Efficacy of Lacticaseibacillus rhamnosus GG in the treatment of canine atopic dermatitis: A randomized controlled study

Abstract

Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease driven by immune dysregulation. Recent studies suggest a connection between the gut microbiome and skin health, highlighting the potential for probiotics to manage dermatological conditions. Therefore, this study aimed to evaluate the effectiveness of Lacticaseibacillus rhamnosus GG in reducing skin lesion severity and pruritus in dogs with mild to moderate CAD. Forty dogs were randomly divided into two groups: one receiving L. rhamnosus GG (1 × 10⁹ CFU/day) and the other a placebo for 90 days. All dogs maintained their standard oclacitinib therapy. Clinical outcomes were assessed using the CADESI-04 scale and a pruritus visual analogue scale (pVAS) at days 0, 45, and 90. Significant reductions in CADESI-04 scores were observed in the probiotic group compared to the placebo (p < 0.01), while pVAS scores improved only in the probiotic group. No adverse effects were reported. These findings support the potential of L. rhamnosus GG to enhance treatment outcomes in dogs with atopic dermatitis.

Supplementary Information

The online version contains supplementary material available at 10.1007/s42770-025-01767-x.

Introduction

Canine atopic dermatitis (CAD) is a hereditary inflammatory skin disease, primarily driven by T-cells and characterized by persistent pruritus. It involves complex interactions among skin barrier defects, allergen sensitivity, and microbial imbalance [1]. Typically emerging in young dogs, this condition is often seasonal but tends to progress into a chronic issue [2]. More recently, a connection between atopic manifestations in dogs and the intestinal microbiome became evident [3]. The microbiome is a key regulator of the immune system as it maintains homeostasis through bidirectional communication with various tissues and organs [4]. Recently, the gut-skin axis hypothesis proposes that gut dysbiosis can induce systemic immune dysregulation, characterized by increased Th2-mediated inflammation, impaired epithelial barrier integrity, and altered production of regulatory metabolites, all of which contribute to the pathogenesis and exacerbation of dermatological conditions such as CAD [5]. One way to positively influence the gut microbiome is through the use of probiotics, which are defined as live microorganisms that, when administered in adequate quantities, confer a health benefit on the host [6]. Lacticaseibacillus rhamnosus GG is a probiotic strain with remarkable abilities to survive gastric acidity, adhere to mucosal surfaces and modulate immune responses through the production of bioactive factors, favoring an anti-inflammatory profile. In human medicine, L. rhamnosus GG has been effective in reducing allergic disease severity, including atopic dermatitis [7]. In dogs genetically predisposed to atopic dermatitis, L. rhamnosus GG administration from early life decreased serum allergen-specific IgE levels and skin reactivity, indicating a potential modulatory effect on disease pathophysiology [8]. Due to its potential effects, this study aims to evaluate the effectiveness of oral L. rhamnosus GG to reduce the severity of skin lesions and pruritus in dogs with mildly to moderately CAD.

Materials and methods

The research was conducted on dogs residing in three cities within the state of Rio Grande do Sul, Brazil. Ethical approved was received from the Ethics Committee for Animal Use of the Universidade de Caxias do Sul (approval number: 0008/2022). The sample size was estimated using the G Power 3.1.9.2 calculator program from the University of Kiel, Germany (http://www.gpower.hhu.de/).

The inclusion criteria were a clinical history of chronic non-seasonal pruritus and a diagnosis based on Canine Atopic Dermatitis Extent and Severity Index (CADESI-4), a validated clinical scoring system that evaluates erythema, lichenification, excoriation, and alopecia across 20 body sites with scores ranging from 0 to 3, yielding a maximum of 180 [9, 10]. Only patients with CADESI-04 ≤ 59 were included in the study. Inclusion also required a pruritus pVAS score of at least 1. Additionally, thorough physical and cytological examinations of the skin and ears were conducted to exclude microbial infections. Subjects with concomitant endocrinopathies or neoplasms, as well as those who had undergone treatments involving cyclosporine, immunotherapy, oral or topical corticosteroids within the previous 4-month period, and systemic or topical antibiotics within the previous 4 weeks, were excluded. No patient has received immunotherapy in at least one year. All dogs were required to have received oclacitinib (Apoquel; Zoetis^®) (0.4–0.6 mg/kg every 24 h) for a minimum period of 4 months prior to enrolment. Concomitant therapies, including topical therapies (bathing, ear cleaning solutions), preventive management of ectoparasites, and nutritional intake were to remain unchanged, along with the administration of oclacitinib during the 12-week duration of the study.

