Gut microbial diversity and composition are significantly different among patients with bipolar disorder who have , those without, and healthy controls.
Specific bacteria related to glucose metabolism, such as Prevotella, Faecalibacterium, and Roseburia, are associated with cognitive impairment test scores.
Bacteria linked to inflammation, including Lachnoclostridium and Bacteroides, correlate with the severity of depressive symptoms.
led to depression-like behavior and impaired memory in mice that received microbiota from patients with cognitive impairment.
Mice with cognitive impairment displayed greater reductions in dendritic complexity and synaptic plasticity compared to those without impairment.
Supplementation of gut microbiota from healthy individuals partially reversed cognitive and emotional deficits in mice with cognitive impairment.
Simplified
BACKGROUND: is an intractable clinical manifestation of bipolar disorder (BD), but its underlying mechanisms remain largely unexplored. Preliminary evidence suggests that gut microbiota can potentially influence cognitive function by modulating synaptic plasticity. Herein, we characterized the gut microbial structure in BD patients with and without cognitive impairment and explored its influence on neuroplasticity in mice.
METHODS: The gut structure of microbiota in BD without cognitive impairment (BD-nCI) patients, BD with cognitive impairment (BD-CI) patients, and healthy controls (HCs) were characterized, and the correlation between specific bacterial genera and clinical parameters was determined. ABX-treated C57 BL/J male mice were transplanted with fecal microbiota from BD-nCI, BD-CI patients or HCs and subjected to behavioral testing. The change of gut microbiota in recipient mice and its influence on the dendritic complexity and synaptic plasticity of prefrontal neurons were examined. Finally, microbiota supplementation from healthy individuals in the BD-CI mice was performed to further determine the role of gut microbiota.
RESULTS: 16S-ribosomal RNA gene sequencing reveals that gut microbial diversity and composition are significantly different among BD-nCI patients, BD-CI patients, and HCs. The Spearman correlation analysis suggested that glucose metabolism-related bacteria, such as Prevotella, Faecalibacterium, and Roseburia, were correlated with cognitive impairment test scores, and inflammation-related bacteria, such as Lachnoclostridium and Bacteroides, were correlated with depressive severity. resulted in depression-like behavior, impaired working memory and object recognition memory in BD-CI recipient mice. Compared with BD-nCI mice, BD-CI mice exhibited more severely impaired object recognition memory, along with greater reductions in dendritic complexity and synaptic plasticity. Supplementation of gut microbiota from healthy individuals partially reversed emotional and cognitive phenotypes and neuronal plasticity in BD-CI mice.
CONCLUSIONS: This study first characterized the gut microbiota in BD-CI patients and highlighted the potential role of gut microbiota in BD-related cognitive deficits by modulating neuronal plasticity in mice model.
Key numbers
14 of 14 BD-CI patients
Participant Count
Total number of BD-CI patients analyzed in the study.
Lower than BD-nCI group
Microbial Diversity Decrease
Gut microbial diversity in BD-CI patients compared to BD-nCI patients.
BD-CI mice showed reductions in dendritic complexity
Dendritic Complexity Decrease
Comparison of dendritic complexity between BD-CI and control mice.
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Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the First Affiliated Hospital, School of Medicine of Zhejiang University (reference number #2017–397). All participants provided written informed consent. All animal experiments were approved by the Animal Experimental Ethical Inspection of the First Affiliated Hospital, Zhejiang University School of Medicine (Reference number 2024–376). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
