Maurice Adrianus Monique van Steensel

Background: Axillary malodor is primarily caused by bacteria, particularly Staphylococcus hominis , which metabolize apocrine secretions into volatile compounds. Traditional deodorants contain antiseptics that can disrupt the skin microbiome and cause irritation. Alternative methods of odor control are being sought but so far without success. We considered bacteriophage lysins, as these can target specific bacteria and thus offer a more microbiome‐friendly alternative. Objectives: Thus, we sought to determine efficacy and safety of a recombinant lysin in reducing axillary malodor, and to assess the lysin's effect on the skin microbiome. Methods: We conducted a consumer trial to evaluate the efficacy of a proprietary lysin, supported by in vitro and in vivo safety testing as well as microbiome analysis. Results: We demonstrated rapid, sustained odor reduction upon application of a lysin, without skin irritancy and preserving the skin microbiome's diversity. With these outcomes, we address a significant consumer concern. Conclusions: We present the first clinically effective use of bacteriophage lysins to control axillary malodor in humans. Our study outcomes favor the use of lysins for microbial control in personal care and other applications.

In this study, we demonstrate that Benzo[a]pyrene (B[a]P) induces keratinocyte senescence and p21 ^Cip1 -dependent keratinocyte differentiation. Atmospheric and environmental pollution are known to induce senescence and promote terminal differentiation in human primary keratinocytes, thus driving skin aging. However, much is still unknown about the underlying molecular mechanisms. We observed that B[a]P, a common atmospheric pollutant, induced senescence in primary keratinocytes in both two-dimensional and three-dimensional (reconstructed human epidermis) culture. This was accompanied by signs of DNA damage in B[a]P-treated cells. B[a]P-treated cells also underwent accelerated late-stage terminal differentiation, indicated by increased IVL and FLG expression from 48 to 96 hours post-exposure. While pharmacological and genetic attenuation of p21 ^Cip1 did not rescue cellular senescence, it prevented the expression of IVL and FLG , suggesting that the late-stage terminal differentiation induced by B[a]P exposure was p21-dependent. Our data thus suggest a key role for the p21 ^Cip1 in the keratinocyte response to pollution-induced damage, where p21 ^Cip1 induces terminal differentiation to maintain skin barrier homeostasis.

This review discusses the microbiology of acne vulgaris, a chronic inflammatory condition of the pilosebaceous unit that affects most adolescents and can persist into adulthood. The current standard of care consists largely of antibacterial interventions, based on the traditional view of Cutibacterium acnes as a pathogen. Alternative treatments are suggested by the “comedo switch” hypothesis, which attributes acne to aberrant differentiation of LRIG1+ sebaceous progenitor cells. While there is strong evidence to support this idea, it does not explain the efficacy of antibacterial interventions. We propose a unified mechanism wherein C. acnes phylotype IA1 can act as a trigger for the comedo switch. Unlike commensal strains, phylotype IA1 has high lipase activity, hydrolyzing sebum triglycerides into free fatty acids, specifically palmitic acid. This metabolite stimulates LRIG1+ progenitors, inducing inflammation and initial comedo formation. The review discusses C. acnes phylotypes, emphasizing known virulence factors of IA1, such as enhanced biofilm formation. We evaluate the efficacy and limitations of both old and new antibacterials, noting how newer materials that selectively remove C. acnes IA1 can reduce non-inflammatory acne lesions, supporting a key role for this phylotype in the pathogenesis of acne.

This review discusses the microbiology of acne vulgaris, a chronic inflammatory condition of the pilosebaceous unit that affects most adolescents and can persist into adulthood. The current standard of care consists largely of antibacterial interventions, based on the traditional view of Cutibacterium acnes as a pathogen. Alternative treatments are suggested by the "comedo switch" hypothesis, which attributes acne to aberrant differentiation of Lrig1+ sebaceous progenitor cells. While there is strong evidence to support this idea, it does not explain the efficacy of antibacterial interventions. We propose a unified mechanism wherein C. acnes phylotype IA1 can act as a trigger for the comedo switch. Unlike commensal strains, phylotype IA1 has high lipase activity, hydrolyzing sebum triglycerides into free fatty acids, specifically palmitic acid. This metabolite stimulates Lrig1+ progenitors, inducing inflammation and initial comedo formation. The review discusses C. acnes phylotypes, emphasizing known virulence factors of IA1, such as enhanced biofilm formation. We evaluate the efficacy and limitations of both old and new antibacterials and in this context present a novel material that disrupts C. acnes biofilms (SmartArrow™). In a trial of 34 subjects with mild-to-moderate acne, this non-antibiotic agent demonstrated a statistically significant reduction in inflammatory lesions and selectively depleted phylotype IA1 by 37%, without compromising microbiome diversity. Our findings support the causal role of C. acnes IA1 in acne inflammation as well as in the comedo switch, and suggest that biofilm disruption represents a promising therapeutic avenue.

This review addresses the genetics of acne vulgaris, the most common skin disease. It is characterized by the presence of comedones (blackheads), papules, and pustules. The condition is associated with sebaceous glands in the face and chest, which produce an oily substance called sebum. In developed nations, acne affects over 80% of adolescents. Mild disease usually resolves spontaneously. More severe acne can leave permanent, disfiguring scarring and strongly affects quality of life. In those cases, medical intervention is warranted. To date, antibiotics and retinoids (synthetic vitamin A derivatives) are the mainstays of treatment. Depending on the severity of the condition, these drugs may be administered either topically or systemically. Whilst generally effective, they do come with significant drawbacks. Antibiotic use for treating acne is contributing to antimicrobial resistance. In addition, indiscriminate eradication of the skin microbiome negatively impacts skin health. Retinoids are teratogenic and have other undesirable side effects, such as skin irritation and increased UV sensitivity. Thus, there is a clear need for effective interventions that target the underlying disease mechanism, minimizing side effects. Rapid progress has recently been made in understanding the mechanisms underlying acne. For decades, it was assumed that blackhead formation results from the accumulation of sebum in the hair follicle opening, due to increased sebum production at the onset of puberty. Subsequent colonization by the commensal bacterium Cutibacterium acnes then was thought to cause inflammation. It was also postulated that this micro‐organism could induce blackheads. There are, however, several problems with this supposed sequence of events, not the least of which is that it doesn't explain how retinoids work, or why sebaceous glands associated with blackheads are atrophic and hence produce less sebum, not more. Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne. Together with insights from mouse models, this new perspective is transforming the way we think about acne and its treatment.

Skin ageing is a complex process. Both intrinsic and extrinsic factors have a role in determining the speed, progression and phenotypic outcomes of the process. Typical clinical signs of ageing, such as wrinkles, thinning and sagging of the skin, are usually first noticed in the mid‐20s to early 30s. However, real‐world studies report that younger Asian women between the ages of 18 and 24 years are perceiving emerging signs of ageing, including dull skin, uneven skin tone, dryness, transient wrinkles, and a lack of skin firmness. These observations have led to a hypothesis that a phase of preageing may exist, where clinical signs of ageing are not yet present, but an individual starts to notice subtle changes in their skin's appearance. This paper discusses the concept of preageing in Asian populations and provides recommendations for recognising and managing the preageing process in clinical practice.