4. DISCUSSION
Ocular allergy represents one of the most common ocular surface
diseases. Despite an emerging picture of immunologic mechanisms
underlying AC, the etiology is not fully understood especially for
severe forms like VKC. In this study, we characterized the associations
of conjunctival microbiome dysbiosis with AC and identified the species
involved in the dysbiosis. Though it is unclear which aspects of the
microbial dysbiosis are causes or consequences of the onset of diseases,
these findings captured novel characteristics of AC. Future studies are
needed to clarify the roles of the discovered associated species in the
development and exacerbation of ocular allergy. Current treatment
regimens of AC mainly focus on suppressing inflammation, and combining
these first-line treatments with therapies targeting the ocular surface
microbiome may be beneficial.
The age distribution of the AC participants was older than
epidemiologically expected. This might be owing to temporal interval
between the first onset of AC and the time when they came to our
hospital. Although the age of healthy and AC participants were not
exactly matched, the age-associated species were absent from the species
identified in this study.10 This implies that age is
not the driver of microbiome differences between healthy and AC
participants in our study. In addition, it is unknown if the
colonization of these species predates the onset of AC (especially in
early life), highlighting the need for longitudinal studies to
investigate the transition to microbial dysbiosis in AC.
We did not find significant differences in species composition between
SAC and PAC, which is consistent with their similarity in signs and
symptoms. Most of the species with different abundance between SAC/PAC
and VKC were enriched in VKC. The involvement of type IV
hypersensitivity might be related to the overgrowth of these species. In
clinical practice, the allergens of SAC and PAC are often clear, whereas
the triggers of VKC are generally difficult to find. This highlights the
value of investigating the roles of microorganisms in VKC.
The incidence of allergic diseases is influenced by multiple factors.
For instance, personal life experiences lead to distinct allergen
profiles across individuals. Despite enrichment in AC, some species were
also present in healthy individuals, suggesting that other factors might
contribute to the pathogenicity of these species. Moreover, some
individuals with AC harbored one or a few prominent species unlike other
patients. For example, a sample from an eight-year-old boy with VKC
contained a non-negligible abundance (>10%) of human beta
herpesvirus 6A. This reflects the complexity and individuality of
microbial mechanisms in AC.
It is of particular interest that some species enriched in AC have been
previously shown to contribute to other allergic diseases like atopic
dermatitis and asthma. This suggests that various allergic disorders
might have some microbial mechanisms in common. Specifically, the ocular
surface is connected with the nasopharynx through the nasolacrimal
canal. This connection may facilitate the exchange of pathogenic
species. Further studies are required to provide evidence for the
similar roles of these species on conjunctiva as on other mucosal
surfaces. Apart from local airways microbiome, gut microbiome also plays
a part in asthma. Likewise, the association of gut microbiome and AC is
worth investigating.
Of note, many of the species involved in AC overlapped the most
niche-associated (showing great phylogenetic separation between body
sites) species identified by the Human Microbiome
Project,33 such as Haemophilus parainfluenzae ,Rothia dentocariosa , and Streptococcus sanguinis . It is
very likely that ocular surface harbors unique strains of these species
emphasizing the need for further efforts to characterize the genomes of
species living on the ocular surface. These efforts may include whole
genome sequencing on the isolates cultured from ocular surface samples,
as well as large-scaled metagenome assembly. Further investigation will
lead to a better understanding of how specific strains of these
microorganisms are associated with AC.
Besides small sample size, a limitation of this study is that AKC was
not included. AKC is least common and its pathologic mechanism is
considered similar with that of VKC. In addition, we only sampled from
inferior bulbar conjunctiva while other parts of the ocular surface
(lid, cornea, and other regions of conjunctiva) could also be affected
in AC.
In summary, our study characterizes and contextualizes the conjunctival
microbiome dysbiosis in AC. The microbiome signatures identified here
represent potential targets for follow-up studies on the microbial
mechanisms that underlie AC and other non-infectious ocular surface
inflammations.