Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and Tcells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.

The earliest autoantibodies in lupus are directed against the RNA binding autoantigen Ro60, but the triggers against this evolutionarily conserved antigen remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and gut commensal bacterial species and confirmed the presence of these orthologs in patients with lupus and healthy controls. Thus, we hypothesized that commensal Ro60 orthologs may trigger autoimmunity via cross- reactivity in genetically susceptible individuals. Sera from human anti-Ro60–positive lupus patients immunoprecipi-tated commensal Ro60 ribonucleoproteins. Human Ro60 autoantigen–specific CD4 memory T cell clones from lupus patients were activated by skin and mucosal Ro60-containing bacteria, supporting T cell cross-reactivity in humans. Further, germ-free mice spontaneously initiated anti-human Ro60 T and B cell responses and developed glomerular immune complex deposits after monocolonization with a Ro60 ortholog–containing gut commensal, linking anti- Ro60 commensal responses in vivo with the production of human Ro60 autoantibodies and signs of autoimmunity. Together, these data support that colonization with autoantigen ortholog-producing commensal species may initiate and sustain chronic autoimmunity in genetically predisposed individuals. The concept of commensal ortholog cross-reactivity may apply more broadly to autoimmune diseases and lead to novel treatment approaches aimed at defined commensal species.

The use of novel nanostructured materials has attracted considerable interest in the food industry for their utilization as highly functional ingredients, high-performance packaging materials, processing aids, and food quality and safety sensors. Most previous application interest has focused on the development of nanoparticles. However, more recently, the ability to produce non-woven mats composed of nanofibers that can be used in food applications is beginning to be investigated. Electrospinning is a novel fabrication technique that can be used to produce fibers with diameters below 100 nm from (bio-) polymer solutions. These nanofibers have been shown to possess unique properties that distinguish them from non-woven fibers produced by other methods, e.g., melt-blowing. This is because first the process involved results in a high orientation of polymers within the fibers that leads to mechanically superior properties, e.g., increased tensile strengths. Second, during the spinning of the fibers from polymer solutions, the solvent is rapidly evaporated allowing the production of fibers composed of polymer blends that would typically phase separate if spun with other processes. Third, the small dimensions of the fibers lead to very high specific surface areas. Because of this the fiber properties may be greatly influenced by surface properties giving rise to fiber functionalities not found in fibers of larger sizes. For food applications, the fibers may find uses as ingredients if they are composed solely of edible polymers and GRAS ingredients, (e.g., fibers could contain functional ingredients such as nutraceuticals, antioxidants, antimicrobials, and flavors), as active packaging materials or as processing aids (e.g., catalytic reactors, membranes, filters (Lala et al., 2007), and sensors (Manesh et al., 2007; Ren et al., 2006; Sawicka et al., 2005). This review is therefore intended to introduce interested food and agricultural scientists to the concept of nano-fiber manufacturing with a particular emphasis on the use of biopolymers. We will review typical fabrication set-ups, discuss the influence of process conditions on nanofiber properties, and then review previous studies that describe the production of biopolymer-based nanofibers. Finally we briefly discuss emerging methods to further functionalize fibers and discuss potential applications in the area of food science and technology.

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The purpose of this study was to evaluate down-regulation of tumor necrosis factor (TNF)-α by oral RNA interference therapy. Control (scrambled sequence) or TNF-α specific small interfering RNA (siRNA) was encapsulated in type B gelatin nanoparticles and further entrapped in poly(epsilon-caprolactone) (PCL) microspheres to form a nanoparticles-in-microsphere oral system (NiMOS). Upon confirmation of the dextran sulfate sodium (DSS)-induced acute colitis model, mice were divided into several treatment groups receiving no treatment, blank NiMOS, NiMOS with scramble siRNA, or NiMOS with TNF-α silencing siRNA by oral administration. Successful gene silencing led to decreased colonic levels of TNF-α, suppressed expression of other pro-inflammatory cytokines (e.g., interleukin (IL)-1β, interferon (IFN)-γ) and chemokines (MCP-1), an increase in body weight, and reduced tissue myeloperoxidase activity. Results of this study established the clinical potential of a NiMOS-based oral TNF-α gene silencing system for the treatment of inflammatory bowel disease as demonstrated in an acute colitis model.

Highlights d Core epitopes of the APS autoantigen b 2 GPI are conserved in R. int d Human b 2 GPI-specific Th1 cell clones and autoantibodies cross-react with R. int mimotopes d Mimotope-dependent anti-R. int titers correlate with antib 2 GPI titers in APS patients d Gavage of (NZW 3 BXSB)F 1 mice with R. int induces antib 2 GPI IgG and APS-like pathology Authors