Middle ear infections are one of the most common ailments of childhood. But not everyone is equally susceptible – why? A research group at the University of Colorado’s Anschutz Medical Campus has discovered a way to identify those who may be more at risk. Describing for the first time the expression of the FUT2 gene in the middle ear (1), the researchers found that levels spike within 24 hours of bacterial infection, and also that certain variants of the gene alter the overall microbiome of the middle ear.
“FUT2 was identified as a protective locus against otitis media susceptibility in a genome-wide association study (2),” says first author Regie Santos-Cortez. “However, when we looked at the sequence data from our multi-ethnic families, we saw that the FUT2 variants conferred risk for otitis media.”
How does the gene interact with the microbiome to elevate the risk of disease? “Middle ear swabs in FUT2 variant carriers had greater bacterial diversity, meaning that the types of bacterial groups in variant carriers are different – and relatively higher in number – than in non-carriers,” Santos-Cortez explains. “This suggests that the bacterial load in the middle ear, including potential pathogens, is increased in those with genetic susceptibility to disease.” By decreasing the presentation of the A antigen bacteria use to enter the middle ear lining, the variants cause a shift in the microbiome, decreasing some bacterial populations and increasing others – including some known to promote chronic or recurrent infections.
What’s next? Santos-Cortez suggests that microbiota transplants might help restore the normal middle ear microbiome in variant carriers. “What we need to know at this point are the good commensal bacteria that we would want to restore to healthy levels to outcompete the pathogenic bacteria,” she says. “We would also want to have more directed therapies, such as antibiotic treatments, that target specific pathogenic bacteria without affecting the healthy commensals.” Meanwhile, she and her colleagues intend to continue finding genetic variants in relation to the middle ear microbiome to improve otitis media management in every population.
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References
- RLP Santos-Cortez et al., “FUT2 variants confer susceptibility to familial otitis media”, Am J Hum Genet, 103, 679–690 (2018). PMID: 30401457. JK Pickrell et al., “Detection and interpretation of shared genetic influences on 42 human traits”, Nat Genet, 48, 709–717 (2016). PMID: 27182965.
