Search Results (263)

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by type 2 inflammation, including M2 macrophage infiltration. Baicalein is a flavonoid with anti-inflammatory properties. This study aimed to investigate the therapeutic effect of baicalein in a papain-induced eosinophilic rhinosinusitis model and to determine whether it acts through arachidonate 15-lipoxygenase (ALOX15)-dependent M2 macrophage function. Clinical nasal samples from controls, non-eosinophilic CRSwNP (neCRSwNP), and eCRSwNP were analyzed for ALOX15 expression and localization. THP-1 cells were differentiated and polarized toward M2 macrophages, and the effects of baicalein on ALOX15 expression, lipid peroxidation, cytokine secretion, and transcriptomic profile were examined. The ALOX15 inhibitor PD146176 was used for target validation. A murine eosinophilic rhinosinusitis model was established by intranasal papain instillation, followed by baicalein treatment. Mucosal inflammation, IgE levels, proteoglycan 2 (PRG2)/ALOX15 expression, and immune cell infiltration were evaluated. ALOX15 was upregulated in eCRSwNP tissues and localized to CD68⁺CD206⁺ M2 macrophages. In vitro, M2 polarization increased ALOX15 expression and lipid peroxidation. Baicalein suppressed ALOX15 expression, lipid peroxidation, and the secretion of CCL22, CCL2, CXCL12, FGF-2, and IL-15. PD146176 produced similar effects, and baicalein showed no additional effect after ALOX15 blockade. RNA sequencing revealed transcriptional remodeling in M2 macrophages after baicalein treatment. In vivo, papain increased ethmoid sinus mucosal thickening, serum IgE, PRG2/ALOX15 positive cells, and infiltration of CD45⁺ immune cells, CD170⁺ eosinophils, F4/80⁺ macrophages, and B220⁺ B cells. Baicalein significantly alleviated all these pathological changes. In conclusion, baicalein attenuates papain-induced eCRSwNP-like inflammation by inhibiting lipid peroxidation and ALOX15-associated M2 macrophage secretory function. The ALOX15/M2 macrophage axis may represent a potential therapeutic target for eCRSwNP. Full article

Objectives: Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory upper airway disease. Despite a higher radiological disease burden in males, clinical CRS diagnoses are disproportionately registered in females, suggesting systematic underdiagnosis in young men. The 22-item Sinonasal Outcome Test (SNOT-22) represents the reference patient-reported outcome measure (PROM) for sinonasal symptom burden. This study aimed to determine the prevalence of sinonasal symptom burden and to identify associated clinical, laboratory, and lifestyle parameters in a large cohort of young male adults. Methods: In this prospective cross-sectional study, 500 young male adults underwent, as part of the conscription examination, standardized assessment including the SNOT-22, spirometry (FEV₁%), whole blood count (eosinophils), and serum CRP. SNOT-22 scores were categorized as none (0–20), moderate (21–50), and severe (>50). Associations were analyzed using Spearman correlation, Mann–Whitney U, and Chi² tests. Results: The mean SNOT-22 score was 18.8 (SD 15.2; range 0–73). A total of 38.2% of participants scored ≥21, indicating at least moderate sinonasal symptom burden. SNOT-22 correlated significantly with CRP (r = 0.117, p = 0.009) and inversely with relative FEV₁% (r = −0.103, p = 0.022). Eosinophils showed a numeric gradient across SNOT-22 categories (3.08% vs. 3.31% vs. 3.56%) without reaching significance. Conclusions: More than one third of young male adults reported significant self-reported sinonasal symptom burden. Symptom severity was associated with systemic inflammatory markers and reduced pulmonary function, supporting the unified airway concept. These findings support the utility of SNOT-22 as a low-threshold assessment tool for self-reported sinonasal symptom burden in preventive health examinations. Full article

