NeuroGI: a new way to explore the gut–brain axis

© Wyss Geneva / Dinis Sottomayor

Despite decades of research, the enteric nervous system and its role in gut physiology remains difficult to fully understand due to its complexity. By combining in vivo functional recordings with organ-scale 3D imaging, technologies developed by the NeuroGI team at the Wyss Center for Bio and Neuroengineering, based at the Campus Biotech in Geneva, offer a new, integrated way to explore the gut–brain axis.

These advances are detailed in two recent publications, which outline the underlying experimental approaches and their applications¹.

An open scientific challenge

Often referred to as the “second brain”, the enteric nervous system (ENS) plays a central role in regulating digestive functions, as well as in a wide range of disorders. Yet its study remains fragmented and restricted to indirect and imprecise measures of gut activity.

Structural imaging offers a detailed view of tissues, however a lack of tools to measure physiological activity does not enable the linking of morphological observations to the organ’s function. On the other hand, existing methods to observe electrical activity of the digestive tract are invasive and too localized. Between these two elements – namely cellular-scale morphology and organ-scale physiology – a gap persists.

Capturing gut activity in vivo

To address this challenge, the NeuroGI team developed a miniaturised endoscope capable of recording high-resolution electrical activity directly from the colon of live mice, without requiring a surgical procedure.

Equipped with 128 sensors, the device allows researchers to observe how smooth muscle action potentials organise into complex spatiotemporal patterns along the gastrointestinal tract. It also enables analysis of how these patterns change in response to pharmacological agents that modulate enteric neurotransmission.

This approach captures physiological activity in vivo and directly links experimental interventions to system-level responses.

Visualising the enteric nervous system at scale

Complementing this approach, the enGLOW method enables 3D visualisation of the enteric nervous system in cleared human and mouse gut tissues, across volumes of up to multiple cubic centimeters.

By combining tissue clearing, labelling and computational segmentation, this approach provides quantitative analysis of large tissue segments while preserving high resolution. It allows researchers to map neuronal networks and compare different models, both healthy and diseased.

By making ENS morphology measurable at this scale, enGLOW addresses a key gap between microscopic imaging and whole-organ analysis.

Linking structure and function

Taken separately, these tools address well-identified limitations. Together, they change the way the gut–brain axis can be studied.

The endoscope provides access to in vivo functional dynamics, while enGLOW offers a structural view at scale. Their complementarity paves the way for an integrated approach that links tissue organisation with electrical activity — a key step towards better understanding the mechanisms underlying gastrointestinal and neurodegenerative disorders.

Two questions for Michalina Gora, NeuroGI Group Leader

What has been the main limitation, until now, in linking structure and function in the enteric nervous system?

Electrophysiology has been instrumental in advancing our understanding of brain and heart function and is now a standard of care in clinical diagnosis. However, comparable tools have not been successfully translated to the digestive system due to a combination of technical and physiological challenges. Achieving minimally invasive, longitudinal functional measurements required the integration of neurotechnology with gastroenterology, neuroscience, microengineering and neurobiology. Incorporating morphological context further necessitated the adoption of advanced photonics tools. By bringing together these complementary areas of expertise within a single team—supported by the Wyss Center and an ERC Starting Grant—we have developed a quantitative and direct approach to measuring gut function and morphology within the context of the whole body.

 

What does this combined approach change in practice for understanding or studying gastrointestinal disorders?

Until now, gut–brain axis research has lacked minimally invasive methods capable of capturing functional activity with both high spatial resolution and broad coverage. Our mini-endoscopic platform addresses this gap by enabling longitudinal measurements of physiological function during disease progression. Its minimally invasive design makes it suitable for repeated measurements over time. We are particularly excited to collaborate with leading research partners developing treatments for neurodegenerative diseases such as Alzheimer’s and Parkinson’s, where a holistic, gut–brain perspective is increasingly recognized as essential.

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 853378).

¹Sobolewski, A., Planchette, A., Wójcicki, K. et al. Miniature endoscope for high resolution electrophysiological recordings from the colon of live mice. Nat Commun 17, 2363 (2026). https://doi.org/10.1038/s41467-026-69144-2
Planchette, A., Gantar, I., Scholler, J. et al. enGLOW 3D microscopy of the enteric nervous system in cleared human and mouse gut. Commun Biol 9, 357 (2026). https://doi.org/10.1038/s42003-026-09643-6