in infants.

What this research adds
Researchers assessed viral infections and the airway microbiota of 114 healthy infants, from birth until they turned 12 months of age. Early viral infections co-occurred with stronger pro-inflammatory activity, which was associated with higher levels of Moraxella and Haemophilus bacteria, the team found. These microbial profiles were linked to an increased number of respiratory tract infections during the first year of life.

Conclusions
The findings suggest that early-life viral encounters could influence infants’ host-microbe cross-talk, leading to recurrent respiratory tract infections later in life.

Respiratory tract infections are responsible for 15% of deaths of children under the age of five. New research indicates that early viral encounters are associated with disadvantageous immune and microbiota profiles, as well as recurrent respiratory infections.

The findings, published in Nature Microbiology, suggest that early-life infections could influence infants’ host-microbe cross-talk, leading to respiratory infections later in life.

Scientists have known that the respiratory tract is colonized by a specialized microbiota during and immediately after birth. Although an altered development of the respiratory microbiota in early-life has been associated with higher susceptibility to respiratory tract infections, no longitudinal studies have investigated the cross-talk between the respiratory microbiota and the airway immune system in infants.

To address this question, Debby Bogaert at the University of Edinburgh and her colleagues set out to investigate gene expression dynamics in the airway mucosa and the presence of viral infections, as well as the development of the airway microbiota, in relation to respiratory tract infections during the first year of a person’s life.

Gene-expression dynamics

The team followed 114 healthy infants from birth until they turned 12 months of age. The study was part of the Microbiome Utrecht Infant Study, which collects data and samples at up to 11 time points over the first 12 months of life of participating infants.

First, the researchers tested samples of airway mucosa for genes with differential expression between subsequent time points. The largest number of differentially expressed genes was observed very early in life, between birth and 24 hours after birth.

Differentially expressed genes were mostly involved in immune pathways such as Toll-like receptor signaling and inflammasome signaling. Toll-like receptors are proteins that play a key role in the innate immune system, and inflammasomes are receptors that induce inflammation in response to microbes, among other things.

Next, the researchers grouped genes with similar expression patterns, which tend to share similar functions. They found that the activity of one group of genes involved in interferon signaling increased in infants who experienced a viral infection, including asymptomatic ones, before three months of life, compared with those who experienced a viral infection after month three. Interferons are a group of proteins produced in response to the presence of viruses.

Respiratory infections

The researchers found that stronger interferon activity was related to specific airway microbiota dynamics, including higher levels of Moraxella and Haemophilus bacteria early in life. These microbial profiles were linked to an increased number of respiratory tract infections during the infants’ first year of life.

Similarly, early abundance of Streptococcus was associated with a high number of respiratory tract infections, whereas early and prolonged abundance of Corynebacterium and Dolosigranulum was linked to a low number of respiratory infections, the team found.

More work is needed to confirm whether viral infections change immune and microbiota profiles in ways that increase the risk of respiratory infections, the researchers say. However, the findings suggest an intriguing link between viral encounters early in life and subsequent host–microbe cross-talk. “Since our data suggest that interactions between host and microbe already occur very early in life, future studies may want to focus in even more detail on this early window of life,” the authors say.