Abstract
Probiotics have been recognized as vaccine adjuvants and therapeutic agents to treat acute gastroenteritis in children. We previously showed that rice bran (RB) reduced human rotavirus diarrhea in gnotobiotic pigs. Human noroviruses (HuNoVs) are the major pathogens causing non-bacterial acute gastroenteritis worldwide. In this study, Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle 1917 (EcN) were first screened for their ability to bind HuNoV P particles and virions derived from clinical samples containing HuNoV genotype GII.3 and GII.4, then the effects of LGG+EcN and RB on HuNoV infection and diarrhea were investigated using the gnotobiotic pig model. While LGG+EcN colonization inhibited HuNoV shedding, probiotic cocktail regimens in which RB feeding started 7 days prior to or 1 day after viral inoculation in the LGG+EcN colonized gnotobiotic pigs exhibited high protection against HuNoV diarrhea and shedding, characterized by significantly reduced incidence (89 versus 20%) and shorter mean duration of diarrhea (2.2 versus 0.2 days), as well as shorter mean duration of virus shedding (3.2 versus 1.0 days). In both probiotic cocktail groups, the diarrhea reduction rates were 78% compared with the control group, and diarrhea severity was reduced as demonstrated by the significantly lower cumulative fecal scores. The high protective efficacy of the probiotic cocktail regimens was attributed to stimulation of IFN-γ+ T cell responses, increased production of intestinal IgA and IgG, and maintenance of healthy intestinal morphology (manifested as longer villi compared with the control group). Therefore, probiotic cocktail regimens containing LGG+EcN and RB may represent highly efficacious strategies to prevent and treat HuNoV gastroenteritis, and potentially other human enteric pathogens.
Highlights
Human noroviruses, non-enveloped viruses with a positivestrand RNA genome, are the major pathogens causing nonbacterial acute gastroenteritis worldwide (Pringle et al, 2015)
P particles were first used as a model to determine human norovirus (HuNoV) interactions with probiotics, including a Gram-negative strain Escherichia coli Nissle 1917 (EcN) and four Gram-positive lactobacilli strains, i.e., L. reuteri (LR), L. acidophilus (LA), L. rhamnosus GG (LGG), and L. bulgaricus (LB)
Since Enterobacter cloacae (EC) can bind to HuNoVs by surface histo-blood group antigen (HBGA) (Miura et al, 2013), native EC was used as a positive control and HBGA A&H antibodies-blocked EC was a negative control in the binding assays
Summary
Non-enveloped viruses with a positivestrand RNA genome, are the major pathogens causing nonbacterial acute gastroenteritis worldwide (Pringle et al, 2015). In the United States, HuNoVs have replaced HRVs as the single most common cause of viral gastroenteritis in children and adults (Bresee et al, 2012; Payne et al, 2013). Promising vaccines have focused on recombinant capsid proteins, including VLPs and P particles (Kocher and Yuan, 2015). Neonatal gnotobiotic (Gn) pigs recapitulate the pathologic hallmarks of enteric viral infection and associated immune responses in the gastrointestinal tract of young children (Yang and Yuan, 2014). As the only animal model that supports the oral route of HuNoV infection, develops diarrhea, and sheds virus in feces, Gn pigs are used to evaluate viral pathogenesis and vaccine efficacy with high translational validity to humans (Cheetham et al, 2006; Bui et al, 2013; Kocher et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
