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Updated: Jan 14, 2026

Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation
Published on: December 29, 2023
From gut to glymphatic system: Causal pathways converge in midbrain glutamatergic neurons
1School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Background:
The glymphatic system plays a crucial role in brain waste clearance, with dysfunction linked to various neurological disorders. While evidence suggests interactions between gut microbiota and brain health, the causal relationships between gut microbiota and glymphatic function remain poorly understood.
Objective:
We aimed to investigate the bidirectional causal relationships between gut microbiota composition and glymphatic system function, and to identify the neuroanatomical and cellular substrates of these associations. Glymphatic activity was quantified by the Diffusion Tensor Image Analysis Along the Perivascular Space (ALPS) index.
Methods:
We performed two-sample bidirectional Mendelian randomization analyses using genome-wide association study summary statistics from European ancestry cohorts (gut microbiota: n = 18,340; ALPS index: n = 31,021). Linkage disequilibrium score regression was employed to assess shared genetic architecture. Spatial transcriptomic mapping using the gsMap framework with embryonic mouse brain tissue was conducted to localize genetic signals at anatomical and cellular levels.
Results:
We identified 21 significant causal relationships between gut microbiota and ALPS indices by bidirectional Mendelian randomization, with Veillonella and Barnesiella showing consistent negative associations with all three ALPS indices (left, mean, and right). Catenibacterium exhibited a complex bidirectional relationship with Right ALPS. Spatial transcriptomic mapping revealed convergent enrichment of microbiota and ALPS-associated genetic signals in the midbrain region, with predominant localization to glutamatergic neurons (>40 % enrichment). Linkage disequilibrium score regression (LDSC) analysis confirmed these relationships were independent of shared genetic architecture.
Conclusion:
Our findings establish causal relationships between specific gut microbiota and glymphatic function, with convergent neuroanatomical and cellular substrates in midbrain glutamatergic neurons.
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