To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by respo...

Cholera and enterotoxigenicEscherichia coli(ETEC) are among the most common causes of acute infantile gastroenteritis globally. We previously developed a rice-based vaccine that expressed cholera toxin B subunit (MucoRice-CTB) and had the advantages of being cold chain–free and providing protection against cholera toxin (CT)–induced diarrhea. To advance the development of MucoRice-CTB for human clinical application, we investigated whether the CTB-specific secretory IgA (SIgA) induced by MucoRice-CTB gives longstanding protection against diarrhea induced byVibrio choleraeand heat-labile enterotoxin (LT)–producing ETEC (LT-ETEC) in mice. Oral immunization with MucoRice-CTB stored at room temperature for more than 3 y provided effective SIgA-mediated protection against CT- or LT-induced diarrhea, but the protection was impaired in polymeric Ig receptor–deficient mice lacking SIgA. The vaccine gave longstanding protection against CT- or LT-induced diarrhea (for ≥6 months after primary immunization), and a single booster immunization extended the duration of protective immunity by at least 4 months. Furthermore, MucoRice-CTB vaccination prevented diarrhea in the event ofV. choleraeand LT-ETEC challenges. Thus, MucoRice-CTB is an effective long-term cold chain–free oral vaccine that induces CTB-specific SIgA-mediated longstanding protection againstV. cholerae– or LT-ETEC–induced diarrhea.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLDviaalteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.

Despite its direct exposure to huge amounts of microorganisms and foreign and dietary antigens, the gut mucosa maintains intestinal homeostasis by utilizing the mucosal immune system. The gut mucosal immune system protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, but it allows the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the ingenious gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. The gut mucosal immune network keeps a fine tuned balance between active immunity (against pathogens and harmful non-self antigens) and immune tolerance (to commensal microbiota and dietary antigens), thus maintaining intestinal healthy homeostasis. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review, we comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation.

Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.