Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut-brain axis's importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of R0052 and R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME (Simulator of the Human Intestinal Microbial Ecosystem) model. The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey's tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Probiotic supplementation increased and , and decreased and . Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. The probiotic combination of R0052 and R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations-including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation-should be considered when interpreting the findings. Although the SHIME model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results.