Existing diagnostic markers of sepsis indicate already developed inflammatory complications, whereas predictors enable preoperative identification of high-risk patients for preventive measures. This study aimed to evaluate the prognostic value of preoperative inflammatory biomarkers for postoperative complications in cardiac surgery patients. Preoperatively, we assessed age, body mass index, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), complete blood count with hematological indices including neutrophil-to-lymphocyte ratio (NLR), serum cytokines, HIF1A (hypoxia-inducible factor 1-alpha), and EPAS1 (endothelial PAS domain protein 1) expression in peripheral blood leukocytes. During surgery, cardiopulmonary bypass time, myocardial ischemia time, and blood loss were recorded. Postoperatively, complications, intensive care unit (ICU) stay, and total hospitalization were documented. No differences were found in non-modifiable risk factors or perioperative parameters between groups, except for longer ICU stay in the complications group. Preoperatively, absolute neutrophil count and NLR were higher in patients without complications, while eosinophil count, HIF1A expression, and HIF1A/EPAS1 ratio were higher in those with it. The HIF1A/EPAS1 ratio demonstrated the best diagnostic characteristics. Thus, preoperative predictors of postoperative inflammatory complications include low neutrophil count and NLR, as well as high HIF1A expression and HIF1A/EPAS1 ratio. These markers may facilitate early risk stratification and preventive strategies before surgery. Full article

Background/Objectives: Metabolic syndrome (MetS) and dry eye disease (DED) share inflammatory mechanisms, yet few studies have examined objective tear function and serum inflammatory markers together in this population. The aim of this study was to compare tear function tests and a panel of systemic inflammatory indices between patients with MetS who did and did not have DED. Methods: This observational comparative study enrolled 104 adults with MetS (52 MetS-DED and 52 MetS-nonDED), with group-level comparability for age and sex. All participants underwent ophthalmologic evaluation, including the Ocular Surface Disease Index (OSDI), the Schirmer I test, and fluorescein tear break-up time (TBUT). DED was defined by a mean Schirmer I value of ≤5 mm/5 min. Routine blood tests were used to derive the neutrophil-, platelet-, monocyte-, and eosinophil-to-lymphocyte ratios (NLR, PLR, MLR, ELR), the neutrophil–lymphocyte–platelet ratio (NLPR), the C-reactive protein (CRP)-to-albumin ratio, and the monocyte-to-high density lipoprotein cholesterol (HDL) ratio. Between-group comparisons, receiver operating characteristic (ROC) analysis with Youden’s index, and age- and sex-adjusted binary logistic regression were performed. Results: TBUT and Schirmer I values were significantly lower in the MetS-DED group, whereas OSDI scores did not differ between the groups. NLR, MLR, NLPR, CRP, and the CRP-to-albumin ratio were significantly higher in MetS-DED patients (all p < 0.05), while classic metabolic parameters were comparable. ROC analysis revealed statistically significant but weak-to-modest discriminatory ability (areas under the curve (AUCs) 0.617–0.652). In age- and sex-adjusted models, MLR (odds ratio (OR) = 1.072 per 0.01 unit, p = 0.046), the CRP-to-albumin ratio (OR = 1.062 per 0.01 unit, p = 0.011), and NLPR (OR = 1.123 per 0.001 unit, p = 0.038) remained significantly associated with MetS-DED. Conclusions: Among individuals with MetS, the presence of DED was accompanied by impaired tear function and a more pronounced systemic inflammatory profile despite similar metabolic parameters. However, the modest discriminatory performance and borderline adjusted associations indicate that these findings should be regarded as preliminary signals rather than evidence supporting the clinical use of these markers for screening or risk identification. Full article

