The Montash University team devised an experimental model to trigger skin barrier dysfunction and allergen sensitization in weanling mice through repeated exposure to house dust mites (HDM) allergens.
Reductions in skin barrier transgressions, allergen ingress and sensitization, as well as decreased AD-like skin inflammations (ADLSI) were observed in mice administered a high-fibre diet (HFD) or orally administered with butyrate-rich short-chain fatty acids (SCFA).
Butyrate was detected in the skin just 45 minutes after ingestion and mitigated systemic allergen sensitization.
The authors maintain their findings offer useful insight for potential treatments to prevent or treat allergies.
Barrier integrity
The outer skin epidermis is “the cornerstone of skin barrier function”, the researchers explain. It is composed of keratinocytes that produce structural proteins and lipids to prevent genetic mutations, impaired immunity, and the ingress of environmental factors like pollutants, allergens, and microbes.
Sensitivity to allergies is dependent on skin barrier integrity and when compromised allergens are more likely to infiltrate and provoke AD - a chronic and recurrent inflammatory disease, they say.
The condition emerges in early childhood and facilitates the onset of food allergies, allergic rhinitis, and asthma in later life – a phenomenon dubbed the ‘atopic march’.
Lifestyle allergies
Evidence indicates that childhood allergies are driven by low levels of dietary fibre derived SCFA’s, and especially butyrate that strengthens the skin barrier. They affect approximately 20% of children globally.
Recent allergic epidemics are also linked to environmental and behavioural changes, known collectively as ‘Westernised lifestyles’, the authors write.
“Such a lifestyle could cause epithelial barrier dysfunction, an event leading to enhanced ingress of allergens at mucosal surfaces, systemic allergen sensitization, and ultimately the development of allergic diseases.”
Dietary fibre and SCFA are known to modulate immune responses to inflammatory episodes and promote metabolism of keratinocytes, although knowledge about their impact on non-immune responses is limited.
In the current study, the authors hypothesized that low fibre intake supports skin barrier dysfunction and a propensity for early allergen sensitization.
Mechanistic process
Supplementation with either formula (HFD or LFD with added butyrate) accelerated epidermal keratinocyte differentiation and enhanced production of key structural proteins and lipids, leading to strengthening of the stratum corneum, the authors said.
Mice on HFD displayed decreased epidermal thickening and immune cell infiltration, demonstrated through analysis of hematoxylin and eosin (H&E)-stained lesional skin sections. Compared to mice on the control diet with poorly fermented cellulose, they exhibited lower disease severity and improved barrier integrity, as determined by measurement of trans-epidermal water loss (TEWL).
Likewise, mice administered a low fibre diet, supplemented with SCFA, exhibited similar improvements to those incurred by HFD and were mainly attributed to the presence of butyrate.
Further analysis
Gene ontology (GO) confirmed the mechanistic role of butyrate in immune support and skin barrier protection in treated mice. Skin analysis from butyrate-treated mice revealed an abundance of differentiated gene and terminal cornified keratinocytes that promote epidermal protection.
Further tests demonstrated the capacity of butyrate to alter lipid metabolism in epidermal keratinocytes and especially following allergen-mediated skin injury.
The authors conclude: “Our work highlights the gut-skin axis as a central mechanism underpinning protection against allergies and atopic dermatitis.
“Results demonstrate that dietary fibre consumption and SCFA are pivotal factors that can help maintain skin barrier integrity and limit allergen sensitization, a finding of significant importance in the context of the atopic march.”
Source: Mucosal Immunology
Published online: doi.org/10.1038/s41385-022-00524-9
‘Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation’
Aurélien Trompette et al.