Gut in tube – continuous measurement of metabolic crosstalk between gut microbiota and colonocytes by NMR imaging

Abstract

The human gut has emerged as a highly promising candidate for predicting the onset of pathologies and monitoring disease pro-gression. The gut microbiota plays a crucial role in maintaining gut homeostasis, modulating immune responses, metabolizing nutri-ents and regulating host physiology. These functions have been linked to the interplay between gut bacteria and colonocytes in the human large intestine. At present, we lack high-throughput techniques capable of monitoring the crosstalk between these species on a molecular level in real time. In this work, we develop a model of the human large intestine in a 5 mm NMR tube that accounts for the intraluminal, mucosal and colonocyte spaces. Through the use of chemical shift imaging techniques, we follow changes to the pH in real time across different parts of the simulated large intestine and monitor the crosstalk between colonocytes and gut bacteria mediated by short-chain fatty acids. Finally, we demonstrate the in vitro model’s utility in the real time monitoring of the effects of exogenous small molecules on the production of metabolites and changes in pH in the large intestine. Our in vitro set-up provides an easily accessible model of the human gut that has the potential to allow detection of molecular-level changes associat-ed with disease development through inoculation with a patient’s cells or gut bacteria, as well as providing a high-throughput plat-form for drug discovery and toxicity testing.