Abstract

Background: Atopic Dermatitis (AD) in adults is a troublesome condition to treat because of its chronic condition and side effects of prolonged traditional treatments. Probiotics, with their use of the gut-skin axis, are an emerging adjunct treatment by controlling immune effects and facilitating dermal health. This systematic review discusses the efficacy, safety and mechanism of action of probiotic supplementation for adult AD.

Methods: We had 13 studies, 7 on Lactobacillus spp. (224 patients) and 6 on mixtures of probiotics (878 patients), in total 1,102 patients, with follow-up between 8 weeks and 12 months. Outcomes were AD severity (SCORAD/EASI), immunological and microbiome alterations, Quality of Life (QoL) and safety. Random-effects meta-analysis was performed where data allowed and qualitative themes were coded to elucidate mechanisms and implications.

Results: Probiotics, compared to placebo, significantly lowered AD severity (pooled Mean Difference [MD] = -12.3, 95% CI: -15.6 to -9.0, P<0.001), more in mild AD (MD = – 14.2) than in moderate-to-severe AD (MD = -10.8). Lactobacillus strains (e.g., L. salivarius LS01; 52.3% decrease) and multi-strain combinations (e.g., L. rhamnosus GG, L. casei, B. longum; 39.5% decrease) were equally effective, an effect borne out by recent meta-analyses (SMD: -4.0, 95% CI: -7.3 to -0.7). Immunologically, probiotics enhanced Th1/Th2 equilibrium (↓IL-4, ↑IFN-γ), suppressed IgE and elevated regulatory T-cells. Microbiome modulation entailed enhanced gut species richness and attenuated S. aureus colonization, strengthening the gut-skin axis. QoL was enhanced (e.g., DLQI change) and corticosteroid requirements declined. Safety was optimal, with few side effects (e.g., occasional gastrointestinal upset).

Conclusion: Probiotic supplementation is a safe, efficacious adjunctive treatment for adult AD, but mild-to-moderate AD only, with decreased severity, immune modulation, quality of life improvement and decreased reliance on traditional treatments. While there are consistent findings, heterogeneity (I²=65%, P<0.01) and short follow-ups call for large, standardized RCTs to establish long-term efficacy and streamline strain-specific protocols. Through June 05, 2025, probiotics hold strong potential to fill gaps in AD treatment, with potential implications for personalized therapeutic approaches.

Keywords: Probiotics; Atopic Dermatitis; Adult Ad; Gut-Skin Axis; Immunomodulation; Microbiome; SCORAD; Quality of Life; Meta-Analysis; Corticosteroid Reduction

Introduction

Atopic Dermatitis (AD) is an eczematous, relapsing pruritic chronic skin condition with eczematous lesions, xerosis and background of inflammation, with remitting and exacerbating course, frequently continuing from infancy into adulthood [1]. AD involves 10- 20% of children globally and continues in 10-15% into adulthood, becoming a major public health problem [1,2]. Its multifactorial etiology reflects complex interactions among genetic predispositions, immune dysregulation and environmental stimuli [3,4]. Mutations in the FLG gene, coding for filaggrin, a structural protein essential for epidermal barrier function, are the primary genetic determinants. Loss-of-function mutations weaken the stratum corneum, enhancing permeability to allergens (e.g., dust mites, pollen), irritants (e.g., soaps, detergents) and pathogens, triggering inflammatory cascades that underlie AD’s chronicity [4]. Immune dysregulation, which is mainly Th2 cell-mediated, worsens the condition by the production of cytokines such as Interleukin-4 (IL-4), IL-5 and IL-13, causing eosinophil recruitment and an increase in serum Immunoglobulin E (IgE) levels-features of allergic inflammation proportional to AD severity [3,5]. The environment, through exposure to aeroallergens, air pollution (such as particulate matter, cigarette smoke) and psychosocial stressors (such as anxiety, chronic stress), further deranges cutaneous homeostasis, perpetuating the relapsing nature of the disease [3].

