Functional optical imaging has made remarkable strides in neuroscience. Techniques such as calcium imaging have illuminated the dynamics of live brain activity, while optogenetics enables the precise control of neural circuits in freely moving animals. Functional near-infrared spectroscopy (fNIRS) allows noninvasive monitoring of neural activity in humans. Gaps remain, however, in our understanding of the brain’s link to other networks in the body, such as the digestive system. The enteric nervous system (ENS) is central to gut-brain communication and governs gut functions, including nutrient absorption, immune monitoring, and hormone regulation. Disorders of gut-brain interaction affect nearly 40% of the global population, according to the Rome Foundation. Gut health is fundamental to one’s daily well-being and is increasingly linked to systemic diseases, including neurodegeneration and mental health disorders. Technologies such as multiphoton microscopy have begun to reveal the complex interplay between enteric neurons and the surrounding cells in ex vivo studies. Endoscopic optical coherence tomography has been useful for the investigation of digestive cancers but requires design changes to capture enteric network morphology and function. Photoacoustic imaging could provide insights into vascular responses and neural activity in the gut wall by combining optical excitation with ultrasound detection. Label-free spectroscopic techniques could provide molecular fingerprinting of neurotransmitters. And hyperspectral imaging could be used for mapping tissue oxygenation and metabolic states, revealing the chemical signatures of gut-brain signaling without exogenous markers. The human gut, with enteric neurons deeply embedded in its wall, offers an ideal model for advancing methods to extract optical signals from turbid media. Adapting exogenous contrast agents could greatly enhance visualization of the ENS. Combined with multimodal imaging platforms that integrate fluorescence with structural and metabolic readouts, this approach could help differentiate diseases with overlapping symptoms but distinct origins. Applying technologies to the brain presents higher risks, whereas exploring the gut is less risky for patients. This makes the gut a more approachable location for first-in-human experiments and rapid technological deployment. Optical technologies must be tailored to study neuron-related gut functions in vivo. Optimizing optical technologies for the unique demands of gut-brain research requires a deep understanding of organ physiology and a multidisciplinary approach spanning biology, neuroscience, engineering, and data science. This approach will not only illuminate the ENS but also shed light on broader health issues — from chronic digestive disorders to mental health — ultimately improving patient outcomes across multiple medical specialties. Meet the author Michalina Gora-Gioux, Ph.D., is a group leader at the Wyss Center. She is affiliated with the ICube Laboratory in Strasbourg, France, and the French National Centre for Scientific Research (CNRS). She obtained her Ph.D. in physics and biomedical engineering from Nicolaus Copernicus University in Poland; email: michalina.gora@wysscenter.ch. The views expressed in ‘BioOpinion’ are solely those of the author and do not necessarily represent those of Photonics Media. To submit a BioOpinion, send a few sentences outlining the proposed topic to doug.farmer@photonics.com. Accepted submissions will be reviewed and edited for clarity, accuracy, length, and conformity to Photonics Media style.