Nasal Microbiome Study Redraws the Map of Staphylococcus aureus Carriage

A large population study of the human nasal microbiome is reshaping how clinicians think about Staphylococcus aureus carriage and the risk it poses for infection.

In a study published in Nature Communications, Dinesh Aggarwal, PhD, MA, MBBS, DTM&H, MRCP, FRCPath, Ewan Harrison, PhD, and colleagues analyzed nasal swabs from 1180 “generally healthy” adults across England who were enrolled in the CARRIAGE study. Participants sent in weekly swabs for 3 weeks so the team could classify them as persistent carriers, intermittent carriers, or non-carriers of S aureus using traditional culture methods. The same samples were also sequenced to map the wider bacterial community living in the nose.

Participants had an average age of 51.4 years (median: 53), with 52.8% being female. A total of 1756 samples, including initial swabs from 1180 participants, underwent 16S rRNA gene sequencing to analyze their microbiome composition.

The authors note that, unlike the gut, “the nasal microbiome has not been studied in large numbers of people.” This dataset, they write, provides “a comprehensive view of the nasal microbiome with respect to S aureus [colonization].”

One of the clearest signals was that people who are persistently colonized look very different from everyone else at the microbial level. Around 28% of participants were persistent carriers by culture. In roughly half of them, S. aureus accounted for more than 50% of all bacterial reads 136/275 (49.5%), and in about one-third, it accounted for more than 75% 96/275 (34.9%). The authors describe a “community state type” (CST) dominated by S aureus, in which the pathogen essentially shapes the rest of the nasal microbiome. These samples had lower diversity and were more stable over time than those from non-carriers.

By contrast, noncarriers showed a range of alternative CSTs in which S aureus was rare or absent. These communities were typically dominated by other residents, particularly several Corynebacterium species and Dolosigranulum pigrum. Using a differential abundance analysis, the team found persistent carriage was “positively associated with S aureus abundance, and negatively associated” with 3 Corynebacterium species, D pigrum, Staphylococcus epidermidis, and Moraxella catarrhalis. In other words, when these organisms flourished, S aureus tended not to.

The long-standing category of “intermittent carrier” did not hold up well under microbiome scrutiny. Ordination plots showed that intermittent carriers did not form a distinct cluster. Instead, their microbial communities overlapped with either persistent carriers or noncarriers. When the team looked more closely, people with only 1 culture-positive swab tended to have microbiomes similar to those of noncarriers, while those with 2 positive swabs looked more like persistent carriers. The authors conclude that intermittent carriage “is not a unique state” but reflects individuals who are either transiently exposed or misclassified persistent carriers.

To test whether the microbiome could be used to predict colonization status, the investigators built a random forest model based on species abundances. Overall accuracy on a test set was about 755, with particularly strong performance for identifying persistent carriers and true non-carriers. The most important features in the model were S aureus itself, Corynebacterium species, S epidermidis and D pigrum. The authors suggest that microbiome-informed models could eventually “improve the identification of true negatives in S aureus screening” and help target decolonization strategies to those at highest risk.

“We show that persistent S. aureus carriage is strongly associated with a distinct nasal microbiome CST dominated by S aureus, while non-carriers exhibit diverse CSTs with low S aureus abundance; intermittent carriers are not a unique state but have microbiomes that resemble non- or persistent carriers,” the authors wrote. “We show that machine learning models leveraging microbiome composition can accurately predict colonization persistence, and that certain S aureus lineages are more adept at establishing nasal colonization.”

The study, titled “Large-Scale Characterisation of the Nasal Microbiome Redefines Staphylococcus aureus Colonisation Status,” also linked colonization patterns to bacterial lineage. Using whole-genome sequencing of 172 S aureus isolates, the team found that certain sequence types, clustered in 1 major phylogenetic branch, reached higher nasal abundances and were more often associated with the S aureus-dominated CST. This implies that “certain S aureus lineages are better adapted to colonization than others,” with potential implications for transmission and infection risk.

Beyond redefining carriage categories, the findings strengthen the case for microbiome-based interventions. Several organisms negatively associated with S aureus have already been explored as potential live biotherapeutics. The authors point out that antagonistic nasal strains, such as Corynebacterium species or D pigrum, could help achieve colonization resistance without relying on antibiotics.

Taken together, the work suggests there are 2 biologically meaningful nasal states. In one, S aureus dominates and suppresses competing bacteria, creating a stable, low-diversity community that may increase infection risk. In the other, a consortium of commensal species occupies the niche and keeps S aureus at low levels or out of the nose altogether. Understanding how to shift people from the first state to the second could be key to future prevention strategies for S aureus disease.