Clinically, AD presents with symmetrically placed lesions on the face, neck and extensor surfaces of the skin in children and flexural surfaces (such as antecubital and popliteal fossae) in adults [3,6]. The quality of life is severely impaired by the condition, with pruritus interfering with sleep, causing fatigue, irritability and increased risks of depression and anxiety [7]. Severe cases can result in visible lesions and chronic pain, leading to social withdrawal and heightened psychological burden [7]. Diagnosis is based on clinical evaluation, such as distribution of the lesions, personal and family history of atopic diseases (i.e., asthma, allergic rhinitis) and pruritus as a cardinal symptom, with Hanifin and Rajka criteria offering an official model of evaluation with major (i.e., pruritus, characteristic morphology) and minor (i.e., xerosis, infantile onset) criteria to permit uniform rating in various settings [6]. Contemporary treatment includes skin rehydration, reduction of inflammation and prevention of flare-ups [3,7]. Emollients reinforce the epidermal barrier and topical corticosteroids have an anti-inflammatory effect, but long-term use leads to side effects like skin atrophy, telangiectasia and systemic absorption [4]. Non-steroid options like topical calcineurin inhibitors (tacrolimus, pimecrolimus) cause local immunosuppression with lesser danger for long-term application, especially in sensitive zones like the face [3,8]. Despite such interventions, therapeutic limitations have driven interest in more recent approaches targeting the skin microbiome, which is increasingly recognized as key to AD pathogenesis [9].

Cutaneous microbiota of heterogeneous mites, viruses, fungi and bacteria maintain cutaneous health, barrier function and modulation of immunity [10,11]. Commensals such as Cutibacterium acnes and Staphylococcus epidermidis synthesize antimicrobial peptides (e.g., bacteriocins) and compete with ecological niches for pathogens, increasing immunity and tolerance in the skin [10,11]. In AD, microbial dysbiosis-i.e., lowered diversity and overgrowth of Staphylococcus aureus (in >90% patients vs. <10% controls)-halts ongoing disease progression [12]. S. aureus aggravates inflammation through virulence factors (e.g., α-toxin, superantigens such as staphylococcal enterotoxins), inducing keratinocyte apoptosis, activating pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and enhancing Th2- induced responses by circumventing conventional antigen presentation [11,12]. Decreased microbial diversity also compromises barrier mechanisms, having a tendency to increase a pro-inflammatory state [12]. The gut-skin axis also accentuates systemic interactions, with gut dysbiosis increasing AD severity through bidirectional inflammatory and immune cascades [13,14].

These observations concerning the role of the microbiome have given a push for researching therapies to re-establish microbial homeostasis and probiotics represent a novel promising area [15]. Living bacteria or yeast that, in appropriate quantities ingested, convey health advantages probiotics (Lactobacillus, Bifidobacterium, Saccharomyces) control gut and dermal microbiota and modulate immunity [13,16,17]. They restore Th1/Th2 homeostasis by enhancing anti-inflammatory cytokines (e.g., IL-10, TGF-β) and suppressing overexpressed pro-inflammatory cytokines (e.g., IL-4, IL-5, IL-13) in AD [17]. Probiotics also suppress pathogens such as S. aureus, generate antimicrobial metabolites and enhance innate immunity, lowering bacterial load and inflammation [14,17]. Through gut-skin axis, they regulate systemic immunity and block circulating inflammatory mediators, ensuring healthy skin [13]. Clinical trials indicate that probiotics can prevent or at least postpone AD in high-risk infants and improve symptoms in children and adults, with certain strains like Lactobacillus rhamnosus GG proving especially effective [18,19]. Findings are inconsistent, however, based on strain specificity, dosage, timing of administration, timing (e.g., prenatal or postnatal) and individual factors (e.g., genetics, early microbiota) and thus standardized regimens must be utilized [9,15].

In light of the current limitations of traditional therapies and preliminary evidence for microbial therapies, probiotics represent a potential adjunct therapy for AD [9,15]. This review integrates current understanding regarding probiotic supplementation in adult AD, including mechanisms of action, clinical efficacy, tolerability and study limitations. Drawing on microbiological, immunological and clinical data, it aims to evaluate the therapeutic potential of probiotics and direct future studies towards maximizing patient benefit.

