Gut bacteria producing phenols disturb keratinocyte differentiation in human skin

Abstract

Objective: Our previous study suggested that phenols (phenol and p-cresol ) produced by gut bacteria affect the skin in hairless mice. In the present study we aimed to determine if the same phenomenon is applicable to humans. Methods : First, we analyzed the correlation between serum phenol levels and corneocyte size in 50 healthy female volunteers. Second, we administered a prebiotic beverage (containing galacto-oligosaccharides and polydextrose) to 19 healthy female volunteers and examined the correlations among fluctuation of phenol levels, corneocyte size, and cathepsin L-like activity. Finally, we performed an in vitro experiment using monolayer-cultured human keratinocytes to determine whether phenols physiologically affected keratinocyte differentiation. Results : In 50 healthy female volunteers, serum phenol levels showed a significant inverse correlation with skin corneocyte size. When a prebiotic beverage was administered for 3 weeks to 19 healthy female volunteers, p-cresol levels decreased significantly, and significant increases in corneocyte size and cathepsin L-like protease activity were seen. On in vitro examination, monolayer-cultured human keratinocytes subjected to 20 nmol/ml phenol or p-cresol failed to express K10 protein (a molecular marker for normal keratinocyte differentiation) under physiological conditions. Conclusions : These results suggest that phenols produced by gut bacteria adversely affect keratinocyte differentiation in female human skin. Furthermore, these results indicate that serum phenol levels are appropriate biomarkers of keratinocyte differentiation disturbances caused by an undesirable intestinal environment in humans. Key words: Phenol, p-cresol, biomarker, gut bacterial metabolites, intestinal environment, keratinocyte differentiation, galacto-oligosaccharides