CHENGDU, CHINA — A new study provides compelling evidence that the probiotic strain Lactobacillus johnsonii YH1136 can successfully prevent and mitigate schizophrenia (SCZ)-like behaviors in mice by acting on the microbiota-gut-brain axis (MGBA). The research, utilizing a multi-omics approach, links changes in gut microbes and specific metabolites directly to improvements in brain function and behavior.
Probiotic Reverses SCZ-like Behavior and Hyperactivity
The study established an SCZ-like mouse model using
MK-801, a noncompetitive N-methyl-D-aspartate receptor (NR) antagonist, which induces hyperactivity and social deficits resembling the positive and negative symptoms of SCZ in humans.
Mice that received the
L. johnsonii YH1136 probiotic (1×109 CFU daily for six weeks) demonstrated significant behavioral improvements:
- Psychomotor Hyperactivity: The probiotic significantly reduced the increased total distance traveled and mean velocity observed in the SCZ model mice, reversing the hyperactivity.
- Social Deficits: In the three-chamber sociability test (TCST), the probiotic-treated mice showed a significantly higher ratio of interaction time with novel mice, indicating improved sociability and preference for social novelty.
Key Mechanism: Tryptophan Metabolism Rebalanced in the Brain
The mechanism for these behavioral improvements was traced to the
tryptophan metabolic pathway in the hippocampus and prefrontal cortex (PFC), brain regions critical for cognition and memory.
- Neuroprotection: L. johnsonii YH1136 successfully mitigated the SCZ-induced significant decrease in the mRNA expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, indicating a neuroprotective role.
- Kynurenine Pathway Inhibition: The probiotic significantly reversed the upregulation of several rate-limiting enzymes in the kynurenine pathway, which converts tryptophan into kynurenine:
- Tryptophan 2,3-dioxygenase (TDO2) and Indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) levels were significantly increased in SCZ mice but decreased by YH1136 supplementation.
- Kynurenine aminotransferase 1 (KAT1) and KAT3 expression, which convert kynurenine to kynurenic acid, were significantly increased in SCZ mice and subsequently lowered by the probiotic.
This collective evidence suggests the therapeutic effect of
L. johnsonii YH1136 is tied to inhibiting the overactivation of the tryptophane-kynurenine-kynuuric acid metabolic pathway.
Gut Microbes and Metabolites Mediate the Axis
Analysis of the gut microbiota in the ileum was critical, as its structure was more significantly altered than that of the colon, implying the
ileum is more vulnerable to SCZ and probiotic intervention.
- Microbial Shifts: The probiotic therapy significantly modulated key genera in the ileum:
- Lactobacillus (genus including the intervention strain) abundance was significantly increased.
- Dubosiella abundance was significantly decreased.
- Muribaculaceae (a family of Bacteroidetes) was identified as a key class of bacteria affecting the intervention effect.
- Key Serum Metabolites: Multi-omics analysis identified two key serum metabolites linked to both microbial changes and behavioral outcomes:
- Hypoxanthine (C00262): This metabolite, involved in purine metabolism, is co-metabolized by both the host and gut microbes. It was significantly positively correlated with open-arm activity time and sociability, suggesting it plays a key role in regulating anxiety and social behavior.
- N-acetylneuraminic acid (C19910): This natural sugar acid is produced only by intestinal microbes and acts as a direct marker of microbial community activity. It was significantly negatively correlated with open-arm activity time and social ability.
In conclusion, the findings support the use of L. johnsonii YH1136 as a psychobiotic, revealing that its therapeutic effects are mediated through specific microbial shifts and the subsequent alteration of critical metabolites linked to neural function and SCZ symptoms. This research provides a crucial foundation for developing targeted
Source: Zheng, L., Xin, J., Ye, H., Sun, N., Gan, B., Gong, X., Bao, S., Xiang, M., Wang, H., Ni, X., Li, H., & Zhang, T. (2025). Lactobacillus Johnsonii YH1136 alleviates schizophrenia-like behavior in mice: a gut-microbiota-brain axis hypothesis study. BMC Microbiology, 25(191). https://doi.org/10.1186/s12866-025-03893-w.
