Making in vitro conditions more reflective of in vivo conditions for research on the teleost gastrointestinal tract

To date, the majority of in vitro or ex vivo fish gastrointestinal research has been conducted under unrealistic conditions. In a living fish, ionic conditions, as well as levels of ammonia, pH, HCO3- and PCO2 differ considerably between the different regions of the gastrointestinal tract. These factors also differ from those of the saline often used in gut research. Furthermore, the oxygen gradient from the serosa to the gut lumen is rarely considered: in contrast to the serosa, the lumen is a hypoxic/anoxic environment. In addition, the gut microbiome plays a significant role in gut physiology, increasing the complexity of the in vivo gut, but replicating the microbial community for in vitro studies is exceptionally difficult. However, there are ways in which we can begin to overcome these challenges. Firstly, the luminal chemistry and PO2 in each gut compartment must be carefully considered. Secondly, although microbiological culture techniques are improving, we must learn how to maintain the microbiome diversity seen in vivo. Finally, for ex vivo studies, developing mucosal (luminal) solutions that more closely mimic the in vivo conditions will better replicate physiological processes. Within the field of mammalian gut physiology, great advances in 'gut-on-chip' devices are providing the tools to better replicate in vivo conditions; adopting and adapting this technology may assist in fish gut research initiatives. This Commentary aims to make fish gut physiologists aware of the various issues in replicating the in vivo conditions and identifies solutions as well as those areas that require further improvement.