The intestine is not only a primary site of digestion and absorption, but also a critical interface where the intestinal immune and nervous systems interact. How it integrates food-derived, microbial, and mechanical stimuli in real time to generate dynamic physiological responses is a central question in the life sciences. However, in the highly complex intestinal microenvironment, precise and dynamic tracking of neurotransmitters has long remained a major technical challenge.
Recently, a study published in Science Bulletin reported a stretchable electrochemical sensing platform with high deformation insensitivity and strong antibiofouling capability. The platform enables in situ capture of dynamic small-molecule chemical signals in the gut, and it revealed a new mechanism underlying enhanced intestinal mechanosensation under microbe-related stimulation. Notably, the platform combines a one-dimensional nanoconductive network with a host-guest-functionalized shell, establishing a foundational electrochemical sensing framework capable of simultaneously minimizing mechanical artifacts, macromolecular biofouling, and cross-interference from small molecules. Monitoring within the intestinal lumen provides a highly challenging yet ideal validation scenario, while the design strategy for handling mechanical perturbation, biofouling, and molecular interference also shows promise for use in other complex in vivo environments.
Studies have shown that enterochromaffin cells (ECs) play important roles in intestinal sensory and motor regulation. These specialized intestinal epithelial cells release 5-hydroxytryptamine (5-HT, serotonin) and are central to luminal signal adaptation and motility pattern switching. Dysregulation of the 5-HT system is closely associated with functional disorders such as irritable bowel syndrome (IBS) and chronic constipation. However, conventional flexible sensing devices often suffer severe signal distortion or device failure when faced with three major challenges: strong rhythmic intestinal peristalsis, complex biofouling that readily passivates electrodes, and cross-interference from structurally similar small molecules. Achieving real-time, accurate monitoring of 5-HT under these three constraints has therefore become a major bottleneck in sensor development.
To address this problem, the team adopted a materials science-electrochemistry strategy and built flexible electrodes based on polydimethylsiloxane (PDMS). An unordered gold nanotube (Au NT) conductive network was introduced onto the electrode surface. Relative sliding among the nanotubes maintained continuity of the conductive pathways during deformation, allowing stable output under stretching, bending, and even expansion. This significantly reduced mechanical artifacts and enabled adaptation to the dynamic mechanical environment of the gut. This nanostructural design reduced the risk of deformation-induced disruption of conductive pathways and improved output continuity and stability.
On this basis, the team further designed a poly(3,4-ethylenedioxythiophene) (PEDOT) functional coating doped with 2-hydroxypropyl-β-cyclodextrin (HC). This "smart interface" provides both molecular recognition and anti-biofouling functions. First, host-guest interactions within the hydrophobic cavity of cyclodextrin enable highly selective capture of 5-HT, allowing effective discrimination even in the presence of structurally similar molecules such as dopamine and epinephrine. Second, the hydrophilic outer layer of HC suppresses protein adsorption and the deposition of 5-HT oxidation products, enabling stable antibiofouling performance for up to 72 hours in complex biological fluids and cell culture systems.
Performance tests showed that the sensor achieved a sensitivity of 4.85 μA/(μM cm 2 ) for 5-HT, a detection limit as low as 3.9 nM, and a linear range of 10 to 20 μM. These metrics indicate strong capability for capturing trace target molecules and meet monitoring requirements across pathophysiological concentration ranges at both the cellular and tissue levels.
Using this platform, the researchers further analyzed the mechanism of gut immune-mechanical signal integration. By establishing an integrated cell and ex vivo tissue culture-detection system, they achieved in situ 5-HT monitoring at both the cellular and tissue levels under near-physiological conditions. The results showed that stimuli mimicking viral (poly(I:C)), bacterial (LPS), and fungal (zymosan) infection all significantly enhanced the mechanical sensitivity of ECs and markedly increased 5-HT release.
Further mechanistic studies showed that these microbe-related stimuli activate pattern-recognition receptors on ECs and exert dual regulatory effects through the p38 MAPK pathway: upregulating the mechanosensitive ion channel Piezo2 to enhance mechanically induced secretion, and upregulating tryptophan hydroxylase 1 (TPH1) to increase intracellular 5-HT reserves. At the tissue level, microbe-related stimulation also increased EC density. These findings indicate that ECs are not merely effector cells, but also function as in vivo "sensors" that integrate multidimensional chemical, mechanical, and immune signals within the intestinal lumen.
Under pathological stimulation, ECs can reset their response threshold through dual regulation—enhancing neurotransmitter synthesis and storage while increasing sensitivity to mechanical stimulation—and then act as intestinal "signal amplifiers" in the immune-mechanical-inflammatory process. This discovery provides new insight into how the gut may maintain a mechanically hypersensitive state during and after infection, and how excessive 5-HT release can drive abnormal motility responses, thereby helping explain the emergence of IBS-like symptom phenotypes.
Science Bulletin
Experimental study