In total, forty dogs (sixteen males and twenty-four females) were enrolled in this study. The average age was 6.6 ± 3.4 years old. The included breeds were Shih Tzu (n = 24), mixed breed (n = 4), Yorkshire terrier (n = 3), German Spitz (n = 1), Maltese (n = 1), French bulldog (n = 2), miniature poodle (n = 2), Pekingese (n = 2), and Shar Pei (n = 1). The participants were randomly allocated into two groups of 20 individuals each. The test group received Lacticaseibacillus rhamnosus GG (ATCC 53103) at a dose of 1 × 10⁹ colony-forming units (CFU) per day, while the placebo group received an identical dose of an inert compound (Dilucap Hygro^®, Brazil). Both probiotic and placebo were administered orally in opaque gelatin capsules that were identical in shape, color, and taste, ensuring proper blinding throughout the trial. The dosage of L. rhamnosus GG was selected based on previous studies in veterinary medicine, where probiotic doses ranging from 10⁸ to 10¹⁰ CFU/day have been shown to effectively modulate the gut microbiota and immune response in dogs without adverse effects​ [11]. L. rhamnosus GG or placebo were administered orally at night, two hours after meal, every 24 h for 90 days. The dogs were evaluated on days zero (D0), forty-five (D45), and ninety (D90). Placebo and L. rhamnosus GG were formulated by a compounding pharmacy, administered in identical capsules (0.01 g each). The CADESI-04 scale was assessed by the same clinic and pruritus was scored by owners using a pruritus visual analogue scale (pVAS) on evaluated days [10, 12]. Statistical analyses were performed using SPSS Statistics (IBM, version 26.0). For all statistical analyses, a significance level of 5% (p ≤ 0.05) was adopted. The normality of the data was confirmed using the Shapiro-Wilk test. Given the normal distribution, paired Student’s t-tests were used to analyze intra-group differences (pre- and post-treatment), and independent samples Student’s t-tests were used to analyze inter-group differences at each evaluation point (D0, D45, and D90). Baseline CADESI-04 and pVAS scores were compared between groups at D0 to confirm the absence of significant differences prior to treatment initiation.

Results

Significant changes in CADESI-04 scores were observed in the test group receiving L. rhamnosus GG, with a reduction from 16.10 ± 6.66 on day 0 (D0) to 10.80 ± 5.81 by day 45 (D45) and 9.60 ± 5.60 by day 90 (D90) (p < 0.01 for both) (Fig. 1). In the placebo group, scores decreased from 18.95 ± 8.03 on D0 to 14.55 ± 5.8 by D45 (p = 0.013) but slightly increased to 15.15 ± 10.82 by D90 (p = 0.157). There was no significant difference between the two groups at the beginning of the study (16.10 ± 6.66 in the test group compared to 18.95 ± 8.03 in the placebo group, p > 0.05). However, a significant reduction in the probiotic group was identified at the second evaluation (D45) (difference of 3.75 ± 1.84, p = 0.049) and at the third evaluation (D90) (difference of 5.55 ± 2.72, p = 0.049). Regarding pVAS scores, significant changes were observed only in the probiotic group, with a reduction from 5.39 ± 1.6 on D0 to 4.07 ± 1.84 by D45 (p < 0.01) and no significant change between D45 and D90. In the placebo group, scores changed from 4.87 ± 1.64 on D0 to 5 ± 1.45 by D45 (p = 0.738) and 4.52 ± 1.88 by D90 (p = 0.514). In this group, the initial score on D0 was 4.87 ± 1.64, increasing to 5 ± 1.45 by D45 (p = 0.738) and decreased to 4.52 ± 1.88 by D90 (p = 0.514, compared to D0). When comparing pVAS scores between the two groups, no significant differences were observed at any of the evaluation points. Throughout the study, no adverse effects were observed in any of the participating dogs. The complete results and data for all animals are provided in the supplementary material.