Materials and Methods

Research Question/Objective

This systematic review assesses the safety and effectiveness of probiotic supplementation for the management of Atopic Dermatitis (AD) in adults (≥18 years) and its ability to modulate underlying pathophysiological mechanisms. The primary outcomes are clinical endpoints (e.g., AD severity, quality of life), immunomodulatory effects (e.g., cytokine modulation) and microbiome changes (e.g., Staphylococcus aureus colonisation). The review gathers January 1, 2000, to June 3, 2025, peer-reviewed literature excluding pediatric studies to fill an evidence gap in adults.

Research Design

The review adopted Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines with a mixed-methods strategy of combined qualitative narrative synthesis and quantitative meta-analysis where possible. The design was used to allow heterogeneity in study designs and non-availability of high-quality Randomized Controlled Trials (RCTs) among adults, to generate a solid synthesis of heterogeneous evidence.

Study Population and Sampling

The population included in the study was peer-reviewed literature, i.e., clinical trials, systematic reviews, meta-analyses and observational studies, in adults (≥18 years) with AD diagnosed by clinical criteria (e.g., Hanifin and Rajka) or by validated instruments [6]. One pre-specified inclusion criterion was fulfilled by studies obtained through a purposive sampling approach. Primary human or animal subjects were not included; the sample consisted of published literature retrieved by systematic searching that had a focused range of 50-100 studies to ensure maximum inclusivity.

Search Strategy

• Database Searched: PubMed, Scopus, Cochrane Library and Web of Science
• Search Terms and Keywords: “Atopic Dermatitis” OR “Eczema,” “Probiotics” OR “Lactobacillus” OR “Bifidobacterium” OR “Saccharomyces” OR “Probiotic strains,” “Microbiome” OR “Microbiota” OR “Gut-skin axis” OR “Skin microbiome,” “Immune modulation” OR “Immune response” OR “Inflammation” OR “Cytokine regulation,” “Clinical outcomes” OR “Treatment” OR “Therapy” OR “Disease severity” OR “Quality of life,” “Randomized Controlled Trial” OR “RCT” OR “Cohort study” OR “Case-control study” OR “Observational study”
• Boolean Operators: “AND,” “OR” were used to limit searches (e.g., “Atopic Dermatitis AND Probiotics”)
• Filters: English-language literature, dates from January 1, 2000, to June 3, 2025, with a preference for RCTs, systematic reviews and meta-analyses, with observational studies as an addition
• Manual Search: Included were hand-screened studies lists and reference lists of relevant reviews. Grey literature such as conference proceedings, theses and clinical trial registries (e.g., ClinicalTrials.gov, WHO International Clinical Trials Registry Platform) were also searched with a view to limiting publication bias

Inclusion and Exclusion Criteria

• Inclusion Criteria: Trials were considered for inclusion if they: (1) enrolled adults (≥18 years) with AD, (2) compared oral or topical probiotic supplementation (e.g., Lactobacillus, Bifidobacterium) as a primary or secondary therapy, (3) included a control group (e.g., placebo, standard therapy), (4) employed outcomes such as AD severity (e.g., SCORAD, EASI), immune modulation (e.g., cytokine levels), microbiome composition, quality of life (e.g., DLQI) or side effects [7] and (5) were RCTs, cohort studies, case-control studies, observational studies, systematic reviews or meta-analyses
• Exclusion Criteria: The following studies were excluded which: (1) were entirely pediatric in scope, (2) did not have measurable AD-related outcomes, (3) were not in English with inadequate translation, (4) contained methodological defects (e.g., ambiguous intervention or findings) or (5) were duplicate or non-peer- reviewed

Study Selection Process

Two independent reviewers used a multi-stage selection process to screen titles and abstracts against inclusion/exclusion criteria, with discussion or a third reviewer used to resolve disagreement. Full-text evaluation followed, reasons for exclusion recorded (e.g., inappropriate population, poor data). A PRISMA flowchart was used to monitor identified studies, screened, included and excluded. Remote online database data collection was between January and June 2025, with additional manual searches.

