Abstract
BackgroundRecurrence of hand, foot and mouth disease (HFMD) pandemics continues to threaten public health. Despite increasing awareness and efforts, effective vaccine and drug treatment have yet to be available. Probiotics have gained recognition in the field of healthcare worldwide, and have been extensively prescribed to babies and young children to relieve gastrointestinal (GI) disturbances and diseases, associated or not with microbial infections. Since the faecal-oral axis represents the major route of HFMD transmission, transient persistence of probiotic bacteria in the GI tract may confer some protection against HFMD and limit transmission among children.MethodsIn this work, the antiviral activity of two commercially available probiotics, namely Lactobacillus reuteri Protectis (L. reuteri Protectis) and Lactobacillus casei Shirota (L. casei Shirota), was assayed against Coxsackieviruses and Enterovirus 71 (EV71), the main agents responsible for HFMD. In vitro infection set-ups using human skeletal muscle and colon cell lines were designed to assess the antiviral effect of the probiotic bacteria during entry and post-entry steps of the infection cycle.ResultsOur findings indicate that L. reuteri Protectis displays a significant dose-dependent antiviral activity against Coxsackievirus type A (CA) strain 6 (CA6), CA16 and EV71, but not against Coxsackievirus type B strain 2. Our data support that the antiviral effect is likely achieved through direct physical interaction between bacteria and virus particles, which impairs virus entry into its mammalian host cell. In contrast, no significant antiviral effect was observed with L. casei Shirota.ConclusionsShould the antiviral activity of L. reuteri Protectis observed in vitro be translated in vivo, such probiotics-based therapeutic approach may have the potential to address the urgent need for a safe and effective means to protect against HFMD and limit its transmission among children.
Highlights
Recurrence of hand, foot and mouth disease (HFMD) pandemics continues to threaten public health
Live L. reuteri Protectis bacteria significantly reduced CA6, CA16, enterovirus 71 (EV71) but not coxsackievirus type B strain 2 (CB2) virus titers in infected RD and Caco-2 cells Prior to evaluating the antiviral activity of L. reuteri Protectis bacteria in human RD and intestinal Caco-2 cell lines, a cell viability assay was performed to assess the cytotoxicity of these probiotic bacteria
Results indicated that 1 h incubation of up to 1011 CFU of live L. reuteri Protectis bacteria with RD and Caco-2 cell monolayers did not lead to significant cell viability loss (≥80 % viability) (Fig. 1)
Summary
Recurrence of hand, foot and mouth disease (HFMD) pandemics continues to threaten public health. Foot and mouth disease (HFMD) is a common viral infection that affects mostly infants and children below 5 years of age. The main causative agents responsible for HFMD belong to a group of enteroviruses from Picornaviridae family, and consist predominantly of coxsackievirus type A (CA) strain 16 (CA16) and enterovirus 71 (EV71) [1]. Other enteroviruses such as CA6, CA7, CA10, CA14 and coxsackievirus type B strain 2 (CB2) may associate with the disease. The disease is mild and self-limiting, with major clinical features manifesting as HFMD and herpangina [2, 3]. A growing body of evidence suggests that overwhelming production of inflammatory mediators associated with high viral titer plays a critical role in the pathogenesis of EV71 infection [3, 6, 7]
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