Distinct skin microbiome community structures in congenital ichthyosis

Abstract

Background The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored. Objectives To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes. Methods Body site‐matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis. Results Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and Corynebacterium genera, as well as shifts in fungal species, including Malassezia. Malassezia globosa was reduced at all body sites, whereas M. sympodialis was reduced in the ichthyotic upper arm and upper buttocks. Malassezia slooffiae, by contrast, was strikingly increased at all body sites in participants with congenital ichthyosiform erythroderma (CIE) and lamellar ichthyosis (LI). A previously undescribed Trichophyton species was also detected as sporadically colonizing the skin of patients with CIE, LI and epidermolytic ichthyosis subtypes. Conclusions The ichthyosis skin microbiome is significantly altered from healthy skin with specific changes predominating among ichthyosis subtypes. Skewing towards the Th17 pathway may represent a response to the altered microbial colonization in ichthyosis. What is already known about this topic? The skin microbiome of congenital ichthyoses is largely unexplored. Microbes play an important role in pathogenesis, as infections are common. The relative abundances of staphylococci and corynebacteria is increased in the cutaneous microbiome of patients with Netherton syndrome, but extension of these abundances to all congenital ichthyoses is unexplored. What does this study add? A common skin microbiome signature was observed across congenital ichthyoses. Distinct microbiome features were associated with ichthyosis subtypes. Changes in microbiome may contribute to T helper 17 cell immune polarization. What is the translational message? These data provide the basis for comparison of the microbiome with lipidomic and transcriptomic alterations in these forms of ichthyosis and consideration of correcting the dysbiosis as a therapeutic intervention.

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients

“…Prior to this study, there was limited data to understand the microbiome and immunological signatures accompanying the various ichthyoses, and even less data across races or ethnicities. We note after preparation of this report a microbiome study on 22 CI patients from 4 types (Congenital ichthyosiform erythroderma (CIE), LI, EI, Netherton’s Syndrome (NS)) was published [26]. Using WES we fully characterized the mutations underlying disease in 36 CI patients belonging to 7 CI types with Southeast Asian ethnicity, identifying 20 novel variants.…”

Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases

“…Epidermolytic Ichtyosis (EI), Netherton syndrome (NS) lamellar ichtyosis and congenital ichtyosiform erythroderma (CIE) are known to show the highest prevalence. Lipidomics analysis of skin surface samples from ichtyosis patients and controls showed that the skin microbiome is markedly altered from healthy skin, and specific alterations predominate in various ichtyosis subtypes [ 130 ].…”

Impaired epidermal barriers in congenital ichthyoses house a changing microbial landscape

“…In this issue of the BJD, Tham and colleagues profiled the skin microbiome of 22 subjects with congenital ichthyoses compared with healthy controls. 3 This study investigated the skin microbiome of four types of congenital ichthyosis [autosomal recessive congenital ichthyosis (ARCI): congenital ichthyosiform erythroderma (CIE), lamellar ichthyosis (LI), epidermolytic ichthyosis (EI) and Netherton syndrome (NS)] in order to investigate potential differences in microbiome composition between subtypes. Subjects with and without ichthyosis were sampled by skin swab at body site-matched locations (scalp, upper arm, upper buttock) and wholemetagenomics sequencing analysis was performed to profile the bacteria, fungi and viruses.…”

“…Based on their findings and prior studies, 6,7 Tham and colleagues propose an interesting hypothesis, namely, that increased relative abundance of Staphylococcus, Corynebacterium, Malassezia and Trichophyton species contribute to the known Thelper (Th)17 immune polarization in disorders of cornification. 3 All these organisms are known to activate the Th17 pathway and contribute to skin inflammation in other contexts, but have not been previously described in ichthyosis. It is also possible that increased skin inflammation and barrier disruption further contribute to microbial dysbiosis in these patients, creating a chronic inflammatory cycle.…”

“…Prescribed and recreational drug use enquiry is crucial, with anti-Parkinsonian medication, gabapentin, ciprofloxacin, antimalarials, cocaine, cannabis and amphetamines possible culprits. 2,3 Urine toxicology screening is mandatory and may need repeating. Coexisting psychiatric symptoms of anxiety and depression should be sought, ideally using validated assessment tools, and treated.…”