Background/Objectives: Kimura disease is a rare, chronic immune-mediated disorder that classically produces painless head-and-neck masses, regional lymphadenopathy, blood eosinophilia, and a raised serum immunoglobulin E (IgE). Almost all reported patients are young East Asian men, and the condition is seldom encountered in the Middle East, where it is easily mistaken for lymphoma or another eosinophilic disorder. We describe a histologically confirmed case in a Saudi adolescent and review the literature to compare treatment strategies and outcomes across populations. Methods: We documented the clinical course, laboratory profile, histopathological findings, and 15-month outcome of the patient, and searched PubMed for reported cases of Kimura disease, with emphasis on pediatric and non-Asian series. Results: A 16-year-old boy presented with a one-year history of painless right cervical swelling, constitutional symptoms and striking eosinophilia (36%; absolute eosinophil count 6.5 × 10⁹/L). Hematological malignancy was excluded through bone-marrow examination, flow cytometry and molecular studies. Excisional lymph node biopsy revealed the diagnostic triad—reactive follicular hyperplasia, a dense eosinophilic infiltrate with microabscesses, and vascular proliferation—together with IgE-positive immunostaining. Complete remission followed surgical excision alone and was maintained at 15 months without systemic corticosteroids. Conclusions: Kimura disease occurs well beyond its traditional geographic boundaries and belongs in the differential diagnosis of eosinophilia accompanied by lymphadenopathy. Although corticosteroids remain the mainstay for extensive disease, relapse on tapering is common, whereas complete excision can secure lasting remission in localized pediatric disease while sparing patients from steroid-related toxicity. Full article

This study evaluated the immunomodulatory activity of live Lacticaseibacillus paracasei Yb in vitro and compared response patterns associated with practical L. paracasei Yb formulation formats in an ovalbumin (OVA)-induced allergic airway inflammation mouse model. In vitro, live L. paracasei Yb increased TNF-α production in RAW 264.7 macrophages at 2 × 10⁶ to 5 × 10⁷ CFU/mL, increased IL-1β only at 5 × 10⁷ CFU/mL, and increased IL-10 at 1 × 10⁷ and 5 × 10⁷ CFU/mL. In splenocytes, L. paracasei Yb increased TNF-α, IFN-γ, and IL-10 compared with untreated controls, although these responses did not show a simple concentration-dependent pattern. In vivo, BALB/c mice received fresh L. paracasei Yb yogurt (YG), freeze-dried yogurt (YG-FD), or bacterial powder (BP) for 53 days. Compared with the OVA-sensitized Negative control group, YG and BP did not significantly reduce serum total IgE or OVA-specific IgE, and airway responsiveness and BALF eosinophils showed limited or non-significant changes. In contrast, YG and BP significantly reduced lung inflammation scores (Negative control, 6.86 ± 1.57; YG, 5.13 ± 0.83; BP, 4.50 ± 0.55) and ConA-stimulated splenocyte IL-4 secretion (Negative control, 1168.43 ± 553.34 pg/mL; YG, 589.84 ± 233.54 pg/mL; BP, 472.28 ± 186.44 pg/mL). These findings suggest that practical formulation conditions may shape selected preclinical immunological and histopathological responses to L. paracasei Yb. Further studies incorporating CFU-matched dosing, probiotic-free yogurt controls, and mechanistic validation are required before clinical relevance in asthma can be inferred. Full article

Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m², and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease. Full article

Food-induced anaphylaxis (FIA) is a life-threatening allergic reaction, while wheat-dependent exercise-induced anaphylaxis (WDEIA) is triggered by wheat ingestion plus cofactors. To elucidate their differences, we profiled serum extracellular vesicle (EV) proteomes from 240 participants, including WDEIA, FIA, oral allergy syndrome (OAS), and healthy controls. All blood samples were obtained at least one month after the most recent acute allergic reaction, using TMT-based LC-MS/MS with ELISA validation. A total of 583 EV proteins were confidently identified, revealing distinct immune features. Compared with controls, EV-derived C1-inhibitor (C1-INH) significantly decreased in both WDEIA and FIA, showing diagnostic potential for systemic anaphylaxis. Seventy-six proteins differed between WDEIA and FIA, with reduced apolipoprotein E (APOE) in FIA and elevated eosinophil cationic protein (ECP) in WDEIA, both exhibiting good discriminatory power. These findings indicate that serum EV proteomics can reveal unique immune signatures and identify C1-INH, APOE, and ECP as potential biomarkers distinguishing food-related anaphylaxis subtypes. Full article

