| Summary: | Recent research has indicated that dysbiosis of the gut microbiota can lead to an altered circadian clock of the mammalian host. Herein we developed an original system that allows real-time circadian studies of human HepG2 hepatoma cells co-cultured with bacteria. The HepG2 cells with stably integrated firefly luciferase reporter under the control of <i>PERIOD2</i> promoter were co-cultured with <i>E. coli</i> strains isolated from human fecal samples from healthy individuals. The two <i>E. coli</i> strains differ in the phylogenetic group and the number of ExPEC virulence-associated genes: BJ17 has only two, and BJ23 has 15 of 23 tested. In the first 24 h, the <i>E. coli</i> BJ17 affected the HepG2 circadian clock more than BJ23. Cosinor analysis shows a statistically significant change in the amplitude of <i>PER1</i> and <i>2</i> and the phase advance of <i>PER3.</i> A high percentage of necrotic and apoptotic cells occurred at 72 h, while a correlation between the number of ExPEC genes and the influence on the HepG2 core clock gene expression was observed. Our study reveals that the <i>E. coli</i> genetic background is important for the effect on the mammalian circadian clock genes, indicating possible future use of probiotic <i>E. coli</i> strains to influence the host circadian clock.
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