Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate

Psoriatic skin has reduced GPR109A expression, topical sodium butyrate increases GPR109A expression in skin and is potentially useful in psoriasis therapy.

Overview

This 2018 study (PubMed 30209581) investigated GPR43 and GPR109A receptor expression in psoriatic skin compared to healthy skin. Key findings: psoriatic plaques show significantly reduced GPR109A (and GPR43) expression, and topical application of sodium butyrate can restore GPR109A expression in psoriatic skin. This adds molecular detail to the connection between the niacin receptor, gut metabolites, and inflammatory skin disease.

GPR109A in the Skin

GPR109A is a G-protein-coupled receptor expressed in fat cells (where niacin activates it to cause the characteristic flush), immune cells, colonic epithelium, and skin cells including keratinocytes. When activated, GPR109A generally produces anti-inflammatory effects: reduced cytokine production, promotion of regulatory immune responses, and reduced oxidative stress. In skin cells, GPR109A activation may help regulate the immune hyperactivation that characterizes psoriasis.

What the Study Found

Psoriatic skin has lower GPR109A expression. Skin biopsies from psoriasis patients showed significantly reduced expression of both GPR109A and GPR43 compared to healthy skin. The molecular brake on inflammation — the receptor that niacin or butyrate would normally activate — is less available in psoriatic tissue.

Topical sodium butyrate restores GPR109A. When sodium butyrate was applied topically to psoriatic skin, GPR109A expression increased. This suggests the reduced receptor expression is not permanent and can be upregulated by its natural ligand.

Why Butyrate?

Butyrate is a short-chain fatty acid produced by gut bacteria fermenting dietary fiber. It activates both GPR43 and GPR109A — the same receptor that niacin activates, though through different binding kinetics.

Connection to Niacin

This paper is part of a growing literature suggesting that reduced GPR109A activity in skin may be a feature — not just a consequence — of psoriasis, and that restoring GPR109A function through its known agonists (niacin, butyrate) could be therapeutically relevant.

Nicotinic acid activates GPR109A in keratinocytes and skin-resident immune cells. A related keratinocyte study also showed that nicotinic acid (not niacinamide) preferentially raises NAD+ in skin cells. Together, these findings suggest a mechanistic basis for investigating nicotinic acid specifically — not the niacinamide used in skincare — for psoriasis research.

Implications

• Psoriatic skin has a deficit in the anti-inflammatory receptor that niacin and butyrate activate
• This deficit may contribute to the inability of psoriatic tissue to resolve inflammation normally
• Restoring GPR109A expression via topical or systemic agonists is a potential therapeutic avenue
• The interplay between gut microbiome health, dietary fiber, and skin inflammation has a plausible molecular mechanism through GPR109A