Anti-rotavirus Properties and Mechanisms of Selected Gram-Positive and Gram-Negative Probiotics on Polarized Human Colonic (HT-29) Cells.

Abstract

Probiotics have been investigated to improve the universal rotavirus (RV) vaccination as well as to ameliorate the RV infection. However, underlying mechanisms how probiotics mediate beneficial effects needs more investigation. Thus, in the present study, we used polarized HT-29 cells to assess the anti-RV properties of Gram-positive, (Lactobacillus acidophilus, Lacticaseibacillus rhamnosus GG, and Bifidobacterium subsp. Lactis Bb12) and Gram negative, (Escherichia coli Nissle 1917) probiotics and study their underlying mechanisms. Our results showed that pre-treatment of HT-29 cells for 4h with probiotics, significantly reduced (p < 0.05) human RV replication and this effect was most pronounced for E. coli Nissle followed by L. acidophilus and L. rhamnosus GG. Strikingly, only pre-treatment with live bacteria or their supernatants demonstrated anti-RV properties. Except Gram negative E. coli Nissle, the Gram-positive probiotics tested did not bind to RV. Ingenuity pathway analysis of tight junction (TJ)- and innate immune-associated genes indicated that E. coli Nissle or E. coli Nissle + RV treatments improved cell-cell adhesion and cell contact, while L. acidophilus or L. acidophilus + RV treatments also activated cell-cell contact but inhibited cell movement functions. RV alone inhibited migration of cells event. Additionally, E. coli Nissle activated pathways such as the innate immune and inflammatory responses via production of TNF, while RV infection activated NK cells and inflammatory responses. In conclusion, E. coli Nissle's ability to bind RV, modulate expression of TJ events, innate immune and inflammatory responses, via specific upstream regulators may explain superior anti-RV properties of E. coli Nissle. Therefore, prophylactic use of E. coli Nissle might help to reduce the RV disease burden in infants in endemic areas.