Abstract
Influenza is a major cause of morbidity and mortality worldwide. However, vaccine effectiveness has been low to moderate in recent years and vaccine coverage remains low, especially in low- and middle-income countries. Supplementary methods of prevention should be explored to reduce the high burden of influenza. A potential target is the respiratory tract microbiome, complex microbial communities which envelop the respiratory epithelium and play an important role in shaping host immunity. Using a household transmission study, we examined whether the nose/throat microbiota was associated with influenza susceptibility among participants exposed to influenza virus in the household. Further, we characterized changes in the nose/throat microbiota to explore whether community stability was influenced by influenza virus infection. Using a generalized linear mixed effects model, we found a nasal/oropharyngeal community state type (CST) associated with decreased susceptibility to influenza. The CST was rare and transitory among young children but a prevalent and stable CST among adults. Using boosting and linear mixed effects models, we found associations between the nose/throat microbiota and influenza also existed at the taxa level, specifically with the relative abundance of Alloprevotella, Prevotella, and Bacteroides oligotypes. We found high rates of change between bacterial community states among both secondary cases and household contacts who were not infected during follow up. Further work is needed to separate the effect of influenza virus infection from the considerable short-term changes that occur even in the absence of virus. Lastly, age was strongly associated with susceptibility to influenza and the nose/throat bacterial community structure. Although additional studies are needed to determine causality, our results suggest the nose/throat microbiome may be a potential target for reducing the burden of influenza.
Highlights
Influenza is a major contributor of human illness and death worldwide, estimated to cause 3–5 million cases of severe illness [1] and 400,000 deaths during interpandemic years [2]
Analysis was restricted to 537 household contacts who were negative for influenza virus by real-time reverse transcription polymerase chain reaction (RT-PCR) at time of enrollment
We found household contacts with NOP community state type (CST) 4 had a lower odds of influenza virus infection (odds ratio (OR): 0.26; 95% CI: 0.07, 0.99) (Fig 4), Further, young children were most likely to acquire influenza virus (OR: 4.66; 95% CI: 1.62, 13.37), followed by older children (OR: 2.91; 95% CI: 1.47, 5.80)
Summary
Influenza is a major contributor of human illness and death worldwide, estimated to cause 3–5 million cases of severe illness [1] and 400,000 deaths during interpandemic years [2]. With increasing support for a role of the microbiome in shaping host immunity [6,7,8], exploring whether these effects extend to influenza risk could contribute to supplementary methods of prevention. Mice treated with oral antibiotics exhibited enhanced degeneration of the bronchiole epithelial layer and increased risk of death following intranasal infection with influenza virus [7]. In two separate randomized controlled trials, newborns fed prebiotics and probiotics had significantly lower incidence of respiratory tract infections compared to placebo [9,10]. These studies suggest the manipulation of the microbiome, either through disruption or supplementation, can alter risk of respiratory tract infections
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