Escherichia coli Nissle 1917 colonization ameliorates human rotavirus diarrhea and modulates B cell responses in a neonatal gnotobiotic pig disease model (VIR7P.1064)

Abstract

Abstract Microbiota regulate gut immune homeostasis, but the role of gram positive (G+)/negative (G-) commensals/probiotics in modulating human rotavirus (HRV) diarrhea and immunity is largely undefined. Gnotobiotic (Gn) piglets, the only animal model susceptible to HRV diarrhea, were colonized with G- Escherichia coli Nissle 1917 (EcN), G+ Lactobacillus rhamnosus strain GG (LGG) or LGG+EcN and challenged with virulent HRV (VirHRV) to assess probiotic effects on HRV pathogenesis and immunity. EcN+VirHRV piglets had significantly lower mean peak virus shedding titers and significantly reduced mean cumulative fecal scores and duration of diarrhea compared to LGG+VirHRV or control (uncolonized)+VirHRV piglets. LGG+VirHRV pigs had lower, but statistically similar fecal scores compared to control+VirHRV pigs. Combining LGG+EcN did not moderate VirHRV shedding or diarrhea more than EcN alone. Coinciding with reduced HRV infection, EcN+VirHRV piglets had significantly lower small intestinal (SI) HRV IgA antibody titers and HRV IgA and IgG antibody secreting cells (SC) compared to control+VirHRV piglets. Though not significantly different, SI HRV IgA antibody titers were 2-4-fold lower in the LGG+EcN+VirHRV and LGG+VirHRV piglets. Notably EcN+VirHRV piglets had higher SI total IgA levels and IgA SC compared to LGG+VirHRV piglets. Our results indicate that EcN alone was more effective than LGG or LGG+EcN in ameliorating HRV diarrhea and modulating B cell responses in a Gn piglet disease model.