Exploratory study of gut-brain axis in humans using transcutaneous auricular vagus nerve stimulation
Presented During: Poster Session 3
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Presented During: Poster Session 4
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Poster No:
1925
Submission Type:
Abstract Submission
Authors:
Sakura Nishijima1,3, Kazumasa Uehara2,3, Naoki Takahashi3, Shohei Tsuchimoto3, Yuka Okazaki1,3, Masaaki Hirayama4, Kinji Ohno5, Keiichi Kitajo1,3
Institutions:
1The Graduate University for Advanced Studies (SOKENDAI), Aichi, Japan, 2Toyohashi University of Technology, Aichi, Japan, 3National Institute for Physiological Sciences, Aichi, Japan, 4Chubu University, Aichi, Japan, 5Nagoya University, Aichi, Japan
First Author:
Co-Author(s):
Introduction:
Brain-gut communication is a complex bidirectional interaction between the gastrointestinal tract and the central nervous system. It involves endocrine, immune, and neural mechanisms, including vagus nerve signaling. The vagus nerve, linking the brain and gut through its afferent and efferent branches, serves as a critical route in the bidirectional communication of this axis. Previous studies have suggested that, the vagus afferent fibers can sense and relay gut microbiota signals to the brain, potentially causing brain disorders including depression (Breit et al., 2018 Front Psychiatry). Additionally, human studies have observed a correlation between brain and gastric activity using BOLD signals and electrogastrography (EGG) / electrointestinography (EIG) signals. These studies reveal connections between the gut and specific brain regions (Richer et al., 2017 Neuroimage; Hashimoto et al., 2015 Neuroscience).
However, much remains to be understood about the electrophysiological aspects of brain-gut connectivity and the relationships among the brain, gut, and vagus nerve.
In this exploratory study, we investigated the effects of vagal stimulation with taVNS on the electrophysiological coupling between the brain and gut. This study aimed to reveal the role of the vagus nerve in brain-gut interactions.
However, much remains to be understood about the electrophysiological aspects of brain-gut connectivity and the relationships among the brain, gut, and vagus nerve.
In this exploratory study, we investigated the effects of vagal stimulation with taVNS on the electrophysiological coupling between the brain and gut. This study aimed to reveal the role of the vagus nerve in brain-gut interactions.
Methods:
We developed a method to measure gastrointestinal electrical activity with EIG using bipolar 8-ch recordings, we simultaneously recorded EEG (64 ch), electrocardiograms (ECG), respiratory signals, and electrooculograms (EOG) (Fig1). In a double-blind crossover design, participants attended two experimental sessions on separate days, with measurements conducted at a fixed time to control for circadian variations in gastrointestinal activity. At each session, electrophysiological activities in the resting state were measured before, during, and after 15 minutes of taVNS with eleven participants. Real stimulation was applied to the tragus, and sham stimulation to the earlobe. After the experiment, the gut microbiota was collected from the participants' feces and analyzed using 16S rRNA sequencing.
Results:
Analysis of resting-state recordings revealed prominent phase-amplitude coupling (PAC) (Tort et al., 2010 Journal of Neurophysiology) between the low-frequency EIG phase and alpha-band EEG amplitude, which we hypothesized to reflect brain-gut communication. Additionally, taVNS appeared to modulate the gut-brain PAC. The highest coupling was observed during rest before stimulation (Fig1). The PAC values correlated with indicators of parasympathetic activity calculated from ECG. Furthermore, the EEG-EIG PAC values after real stimulation showed a correlation with the alpha diversity scores of the gut microbiota.
·Participant and electrode pair-averaged EIG-EEG PAC values in a pre-stimulation resting condition
Conclusions:
Our preliminary results on brain-gut interaction indicate the existence of electrophysiological coupling in brain-gut interaction and the potential for modulation by taVNS. The correlation between PAC after real stimulation and the gut microbiota suggests an interrelationship among the vagus nerve, brain, and gut microbiota. On the other hand, it is still unclear whether this correlation is direct or indirect. Therefore, to understand the detailed mechanisms, detailed analyses such as investigating the relationship with the composition of the gut microbiota and partial correlation analysis are necessary.
In our ongoing analyses, we plan to conduct integrative analyses using EEG, EIG, autonomic nervous system indicators, and gut microbiota data. Additionally, we plan to increase the number of participants and investigate the strength of the gut-brain connection at different electrode positions in the gut, as well as transfer entropy analysis.
These preliminary findings provide initial evidence for the integrated connection between the brain and gut althrough the vagus nerve and the gut microbiota, though further validation with a larger sample size is needed.
In our ongoing analyses, we plan to conduct integrative analyses using EEG, EIG, autonomic nervous system indicators, and gut microbiota data. Additionally, we plan to increase the number of participants and investigate the strength of the gut-brain connection at different electrode positions in the gut, as well as transfer entropy analysis.
These preliminary findings provide initial evidence for the integrated connection between the brain and gut althrough the vagus nerve and the gut microbiota, though further validation with a larger sample size is needed.
Brain Stimulation:
Non-Invasive Stimulation Methods Other 2
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Novel Imaging Acquisition Methods:
EEG 1
Keywords:
Data analysis
Electroencephaolography (EEG)
Other - Gut-brain axis
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
Hashimoto, T., et al. (2015). Neural Correlates of Electrointestinography: Insular Activity Modulated by Signals Recorded from the Abdominal Surface. Neuroscience, 289, 1-8.
Richter, C. G., et al. (2017). Phase-Amplitude Coupling at the Organism Level: The Amplitude of Spontaneous Alpha Rhythm Fluctuations Varies with the Phase of the Infra-Slow Gastric Basal Rhythm. Neuroimage, 146, 951-958.
Combrisson, E., et al. (2020). Tensorpac: An Open-Source Python Toolbox for Tensor-Based Phase-Amplitude Coupling Measurement in Electrophysiological Brain Signals. PLoS Computational Biology, 16(10).
Tort, A. B. L., et al. (2010). Measuring Phase-Amplitude Coupling Between Neuronal Oscillations of Different Frequencies. Journal of Neurophysiology, 104(2), 1195-210.