This study aimed to investigate the anti-allergic potential of the ethyl acetate fraction (EtOAc) from Phyllanthus amarus using an ovalbumin (OVA)-induced allergic mouse model and in vitro RBL-2H3 mast cell assays. The EtOAc fraction was characterized by high total phenolic and flavonoid contents, reaching 261 ± 18 mg GAE/g EtOAc fraction and 86 ± 7 mg QE/g EtOAc fraction, respectively. It was found that EtOAc fraction significantly reduced histamine release up to 43.3% and suppressed reactive oxygen species (ROS) production from FcɛRI-mediated mast cell activation at a concentration treatment of 200 µg/mL. Furthermore, EtOAc fraction decreased interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) release up to 94.2 pg/mL and 195.6 pg/mL, respectively. In the OVA-induced allergic mouse model, EtOAc fraction treatment markedly lowered sneezing frequency and serum IgE and histamine levels by approximately 50% at a dose treatment of 50 mg/kg. In addition, histopathological analysis revealed that the EtOAc fraction significantly alleviated inflammatory cell infiltration, particularly eosinophils, in lung tissue. Accordingly, the results highlight the potential of EtOAc fraction from P. amarus as a natural candidate for managing allergic diseases. Full article

Background and aims: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease among children. Our study aimed to evaluate the prevalence of hypogammaglobulinemia among pediatric patients with AD and to characterize the clinical and laboratory findings of patients diagnosed with AD and hypogammaglobulinemia. Method: The electronic files of 1850 patients aged 0–18 years diagnosed with AD between 2020 and 2022 in the Pediatric Immunology and Allergy Clinic of Bursa Medical Faculty City Hospital were retrospectively analyzed. During this period, all patients newly diagnosed with atopic dermatitis at our clinic were systematically screened for their serum immunoglobulin (Ig) levels (IgG, IgA, and IgM) at the time of initial presentation. We included 200 AD patients with hypogammaglobulinemia. Disease severity was classified using the Scoring Atopic Dermatitis (SCORAD) index. Multivariate logistic and linear regression analyses were performed to identify independent determinants of disease severity, considering age, sex, eosinophil counts, total IgE, food allergies, and baseline immunoglobulin levels. Results: The prevalence of hypogammaglobulinemia among the 1850 screened children with AD was 10.8% (200/1850). Of the 200 patients included in this study, 128 (64%) were male, and 72 (36%) were female. The median age at first clinic presentation was 8 months (interquartile range (IQR) 25–75%: 5–16). According to the Scoring Atopic Dermatitis (SCORAD) index, AD severity was mild in 150 (75%) patients and moderate-to-severe in 50 (25%). Food allergy sensitization was present in 72 (36%) patients. Patients with moderate-to-severe AD had significantly lower IgG (300 vs. 374 mg/dL; p < 0.001; r = −0.346), IgA (10 vs. 14 mg/dL; p = 0.004), and IgM (38 vs. 51 mg/dL; p = 0.001) levels when compared with those with mild disease. Multivariate logistic regression confirmed that lower IgG was the only immunoglobulin independently associated with moderate-to-severe AD (OR = 1.97 per 100 mg/dL decrease; 95% CI: 1.15–3.39; p = 0.013), while food allergy was the strongest independent predictor of the SCORAD index (β = +11.97; p < 0.001). None of the patients received intravenous immunoglobulin (IVIG) treatment. Of the 142 patients who underwent serial serum immunoglobulin measurements, 56 (39%) achieved age-appropriate normal IgG levels, while hypogammaglobulinemia persisted in 86 (61%). Conclusions: We found a higher frequency of hypogammaglobulinemia in patients with AD in our study, as compared with previously reported rates of THI in children from the general pediatric population. Although our study showed an increase in IgG levels during the follow-up period in many patients, it emphasizes the need for long-term immunological monitoring, especially in patients with moderate-to-severe AD. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease increasingly prevalent in adults. Vitamin D plays an important role in regulating immune responses, cellular differentiation, and inflammation. Several single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been suggested as biomarkers of AD susceptibility and severity. The aim of this study was to investigate six SNPs in the VDR gene (rs3847987, rs731236, rs7975232, rs1544410, rs2228570, and rs11168293) and their association with AD and blood biomarkers. Genotyping was performed in 91 adult patients with AD and 102 controls using real-time polymerase chain reaction. The genotype and allele distributions did not differ significantly between AD patients and controls. However, the G and T alleles of VDR rs731236 and rs1544410 were more frequently detected in individuals with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/mL. In contrast, the VDR rs7975232 C allele appears to be associated with lower odds of having a serum 25(OH)D level above 30 ng/mL. In genotype-stratified analysis, the T allele of VDR rs11168293 was more prevalent among individuals with eosinophil counts of 300 cells/μL. These findings suggest that VDR polymorphisms may contribute to variability in vitamin D status and inflammatory responses in adults with AD. Full article

