Gut kidney axis to study the effect of antibiotics on toxin producing E.coli infection
A Very beautiful paper from Park (Sungkyunkwan U.) and Sung (Hongik U.) labs integrating intestine on a chip and kidney on a chip in one model to study the effect of two antibiotics on E. coli infection and their consequences on kidney injury. This multi-organ on a chip model not only mimics host-microbe interactions but also investigates the crosstalk between gut and kidney.
Results
In this platform, the apical side of both the gut and kidney “modules” were static, but there was a flow between the basolateral sides using rocker perfusion. The authors infected the apical side of the gut module with a strain of E. coli and studied the effect of the bacteria on the gut and kidney cells with and without two antibiotics. The antibiotics were added to the apical side of the gut section. In this platform, the E.coli-induced infection of gut cells and treatment with certain antibiotics resulted in the secretion of Shiga toxins in the gut and damage to the kidney.
Digestible of the paper Lee, Y., et al. (2021). “Gut–kidney axis on chip for studying effects of antibiotics on risk of hemolytic uremic syndrome by shiga toxin-producing escherichia coli.” Toxins 13(11): 775. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.
Method
The authors used a four-layer chip made of polycarbonate (PC), PDMS and glass, cultured Caco-2 cells on a porous membrane in the chip and cultured HKC-8 cells on a Transwell like insert that can be removed from the chip.
Fabrication: The top layer was made of (PC) using CNC machining; two middle PDMS layers were fabricated by soft lithography and the bottom layer was a glass slide
Sterilization: Autoclaving, 70% ethanol
Cell incorporation: Cells were seeded in the chip modules using a pipette
Perfusion/refreshing method: Gravity-induced perfusion by periodically tilting the chip 10 degrees (0.1 degree/s) every 10 min
On-chip read-outs: On-chip monitoring, Live-dead staining, Sensors, TEER, End-point microscopy
Strong points:
+ Simple perfusion
+ TEER measurement
+ Removable inserts
Nothing is perfect! The system can also improve:
– The same old story, PDMS but no investigation on the real concentration of the drugs
– Using cell lines
– Simulation to find out about the toxin concentration rather than real measurement
– No calculation around the volume ratios between the gut and kidney modules or between the medium and the tissues
Conclusion and outlook
Gut–kidney axis on chip of this study is designed to prevent bacterial infection in the kidney module while maintaining bacterial infection in the gut module. Therefore, it can be used to observe the harmful effects of bacterial toxins on kidney cells without the complications of bacterial infection.
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