This randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the safety and efficacy of topical palmitoleic acid glyceride supplementation in improving skin barrier impairment associated with chronic dermatitis, with a particular focus on the interaction between physical activity, skin microbiota, and lipid metabolism.

Emerging evidence suggests that regular physical activity reshapes the skin microenvironment, including alterations in sebaceous lipid composition and enrichment of Staphylococcus epidermidis, which possesses lipase activity capable of metabolizing glycerides into bioactive fatty acids. Palmitoleic acid, a key lipid metabolite derived from palmitoleic acid glycerides, has demonstrated anti-inflammatory and barrier-protective properties in preclinical and clinical settings. However, it remains unclear whether restoring exercise-associated lipid metabolites through topical application can improve skin barrier dysfunction in individuals with chronic dermatitis, and whether physical activity status modifies therapeutic efficacy.

Research Objectives：

1. Does topical application of low-concentration palmitoleic acid glyceride improve skin barrier function, as measured by transepidermal water loss (TEWL), in individuals with chronic dermatitis?
2. Does physical activity status influence the therapeutic response to palmitoleic acid glyceride treatment?
3. Are improvements in skin barrier function associated with changes in skin microbiota composition, microbial lipase activity, and lipid metabolism at the skin surface?

Study Design and Group Allocation：

Eligible male/female participants aged 18-59 years with clinical manifestations of chronic dermatitis and evidence of skin barrier impairment will be enrolled. Based on metabolic equivalents (MET) levels outside of daily living activities, participants will be divided into sedentary group and exercise group. Within each stratum, participants will be randomly assigned in a 1:1 ratio to receive either topical palmitoleic acid glyceride or placebo, resulting in four study groups:

1. Inactive Placebo Group: No regular physical activity; topical placebo.
2. Inactive Intervention Group: No regular physical activity; topical tripalmitoleoylglycerol.
3. Active Placebo Group: Regular physical activity; topical placebo.
4. Active Intervention Group: Regular physical activity; topical tripalmitoleoylglycerol.

Participant Procedures：

1. Daily topical application of either 0.5% tripalmitoleoylglycerol or placebo to a predefined skin lesion area for 30 consecutive days.
2. Non-invasive assessment of skin barrier function, including TEWL measurements, at baseline and after completion of the intervention.
3. Clinical evaluation of skin symptoms, including erythema, scaling, and pruritus, using standardized scoring systems (PASI or SCORAD, as appropriate).
4. Collection of skin swab samples for microbiome and metabolomic analyses to assess microbial lipase activity and palmitoleic acid production.
5. Weekly follow-up assessments to monitor treatment adherence and record any adverse events, particularly local skin reactions.

This study seeks to elucidate a novel exercise-microbiota-lipid axis in skin barrier regulation and to provide translational evidence for metabolite-based therapeutic strategies in chronic inflammatory skin diseases.

Inclusion Criteria：

1. Participants were classified into two groups based on their self-reported levels of physical activity (quantified in metabolic equivalent minutes per week [MET-min/week]): the non-exercising group (MET = 0): individuals who reported no moderate- or vigorous-intensity physical activity beyond activities of daily living. In this context, a value of 0 MET-min/week indicates that no structured or intentional exercise exceeding the threshold of basal metabolic rate was performed. Exercise group (MET > 0): This group includes any individual who engages in at least some level of physical activity, with a calculated MET-min/week value greater than 0.
2. Presence of clinical manifestations of skin barrier impairment, such as skin dryness, erythema, scaling, or pruritus;
3. Voluntary participation with full understanding of the study and provision of written informed consent;
4. Age between 18 and 59 years, with generally good health status;
5. No use of any medications or probiotic treatments within the past 6 months;

Exclusion Criteria：

1. History of allergy or known hypersensitivity to probiotics, placebo, or investigational products;
2. Presence severe systemic diseases;
3. Pregnant or breastfeeding women;
4. Use of medications that may affect skin barrier function, such as corticosteroids or immunosuppressive agents;
5. Any other condition deemed inappropriate for study participation by the investigators, including but not limited to participants considered unreliable or unable to understand or comply with study assessments