Overview
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease characterized by painful nodules, abscesses, and sinus tracts in apocrine gland-bearing skin (axillae, groin, inframammary folds). Long classified as a purely dermatological condition, emerging evidence reveals HS as a systemic inflammatory disorder with a significant gut microbiome component — connecting it to the broader gut-skin axis framework.
Microbiome Associations
Gut Microbiome
Mendelian randomization analysis has identified two gut taxa with causal risk effects on HS:
- Clostridium innocuum group — OR 2.17 (P = 0.00038); the strongest causal signal [1]
- lachnospira — OR 2.45 (P = 0.017); a paradoxical risk association for an SCFA-producing genus, suggesting that the mechanism may involve SCFA-mediated alteration of cutaneous immune responses rather than simple inflammation [1]
Remarkably, 40% of HS patients harbor a gut microbiota configuration similar to Crohn's disease, characterized by enrichment of pathogenic genera and depletion of beneficial genera including faecalibacterium prausnitzii [2]. This overlap is consistent with clinical observations that HS and CD frequently co-occur and share TNF-alpha-driven pathology.
Skin Microbiome
The HS lesional skin microbiome shows enrichment of anaerobic and biofilm-forming organisms in sinus tracts, including Prevotella, Porphyromonas, and coagulase-negative staphylococci. The tunneling nature of HS sinus tracts creates anaerobic microenvironments that may select for specific pathobiont communities — paralleling the oxygen-dependent ecological dynamics seen in gut dysbiosis.
Metal Associations
Direct metal studies in HS are limited. However, the strong overlap with Crohn's disease microbiome patterns and shared TNF-alpha-driven inflammation suggest that metal-microbiome dynamics relevant to CD — including iron-siderophore competition and zinc-dependent metalloprotease activity — may operate in HS as well. Nickel allergy, which is highly prevalent in inflammatory skin conditions, has not been systematically studied in HS but represents a plausible connection given nickel's role in immune sensitization.
Associated Conditions
- crohns disease — 40% gut microbiota overlap; shared TNF-alpha pathology; clinical co-occurrence well-documented. Both conditions respond to anti-TNF therapy (adalimumab is approved for both).
Environmental Factors
- Diet — Western diet patterns (high-fat, low-fiber) are associated with HS severity, consistent with the gut-microbiome-mediated mechanism
- Smoking — Strong independent risk factor; may influence both skin and gut microbiome composition
- Obesity — Mechanical and inflammatory contributor; shared metabolic endotoxemia pathway
Key Studies
- [1] — Two-sample MR identifying causal gut taxa (cross-sectional/MR design)
- [2] — 40% HS-CD gut microbiome overlap
Open Questions
- Does the Lachnospira risk association operate through SCFA-mediated cutaneous immune modulation, or through a different mechanism?
- Would dietary interventions targeting the gut microbiome (fiber supplementation, Mediterranean diet) improve HS outcomes?
- Are the shared CD-HS microbiome features a cause or consequence of shared genetic susceptibility at TNF pathway loci?
Cross-References
- crohns disease — shared gut microbiome configuration and TNF-alpha pathology
- lachnospira — causal risk factor via MR analysis
- faecalibacterium prausnitzii — depleted in HS gut microbiome (CD-like pattern)
- barrier-dysfunction — gut permeability as route for systemic inflammation affecting skin