Fig. 1.

CADESI − 04 score and pVAS assessed on days zero (D0), forty-five (D45) and ninety (D90) of the placebo group (blue) and test group (purple). The box plot graphic represents the lowest and higher data in the data set (upper and lower line), the lower quartile and upper quartile (boxes), median (main line) and mean (x). The symbol (*) indicates statistical differences between placebo group and test group (p < 0.05)

Discussion

To the authors’ knowledge, this is the first study to report a potentially beneficial effect from the use of L. rhamnosus GG combined with oclacitinib in the management of CAD. The results demonstrate a reduction in CADESI-04 scores in both the L. rhamnosus GG plus oclacitinib group and placebo group (oclacitinib only). However, the group receiving the probiotic exhibited a statistically significant greater reduction in CADESI-04 scores compared to the placebo group at both D45 and D90. Regarding pruritus, a significant reduction in pVAS scores was observed only in the probiotic group. This improvement aligns with the gut-skin axis hypothesis, indicating that probiotics may influence dermatological conditions through immune modulation and gut microbiome balance. Moreover, a decrease in allergen-specific IgE levels has been previously reported in dogs treated with L. rhamnosus GG, providing further support for the immunomodulatory potential of this strain [8].

Several factors contributed to the selection of L. rhamnosus GG for this study. This probiotic strain has been linked in earlier studies toclinical improvements in dogs with CAD [7, 13, 14], including reductions in pruritus and skin lesion scores. In addition to its safety profile, L. rhamnosus GG exhibits immunomodulatory properties such as the stimulation of anti-inflammatory cytokines (e.g., IL-10) and regulation of Th1/Th2 responses. Moreover, it enhances epithelial barrier function, modulates intestinal permeability, and promotes the hydrolysis of antigenic peptides, contributing to gut and systemic immune homeostasis [8]. These combined effects suggest its potential as a valuable adjunct therapy in immune-mediated dermatologic diseases like CAD.

A notable strength of this trial was the methodological rigor in minimizing potential confounding variables. All dogs remained on a stable oclacitinib regimen and maintained a consistent diet, reducing external variability. Randomization and blinding procedures were strictly adhered to, increasing the internal validity and reproducibility of the findings.

However, despite these methodological strengths, certain limitations should be acknowledged when interpreting the results. While the findings of this study suggest that oral supplementation with L. rhamnosus GG may offer additional clinical benefits in the management of mild to moderate atopic dermatitis in dogs receiving oclacitinib, caution is warranted in extrapolating these results. All animals enrolled in the study were under stable oclacitinib therapy and presented with mild to moderate clinical signs. For ethical reasons, a control group receiving only the probiotic without oclacitinib was not included, as withholding effective anti-inflammatory treatment in symptomatic animals would contravene current veterinary welfare standards. Consequently, it remains unknown whether similar effects would be observed in dogs with more severe disease, in those managed without immunomodulatory therapy, or under alternative pharmacological regimens. Future studies should assess the probiotic’s efficacy in broader clinical contexts and explore its potential as a monotherapy in milder cases or during remission phases, where withdrawal of standard drugs may be ethically feasible. While the findings of this study suggest that oral supplementation with L. rhamnosus GG may provide additional benefits in the management of mild to moderate CAD in dogs receiving oclacitinib, caution is warranted when generalizing these results. The study population was limited to dogs on stable oclacitinib therapy and with mild to moderate clinical severity. Therefore, it remains to be determined whether similar effects would be observed in dogs with severe disease, those untreated with immunomodulatory therapies, or those managed with other pharmacological protocols. Future studies should evaluate the efficacy of L. rhamnosus GG across diverse clinical settings and investigate its potential as a standalone adjunctive therapy.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

The authors declare that no funding was received for this study.

Declarations

Conflict of interest

The authors declare no conflicts of interest relevant to this article.