Porcine β-defensin 2 (pBD2) possesses broad-spectrum antimicrobial properties and is crucial for gastrointestinal mucosal repair. Lactic acid bacteria (LAB) serve as optimal vectors for exogenous protein delivery due to their high biosafety, intestinal colonization capacity, and ability to modulate gut microecology. In this study, we engineered a recombinant Lactobacillus paracasei strain (pPG-N1-pBD2/27-2) that efficiently secretes pBD2. In vitro, this recombinant strain significantly enhanced the proliferation and migration of porcine intestinal epithelial cells (IPEC-J2). In vivo, oral administration of pPG-N1-pBD2/27-2 markedly alleviated dextran sulfate sodium (DSS)-induced colitis in mice. This protective effect was evidenced by reduced Disease Activity Index (DAI) scores, prevention of colon shortening, and decreased colonic activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO), alongside normalized N-acetyl-β-D-glucosaminidase (NAG) levels. Histopathological analysis revealed that the treatment preserved mucosal architecture, including goblet cells and crypts, and fortified the physical barrier by upregulating tight junction proteins. Mechanistically, the recombinant strain suppressed the colonic iNOS/COX-2 inflammatory axis, decreased serum pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and elevated the anti-inflammatory cytokine IL-10. Furthermore, it restored systemic immune homeostasis by normalizing the proportions of splenic macrophages, T/B lymphocytes, and natural killer (NK) cells. In conclusion, pPG-N1-pBD2/27-2 mitigates colitis through a dual mechanism: reinforcing the intestinal physical barrier and rebalancing the innate–adaptive immune axis. These findings highlight the potential of pBD2-engineered probiotics as novel biological therapeutics for intestinal inflammatory diseases. Full article

Background: Diets composed of various components have been shown to influence inflammatory diseases such as asthma. While most studies have focused on fiber-rich diets to investigate their effects on the immune system and, consequently, on asthma, little is known about the impact of sugar-rich diets, particularly when such diets are consumed over short periods of time. Methods: To investigate the short-term effects of a sugar-rich diet on allergic airway inflammation, A/J mice were fed either a standard diet or a sugar-enriched diet and subsequently sensitized and challenged with ovalbumin or PBS. Airway inflammation was assessed by bronchoalveolar lavage (BAL) cell analysis, including eosinophil counts and cytokine levels (IL-4, TNF-α, IL-33), and by lung histology (H&E for inflammatory infiltrate and PAS for mucus). Serum IgE levels were also measured. In addition, glucose tolerance, visceral and subcutaneous adipose tissue mass, and inflammatory markers in visceral adipose tissue were evaluated. Results: Short-term consumption of a sugar-rich diet induced glucose intolerance and expansion of adipose tissue, particularly visceral fat, independent of ovalbumin sensitization. Gonadal adipose tissue analysis revealed a shift toward M1 macrophage polarization, characterized by elevated TNF-α, IL-6, and IL-1β, increased leptin levels, and reduced adiponectin. In OVA-sensitized mice, the sugar-rich diet significantly exacerbated eosinophil infiltration in BAL, increased IL-4, TNF-α, and IL-33, and enhanced PAS-positive mucus accumulation and inflammatory infiltrates in the lung. Moreover, total serum IgE was significantly higher in allergic mice fed the sugar-rich diet compared with allergic mice on the standard diet. Importantly, in non-sensitized mice fed the sugar-rich diet, no pulmonary inflammation was detected by BAL, demonstrating that HSD alone does not induce asthma but amplifies allergic responses when sensitization is present. Conclusions: Our findings demonstrate that short-term consumption of a sugar-rich diet is sufficient to exacerbate, but not initiate, allergic pulmonary inflammation. From a translational perspective, reducing dietary sugar intake may represent a valuable adjuvant strategy in the management of allergic asthma. Full article

