Ligilactobacillus murinus alleviates binge-eating behavior by restoring serotonin metabolism

Area of Science:

• Neuroscience
• Microbiology
• Gastroenterology
• Behavioral Science

Background:

• Overeating disorder (OD) involves binge eating without compensatory behaviors, linked to gut dysbiosis and altered serotonin (5-HT) metabolism.
• The precise microbial mechanisms influencing neurochemical changes in OD remain unclear.
• Existing research lacks a comprehensive understanding of the gut microbiota's role in OD pathogenesis.

Purpose of the Study:

• To investigate the role of gut microbiota in the neurochemical and behavioral aspects of overeating disorder (OD).
• To identify specific microbial species and mechanisms involved in serotonin (5-HT) dysregulation in OD.
• To evaluate the therapeutic potential of Ligilactobacillus murinus (L. murinus) as a probiotic intervention for OD.

Main Methods:

• Established a stress and food restriction mouse model exhibiting OD phenotypes and suppressed serotonin (5-HT) levels.
• Utilized antibiotic treatment to deplete gut microbiota and assessed its impact on binge-eating behavior and 5-HT metabolism.
• Employed 16S rRNA gene sequencing to characterize gut dysbiosis and performed targeted probiotic intervention with L. murinus.
• Investigated the role of serotonin (5-HT) synthesis and L. murinus-derived indole-3-acetic acid (IAA) in mediating therapeutic effects.

Main Results:

• Gut microbiota depletion exacerbated binge-eating behaviors and suppressed the serotonin (5-HT) pathway.
• OD was associated with gut dysbiosis, specifically a reduction in Ligilactobacillus abundance, which correlated positively with serum 5-HT.
• L. murinus probiotic intervention restored 5-HT metabolism and significantly ameliorated palatable food preference, energy intake, and food impulsivity.
• The benefits of L. murinus were dependent on 5-HT synthesis and mediated by IAA-induced activation of the aryl hydrocarbon receptor (AHR) signaling pathway.

Conclusions:

• Gut microbiota plays a critical role in modulating host serotonin (5-HT) metabolism and binge-eating behavior in overeating disorder (OD).
• Ligilactobacillus murinus (L. murinus) demonstrates significant therapeutic potential for OD by restoring 5-HT levels and improving related behaviors.
• The findings highlight L. murinus as a promising next-generation probiotic targeting the gut-brain axis for OD treatment via the IAA-AHR-5-HT pathway.