Periodic Reporting for period 1 - DeepDive (Advanced ingestibles for probing the nexus between gastrointestinal functions and physical/mental well-being in animals and humans)
Periodo di rendicontazione: 2024-01-01 al 2025-06-30
The DeepDive project is grounded in the need for innovative tools to monitor and modulate gastrointestinal (GI) functions, increasingly recognized as crucial regulators of both physical and mental health. The gut-brain axis, a bidirectional communication system between the central nervous system and the GI tract, is implicated in a wide range of neuropsychiatric disorders (anxiety, depression, autism).
Despite this, current methods for studying GI physiology are invasive, costly, and often limited to a single parameter.
DeepDive aims to develop a groundbreaking class of ingestible devices capable of simultaneously recording multiple GI signals (pH, temperature, pressure) and, for the first time, stimulating enteric neurons. These capsules will be smaller, cheaper, and more versatile than existing technologies.
By integrating cutting-edge materials science, electronics, and neuroscience, DeepDive seeks to deliver proof-of-concept evidence of gut-brain causality and provide novel biomarkers of well-being and stress in humans and animals.
Despite this, current methods for studying GI physiology are invasive, costly, and often limited to a single parameter.
DeepDive aims to develop a groundbreaking class of ingestible devices capable of simultaneously recording multiple GI signals (pH, temperature, pressure) and, for the first time, stimulating enteric neurons. These capsules will be smaller, cheaper, and more versatile than existing technologies.
By integrating cutting-edge materials science, electronics, and neuroscience, DeepDive seeks to deliver proof-of-concept evidence of gut-brain causality and provide novel biomarkers of well-being and stress in humans and animals.
WP1 Exp1 To investigate novel physiological markers of gastrointestinal (GI) function, we collected data from 40 healthy volunteers, integrating deep gastric signals (pH, temperature, pressure) via ingestible SmartPills, superficial gastric signals via electrogastrography (EGG), and neural activity through EEG. Participants reported perceived hunger before and after a standardized meal. Resting-state stomach-brain coupling was recorded in both conditions. Our analyses focused on Phase-Amplitude Coupling (PAC) between EGG and EEG. Preliminary results indicate that postprandial PAC strength positively correlates with satiety, suggesting that enhanced stomach-brain coupling may serve as a physiological marker of fullness. EEG activity modulated by gastric phase was particularly evident in alpha frequencies over central regions. In addition, we explored the psychological relevance of GI markers using validated self-report measures. Significant correlations emerged between SmartPill-derived gastric parameters and personality traits: lower gastric pH was associated with higher disgust sensitivity, and higher gastric temperature with greater interoceptive awareness. Exp2 We investigated the physiological effects of acute stress on the GI system by integrating SmartPIlls, superficial (EGG) measurements, and on the cardiac system (ECG). A total of 36 healthy participants were exposed to a validated virtual reality-based stress induction protocol designed to elicit strong psychosocial stress responses. Participants reported their subjective stress and GI sensations.Results revealed that higher levels of perceived stress were associated with a less acidic gastric environment (higher pH), increased self-reported GI discomfort, elevated heart rate, and reduced heart rate variability, indicating autonomic imbalance driven by parasympathetic withdrawal.
WP2.DeepDive has achieved two key technical milestones: the design and simulation of a high-efficiency telemetry system for novel ingestible capsules, and the development of a novel sensing strategy for recording enteric neuronal activity.
We conducted a comprehensive review of commercial ingestible capsules, identifying limitations in wireless telemetry and localization accuracy. A new miniaturized capsule was designed featuring a loop antenna integrated into its external surface. Using numerical dosimetry and high-resolution anatomical models (Sim4Life), multiple capsule positions along the GI tract were simulated. Results confirmed compliance with SAR safety limits and efficient electromagnetic propagation at 2.45GHz. Subsequently, different RX configurations, single-ring, mini-arrays, and a full body-array, were tested to optimize signal reception and enable capsule localization. The body-array solution demonstrated high spatial resolution and robust telemetry across all GI segments. Extensive modeling of the enteric nervous system was carried out. The novel capsules were equipped with gold ring electrodes for electrophysiological sensing. A millimetric and a whole-intestine model were developed to simulate electrical signals generated by enteroendocrine neuropod cells. Realistic action potentials, including noise and latency, were reconstructed from biological data and applied to 3D models in COMSOL. Simulations showed that the capsule could detect signals in the range of 10–35 mV depending on its position and cell density, confirming the feasibility of in vivo sensing.
WP3 To assess the feasibility of capsule ingestion and investigate animal GI markers of stress, we established a scientific collaboration with Prof. G. Marruchella, expert in swine pathology at the University of Teramo. Initial activities involved testing the ingestion of both commercial SmartPill devices and a novel ingestible prototype (sensor-free, smaller form factor) specifically designed for animal comfort and translational potential. Trials were conducted in dedicated veterinary research facilities. Each piglet was administered either the SmartPill or the new prototype. We monitored the feasibility of ingestion, capsule transit, expulsion, and integrity of the external coating post-expulsion.
