Gut in Tube─Continuous Measurement of Metabolic Crosstalk between Cell Populations in Heterogeneous Samples by NMR Imaging

In complex living systems, such as the human gut, the interplay between the multiple cell types present is governed by the exchange of small molecule metabolites. However, at present, we lack techniques capable of monitoring this crosstalk in real time and with spatial resolution. Here, we present a model of the human gut in a 5 mm NMR tube that accounts for the intraluminal, mucosal, and colonocyte spaces. Cells are cultured in different spatial regions enabling metabolites, changes in pH, and the effects of exogenous molecules to be monitored exclusively using localized NMR techniques. Our model represents a high-throughput, readily available, and widely applicable approach to the study of living systems with multiple cell types on a molecular level. We used our model to explore the interplay between gut bacteria and colonocytes in the human large intestine and study the molecular concentration gradients naturally present in these systems. Such studies could help shed light on the crucial role played by the gut microbiota in maintaining gut homeostasis, modulating immune responses, metabolizing nutrients, and regulating host physiology.