Heat-killed Lactobacillus brevis SBC8803 reduces anxiety-like behavior in zebrafish via gut-brain axis modulation
Background
Anxiety disorders are a global mental health challenge, often managed with pharmacological interventions that can have significant side effects. The microbiota-gut-brain axis has emerged as a critical modulator of mental health, with psychobiotics—live or inactivated microorganisms—showing promise. Lactobacillus brevis SBC8803 (SBC8803), a heat-killed paraprobiotic, has previously demonstrated the ability to enhance serotonin (5-HT) signaling and alleviate stress in mammals. However, the precise gut-brain pathways mediating these anxiolytic effects remain underexplored, particularly at a systems level.
Study Design
Adult male AB-strain zebrafish were fed a diet containing heat-killed SBC8803 for 4 weeks. Anxiety-like behavior was assessed using the novel tank test, measuring latency to enter and frequency of entries into the upper half of the tank. To elucidate mechanisms, brain RNA sequencing was performed to identify differentially expressed genes, alongside V3-V4 region 16S rRNA amplicon sequencing of intestinal contents. Integrative multi-omics analyses, including Gene Set Variation Analysis (GSVA) combined with DIABLO-based data integration and residual correlation analysis, were used to link microbial changes to brain signaling pathways.
Results
SBC8803-treated fish consistently exhibited reduced anxiety-like behavior. They showed a shorter latency to enter the upper half of the tank and made more frequent entries into this region, indicating decreased avoidance. Brain transcriptomic profiling revealed differentially expressed genes and significant enrichment of pathways related to serotonin receptor signaling, CREB (cAMP-response element-binding protein), and oxytocin signaling, suggesting enhanced monoaminergic and plasticity-related neural activity. Microbiome functional prediction indicated SBC8803-associated shifts in lipid and vitamin metabolism, specifically highlighting pathways related to riboflavin (vitamin B2) and tryptophan.
GSVAcombined withDIABLO-based data integrationrevealed coordinated changes between microbial metabolic pathways and brain signaling pathways, consistent with avitamin B-serotonin-anti-inflammatory axislinking gut metabolism to neural regulation.
Key Findings
- Oral Lactobacillus brevis SBC8803 reduced anxiety-like behavior in zebrafish.
- Treated fish showed shorter latency and more frequent entries into the upper tank.
- Brain transcriptomics revealed enriched
serotonin receptor,CREB, andoxytocinsignaling pathways. - Gut microbiome shifts included altered lipid and vitamin metabolism, particularly
riboflavinandtryptophanpathways. - Integrated analysis identified a
vitamin B-serotonin-anti-inflammatory axislinking gut and brain.
Why It Matters
This study highlights the potential of paraprobiotics like SBC8803 as a novel, non-pharmacological strategy for anxiety management, offering a potentially safer alternative or adjunct to traditional CNS-targeted drugs. The identification of a vitamin B-serotonin-anti-inflammatory axis provides a mechanistic framework, suggesting that specific dietary interventions could modulate gut metabolism to influence brain function. Future protocols for anxiety support could incorporate specific heat-killed bacterial strains, potentially leveraging their impact on vitamin and tryptophan metabolism to enhance endogenous serotonin and oxytocin pathways, moving towards more holistic mental health interventions.
lactobacillus-brevis-sbc8803
anxiety
gut-brain-axis
paraprobiotic
zebrafish
serotonin