Background Functional dyspepsia (FD) is a ‘gut-brain interaction disorder’ originating from the stomach and duodenum. Conventional treatment methods show limited efficacy and are prone to intestinal dysbiosis. This study introduced the concept of ‘gastric diseases treatment via gastric microbiota,’ aiming to investigate the potential of human gastrogenic Lactobacillus LPF-01 in the control of FD.

Methods A single-arm clinical trial involving 26 patients with FD was conducted. Participants received regular oral administration of LPF-01 for 8 weeks. The primary outcomes included gastrointestinal symptom rating scale (GSRS), quality of life scores (QOL), and emotional scores before and after treatment. FD rat model was built and animal experiments were conducted. The gut microbiota and serum neurotransmitter were assessed using 16S rRNA sequencing technology and LC-MS, respectively. QPCR, Western blot, immunohistochemistry and ELISA were used to interrogate the molecular basis.

Results After 8 weeks of LPF-01 treatment, the GSRS score (37.54 vs. 21.23, P=0.0012), QOL score (23.54 vs. 12.77, P=0.0019) and emotional scores (5±3 vs 2.2±1.6, P<0.05) decreased in the subjects significantly. Similar clinical trial results were replicated in animal models through behavioral tests. LPF-01 treatment was determined to elevate the abundance of Lactobacillaceae and reduce the abundance of Helicobacteraceae. LC-MS analysis revealed that LPF-01 attenuated kynurenine production, inhibiting the conversion of tryptophan to the downstream neurotoxic substance. Consistently, after LPF-01 intervention, expression levels of corresponding enzymes in the tryptophan-kynurenine pathway (indoleamine 2,3-dioxygenase 1 (IDO1), kynurenine 3-monooxygenase (KMO), kynureninase (KYNU)) were decreased in the gastric antrum and brain tissues, while no significant differences were detected in colon tissue.

Conclusions Human gastrogenic Lactobacillus LPF-01 emerges as a promising therapeutic approach for FD by gut microbiota regulation and kynurenine metabolism pathway.