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Background Functional dyspepsia (FD) is a common disorder originating from the gastroduodenal region, for which no curative treatment currently exists. Traditional microecological therapies based on intestinal-derived strains or fermented foods often face challenges in gastric colonization. Given the dysbiosis of the upper gastrointestinal microbiota in FD patients, this study focuses on the gastric microbiome and utilizes organoid models to explore the therapeutic potential of gastric-derived probiotics for FD.Methods Multiple potential probiotic strains with high acid tolerance and efficient gastric colonization ability were isolated from the human stomach. Human gastric and intestinal organoid models were established and co-cultured with these strains. Strains with potential therapeutic effects for FD were screened in vitro by measuring changes in neurotransmitter levels within the co-culture systems.Results A gastric-derived strain, Lactobacillus paragasseri LPG-9, exhibiting strong acid tolerance and colonization capacity, was selected. Metabolites in the supernatant following LPG-9 co-incubation with gastric organoids were significantly enriched in the tyrosine metabolic pathway. LPG-9 specifically inhibited the conversion of levodopa to dopamine, an effect demonstrating significant site selectivity. Co-culture with gastric organoids led to significant levodopa accumulation and decreased dopamine levels, whereas this effect was absent in the intestinal organoid model.Conclusions Dopamine is known to inhibit gastrointestinal motility. This study reveals that a specific gastric-derived probiotic can locally regulate dopamine metabolism within the stomach, influencing upper gastrointestinal neurotransmitter homeostasis. This finding provides a novel theoretical basis and a potential probiotic resource for developing therapeutic strategies for functional dyspepsia targeting the gastric microbiome.