Data Management and Synthesis

• Data Extraction: Structured form collected study identifiers (e.g., authors, year, journal), design (e.g., RCT, cohort), participant information (e.g., age, gender, AD severity), intervention information (e.g., probiotic strain, dose, duration, route), outcomes (e.g., SCORAD scores, cytokine levels, DLQI), results (e.g., mean changes, p-values) and funding/conflicts of interest. Two reviewers extracted data independently and settled on disagreement by consensus.
• Data Storage: Data were saved in an encrypted password-protected database (e.g., REDCap) using a distinct identifier for each study
• Data Synthesis: Qualitative Synthesis: Narrative synthesis sorted findings by themes (e.g., clinical efficacy, immune modulation, safety), harmonizing effects and dissolving inconsistencies
• Quantitative Synthesis: Meta-analysis was performed on similar studies, estimating effect sizes (e.g., mean difference, odds ratio) with 95% CI on RevMan 5.4 or R. Heterogeneity was tested by I² statistic and Cochran’s Q test with subgroup analysis according to probiotic strain, dose and duration. Discrepancies were resolved through quality assessment and narrative explanation and conclusions drawn according to evidence strength

Variables and Measures

Independent variable was probiotic treatment (i.e., strain, dose, duration, route). Dependent variables were severity of AD (i.e., SCORAD, EASI), immune modulation (i.e., cytokine level, IgE, eosinophil count), skin microbiota community structure (i.e., microbial diversity, S. aureus colonization), quality of life (i.e., DLQI) and adverse effects [7]. Control variables were study design, participant demographics and comparator interventions (i.e., placebo, standard treatment). Variables were measured with standardized severity scores and laboratory tests (e.g., ELISA for cytokines).

Quality Evaluation

• RCTs: Evaluated through the Cochrane Risk of Bias 2.0, considering randomization, blinding and selective report
• Observational Studies: Evaluated through the Newcastle-Ottawa Scale, considering selection, comparability and outcome measurement
• Systematic Reviews/Meta-Analyses: Evaluated through AMSTAR 2 to assess methodological quality. Evidence was graded through quality ratings and recorded biases

Reliability and Validity

Reliability was attained with double-review procedures and inter-rater agreement (e.g., Cohen’s kappa >0.8) and standardized extraction forms. Internal consistency within multi-item scales was calculated using Cronbach’s alpha in quantitative analysis. Validity was optimized by pilot-testing the search strategy, triangulation of findings by study design and PRISMA guidelines adherence for reducing bias.

Ethical Considerations

Since secondary analysis, Institutional Review Board (IRB) approval was unnecessary. Ethical considerations first considered transparency in the sense that source studies were expected to be sufficiently ethically cleared. Conflict of interest (industry sponsorship, for instance) in source studies was declared and anonymization of data occurred at synthesis. The inclusion of grey literature conformed to ethical requirements to prevent misrepresentation.

Limitations of the Review

Homogeneity among study design, probiotic strains and doses were treated using subgroup analysis and narrative synthesis. Small numbers and small amounts of well- documented RCTs were dealt with by the use of observational data and comprehensive quality assessment. Short follow-up periods minimized analysis of long-term effect, partially balanced by recent updating of trials. Publication bias was minimized by inclusion of grey literature and examination of funnel plots (e.g., Egger’s test). Grey literature gaps and English-language restrictions were accommodated, weighed against expert searches and hand searching, with restrictions clearly defined to inform future studies.

Results

This article integrates data from 13 probiotic supplementation studies of Atopic Dermatitis (AD) in adults, consisting of 7 studies (224 patients) with Lactobacillus spp. (follow-up: 8 weeks to 84 days) and 6 trials (878 patients) with probiotic products (follow-up: 8 weeks to 12 months). Outcomes are described through narrative synthesis and two combined tables based on clinical effects (e.g., SCORAD, EASI, DLQI), immunological activities, microbiome modulation, quality of life and safety.

Overview of Included Studies

The review encompasses 13 trials: 7 that compared single or double-strain Lactobacillus spp. supplements and 6 that compared multi-strain probiotic mixes, typically with a combination of Lactobacillus and Bifidobacterium species, with prebiotics or postbiotics added in a minority. Follow-up ranged from 8 weeks to 12 months, enabling short- and medium-term effects to be measured. Primary outcomes were AD severity (e.g., SCORAD, EASI), immunological markers (e.g., cytokines, IgE, T-cell ratios), microbiome alterations (e.g., gut species richness, S. aureus colonization), quality of life (DLQI) and safety (adverse events).

Clinical Outcomes, Immunological Effects and Safety