Background/Objectives: The prevalence of allergic diseases has markedly increased in developed countries, with environmental and dietary factors considered important contributors. Folic acid is an essential micronutrient involved in one-carbon metabolism and DNA methylation, playing a key role in epigenetic regulation of immune function. Both high and low folate exposure have been associated with allergic outcomes, but the data on postnatal folate status in paediatric populations remain limited. This study aimed at assessing serum folate status in children with atopic diseases compared with children without chronic allergic disease in Croatia. Methods: This cross-sectional study included 292 paediatric patients from the University Hospital in Split and a paediatric primary care practice between January 2024 and January 2025. Serum folic acid concentrations were measured using electrochemiluminescence immunoassay. Additional laboratory parameters included vitamin B12, total IgE levels, and eosinophil counts. Demographic and clinical data were obtained from medical records. Statistical analyses included Chi-square tests, Mann–Whitney U tests, linear regression modelling, and analysis of covariance with statistical significance set at p < 0.05. Results: Folic acid deficiency was present in 66.4% of all participants. Children with atopic diseases were significantly more likely to have folate deficiency and had lower mean serum folate concentrations compared to children without allergic disease. There were no significant differences in folate levels between children with and without asthma. Lower folate levels were associated with higher IgE levels, higher eosinophil counts, and older age. When controlling for the effects of age on folic acid levels, the differences between participants with and without atopic diseases remained significant. Conclusions: Folic acid deficiency is highly prevalent among children in the Mediterranean region of Croatia and is significantly associated with atopic diseases and markers of allergic inflammation. These findings highlight a potential role of folate status in paediatric allergic disease and support the need for longitudinal studies to clarify causality and potential clinical implications. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease linked to epidermal barrier dysfunction, Th2-skewed immune polarization, and disrupted gut microbiota homeostasis. While probiotic interventions show promise in managing AD, the mechanisms governing strain-specific efficacy—particularly systemic modulation via the “gut–skin axis”—remaining to be fully elucidated. Methods: This study systematically compared the oral therapeutic effects of three Lacticaseibacillus rhamnosus strains (MG-A047, MG-A054, and LGG) in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Results: By integrating behavioral, histopathological, and serological assessments with 16S rRNA-based gut microbiota profiling and in vitro functional assays, this study offers a multidimensional evaluation of the strain-specific advantages and potential therapeutic mechanisms of three L. rhamnosus strains. The results demonstrate that MG-A054 most effectively alleviated cutaneous inflammation and pruritus, significantly reduced serum IgE and IL-4 levels, and attenuated epidermal hyperplasia and inflammatory cell infiltration (including mast cells and eosinophils). Mechanistically, this strain may directly inhibit hyaluronidase activity and mast cell degranulation, and specifically remodel the gut microbiota structure, thereby promoting a shift toward a healthier functional profile. Conclusions: These findings suggest that the superior efficacy of MG-A054 may be achieved through coordinated modulation of the gut–skin axis and related pathways. This study offers new mechanistic clues for understanding the strain-specific actions of probiotics and lays a preclinical foundation for the further development of MG-A054 as a potential targeted microecological therapy for AD. Full article