Periodic Reporting for period 1 - EnterBio (Enteric Bioelectronics for Sensing and Stimulating the CNS)
Reporting period: 2024-03-01 to 2025-02-28
The human brain and gut are connected in profound and intricate ways. The gut’s intrinsic neural system, known as the enteric nervous system (ENS), is sometimes referred to as the “second brain”. Recent research has shown that this system doesn’t just passively respond to brain signals—it can actively influence brain function and may play a role in neurological disorders like epilepsy, Alzheimer’s disease, and Parkinson’s disease. Yet, this critical connection between gut and brain remains underexplored, and no tools currently exist to measure or modulate brain function through the ENS.
EnterBio is an ambitious EU-funded research project that aims to pioneer this new scientific and technological frontier. It brings together expertise in bioelectronics, neuroscience, and physiology to develop a novel platform that enables sensing and stimulation of the ENS, using bioelectronic devices originally designed for the central nervous system (CNS). The long-term vision is to provide non-invasive alternatives to brain implants by targeting the gut as an accessible and robust interface to the nervous system.
The project’s four core objectives are to:
1. Develop flexible, implantable devices for chemical and electrical sensing/stimulation of the ENS.
2. Elucidate how ENS signals influence brain activity and cognition.
3. Demonstrate proof-of-concept therapies for CNS disorders using gut-based interventions.
4. Establish a new research and innovation platform for studying gut-brain interactions.
If successful, EnterBio could transform the way we understand and treat neurological diseases—unlocking gut-based strategies for brain modulation that are more accessible, less invasive, and potentially more effective than current technologies.
EnterBio is an ambitious EU-funded research project that aims to pioneer this new scientific and technological frontier. It brings together expertise in bioelectronics, neuroscience, and physiology to develop a novel platform that enables sensing and stimulation of the ENS, using bioelectronic devices originally designed for the central nervous system (CNS). The long-term vision is to provide non-invasive alternatives to brain implants by targeting the gut as an accessible and robust interface to the nervous system.
The project’s four core objectives are to:
1. Develop flexible, implantable devices for chemical and electrical sensing/stimulation of the ENS.
2. Elucidate how ENS signals influence brain activity and cognition.
3. Demonstrate proof-of-concept therapies for CNS disorders using gut-based interventions.
4. Establish a new research and innovation platform for studying gut-brain interactions.
If successful, EnterBio could transform the way we understand and treat neurological diseases—unlocking gut-based strategies for brain modulation that are more accessible, less invasive, and potentially more effective than current technologies.
During the first year of EnterBio, the consortium focused on developing and validating the key technologies needed to stimulate and record signals from the ENS. The work was centered around bioelectronic device design, fabrication, and initial testing both in vitro (cell culture) and in vivo (animal models).
Major achievements include:
• Electrical stimulation tools: Thin-film organic electrode arrays were developed for implantation in the colon. These devices successfully activated targeted neural populations in the spinal cord when implanted in mice, meeting the project’s first major milestone.
• Chemical delivery tools: Iontronic devices, capable of highly localized and fluid-free delivery of neurotransmitters, were validated in neural tissue models. These tools are being adapted for future gut-implanted applications.
• Graphene-based sensors: FORTH established protocols for fabricating flexible, laser-patterned graphene electrodes, offering a promising route toward miniaturized, high-performance sensing components.
• Validation platforms: AMU developed a wireless telemetry system for chronic monitoring of brain and gut activity in freely moving rats. Early experiments demonstrated that specific neurons in the brain are modulated by gastric rhythms—an important first step in proving gut-to-brain signal transmission.
In total, EnterBio completed multiple deliverables and reached its first scientific milestone (MS1). Several prototypes have been fabricated, validated, and integrated into experimental platforms. This foundational work paves the way for ENS-to-CNS modulation studies planned in the second reporting period.
Major achievements include:
• Electrical stimulation tools: Thin-film organic electrode arrays were developed for implantation in the colon. These devices successfully activated targeted neural populations in the spinal cord when implanted in mice, meeting the project’s first major milestone.
• Chemical delivery tools: Iontronic devices, capable of highly localized and fluid-free delivery of neurotransmitters, were validated in neural tissue models. These tools are being adapted for future gut-implanted applications.
• Graphene-based sensors: FORTH established protocols for fabricating flexible, laser-patterned graphene electrodes, offering a promising route toward miniaturized, high-performance sensing components.
• Validation platforms: AMU developed a wireless telemetry system for chronic monitoring of brain and gut activity in freely moving rats. Early experiments demonstrated that specific neurons in the brain are modulated by gastric rhythms—an important first step in proving gut-to-brain signal transmission.
In total, EnterBio completed multiple deliverables and reached its first scientific milestone (MS1). Several prototypes have been fabricated, validated, and integrated into experimental platforms. This foundational work paves the way for ENS-to-CNS modulation studies planned in the second reporting period.
EnterBio is breaking new ground in both neuroscience and bioelectronics by shifting the focus of neuromodulation technologies away from the brain and toward the gut. This disruptive concept—neuromodulation via the ENS—offers numerous advantages over traditional brain implants: lower surgical risk, greater accessibility, and better compatibility with the body’s natural physiology.
The project has already delivered several technical breakthroughs, including:
• The first in vivo demonstration of colonic bioelectronic stimulation activating spinal neurons.
• Novel iontronic drug delivery systems tailored for the gut environment.
• Fabrication of the first laser-patterned graphene electrode arrays for enteric applications.
• Multimodal gut-brain telemetry in animal models, a key enabler for future closed-loop therapies.
Looking ahead, EnterBio is on track to demonstrate full chemical and electrical modulation of the gut-brain axis using integrated devices. Potential impacts include:
• Improved therapies for epilepsy and other neurological disorders through minimally invasive gut implants.
• Deeper scientific understanding of how the gut influences cognition, emotion, and disease.
• New product classes in the neurotechnology and medtech markets, including gut-based implants and smart diagnostic tools.
To ensure uptake and long-term success, the project has implemented strong Open Science practices and is actively engaging with clinicians, industry, and the public. A clear exploitation plan is in place, with IPR management and technology transfer led by commercialization specialists. As the field of gut-brain interfaces grows, EnterBio is poised to remain at its forefront—scientifically, clinically, and commercially.
The project has already delivered several technical breakthroughs, including:
• The first in vivo demonstration of colonic bioelectronic stimulation activating spinal neurons.
• Novel iontronic drug delivery systems tailored for the gut environment.
• Fabrication of the first laser-patterned graphene electrode arrays for enteric applications.
• Multimodal gut-brain telemetry in animal models, a key enabler for future closed-loop therapies.
Looking ahead, EnterBio is on track to demonstrate full chemical and electrical modulation of the gut-brain axis using integrated devices. Potential impacts include:
• Improved therapies for epilepsy and other neurological disorders through minimally invasive gut implants.
• Deeper scientific understanding of how the gut influences cognition, emotion, and disease.
• New product classes in the neurotechnology and medtech markets, including gut-based implants and smart diagnostic tools.
To ensure uptake and long-term success, the project has implemented strong Open Science practices and is actively engaging with clinicians, industry, and the public. A clear exploitation plan is in place, with IPR management and technology transfer led by commercialization specialists. As the field of gut-brain interfaces grows, EnterBio is poised to remain at its forefront—scientifically, clinically, and commercially.