The results revealed that the SmartPill, due to its size and rigidity, caused discomfort and stress during ingestion in piglets. In contrast, the new prototype was well tolerated, easily ingested, and expelled without adverse effects. This confirmed the superiority of the novel capsule’s design in terms of animal compatibility and suggested high translational applicability in human use. WP4 An in depth analysis to align the new product to the current research and industry needs is ongoing along with an effective IPR strategy to protect the novel inglestibles with appropriate IP mechanisms. Results dissemination, both in terms of publications and datasets, is ongoing.
WP2.DeepDive has achieved two key technical milestones: the design and simulation of a high-efficiency telemetry system for novel ingestible capsules, and the development of a novel sensing strategy for recording enteric neuronal activity.
We conducted a comprehensive review of commercial ingestible capsules, identifying limitations in wireless telemetry and localization accuracy. A new miniaturized capsule was designed featuring a loop antenna integrated into its external surface. Using numerical dosimetry and high-resolution anatomical models (Sim4Life), multiple capsule positions along the GI tract were simulated. Results confirmed compliance with SAR safety limits and efficient electromagnetic propagation at 2.45GHz. Subsequently, different RX configurations, single-ring, mini-arrays, and a full body-array, were tested to optimize signal reception and enable capsule localization. The body-array solution demonstrated high spatial resolution and robust telemetry across all GI segments. Extensive modeling of the enteric nervous system was carried out. The novel capsules were equipped with gold ring electrodes for electrophysiological sensing. A millimetric and a whole-intestine model were developed to simulate electrical signals generated by enteroendocrine neuropod cells. Realistic action potentials, including noise and latency, were reconstructed from biological data and applied to 3D models in COMSOL. Simulations showed that the capsule could detect signals in the range of 10–35 mV depending on its position and cell density, confirming the feasibility of in vivo sensing.
WP3 To assess the feasibility of capsule ingestion and investigate animal GI markers of stress, we established a scientific collaboration with Prof. G. Marruchella, expert in swine pathology at the University of Teramo. Initial activities involved testing the ingestion of both commercial SmartPill devices and a novel ingestible prototype (sensor-free, smaller form factor) specifically designed for animal comfort and translational potential. Trials were conducted in dedicated veterinary research facilities. Each piglet was administered either the SmartPill or the new prototype. We monitored the feasibility of ingestion, capsule transit, expulsion, and integrity of the external coating post-expulsion.
The results revealed that the SmartPill, due to its size and rigidity, caused discomfort and stress during ingestion in piglets. In contrast, the new prototype was well tolerated, easily ingested, and expelled without adverse effects. This confirmed the superiority of the novel capsule’s design in terms of animal compatibility and suggested high translational applicability in human use. WP4 An in depth analysis to align the new product to the current research and industry needs is ongoing along with an effective IPR strategy to protect the novel inglestibles with appropriate IP mechanisms. Results dissemination, both in terms of publications and datasets, is ongoing.
By integrating ingestible capsules, electrogastrography, and EEG in humans, we identified novel brain-gut coupling patterns. Specifically, PAC between gastric and alpha-band cortical rhythms correlated with satiety levels, offering a promising physiological marker of satiety. Furthermore, SmartPill-derived gastric signals (pH, temperature) were significantly associated with psychological traits such as disgust sensitivity and interoceptive awareness, highlighting a potential physiological basis for individual differences in core affective dimensions and mental health risk factors.
Under stress, we demonstrated that acute psychosocial challenges modulate deep gastric signals, with elevated pH and cardiac-autonomic imbalances (increased HR, reduced HRV) indicating parasympathetic withdrawal. These findings highlight the crucial role GI activity in stress-related responses. Technologically, we designed and simulated a novel ingestible capsule capable of recording enteric neuronal signals and transmitting wirelessly with high spatial resolution. Advanced modeling confirmed its feasibility and compliance with safety standards. In piglets, the new capsule prototype showed superior biocompatibility and ease of ingestion compared to existing devices. Future uptake requires continued in vivo validation, refinement of signal acquisition, and steps toward regulatory approval and market access. This work lays the foundation for translational applications in both human and animal health, supporting next-generation diagnostics for gut-brain disorders.
Under stress, we demonstrated that acute psychosocial challenges modulate deep gastric signals, with elevated pH and cardiac-autonomic imbalances (increased HR, reduced HRV) indicating parasympathetic withdrawal. These findings highlight the crucial role GI activity in stress-related responses. Technologically, we designed and simulated a novel ingestible capsule capable of recording enteric neuronal signals and transmitting wirelessly with high spatial resolution. Advanced modeling confirmed its feasibility and compliance with safety standards. In piglets, the new capsule prototype showed superior biocompatibility and ease of ingestion compared to existing devices. Future uptake requires continued in vivo validation, refinement of signal acquisition, and steps toward regulatory approval and market access. This work lays the foundation for translational applications in both human and animal health, supporting next-generation diagnostics for gut-brain disorders.