title: Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity.
abstract: BACKGROUND
  Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences.
  
  
  METHODS
  The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay.
  
  
  RESULTS
  Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin A-producing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies.
  
  
  CONCLUSIONS
  Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions.
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, Georgia.
authors.forename: Robin
authors.initials: R
authors.lastname: Uchiyama
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University.
authors.forename: Benyue
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, Georgia.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood*; D003967:Diarrhea / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D041981:Gastrointestinal Tract / Q000821:virology; D056724:Immunity, Humoral; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012401:Rotavirus / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019562:Viral Load
chemical_list: D000900:Anti-Bacterial Agents; D000914:Antibodies, Viral
keywords: antibiotics; germ-free; microbiota; mucosal immunity; vaccine