title: Stool microbiota and vaccine responses of infants.
abstract: OBJECTIVE
  Oral vaccine efficacy is low in less-developed countries, perhaps due to intestinal dysbiosis. This study determined if stool microbiota composition predicted infant oral and parenteral vaccine responses.
  
  
  METHODS
  The stool microbiota of 48 Bangladeshi infants was characterized at 6, 11, and 15 weeks of age by amplification and sequencing of the 16S ribosomal RNA gene V4 region and by Bifidobacterium-specific, quantitative polymerase chain reaction. Responses to oral polio virus (OPV), bacille Calmette-Guérin (BCG), tetanus toxoid (TT), and hepatitis B virus vaccines were measured at 15 weeks by using vaccine-specific T-cell proliferation for all vaccines, the delayed-type hypersensitivity skin-test response for BCG, and immunoglobulin G responses using the antibody in lymphocyte supernatant method for OPV, TT, and hepatitis B virus. Thymic index (TI) was measured by ultrasound.
  
  
  RESULTS
  Actinobacteria (predominantly Bifidobacterium longum subspecies infantis) dominated the stool microbiota, with Proteobacteria and Bacteroidetes increasing by 15 weeks. Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales, Pseudomonadales, and Clostridiales were associated with neutrophilia and lower vaccine responses.
  
  
  CONCLUSIONS
  Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses. Vaccine responsiveness may be improved by promoting intestinal bifidobacteria and minimizing dysbiosis early in infancy.
authors.affiliation: US Department of Agriculture Western Human Nutrition Research Center, Davis California;International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; and.
authors.forename: M Nazmul
authors.initials: MN
authors.lastname: Huda
authors.affiliation: Departments of Viticulture and Enology, and.
authors.forename: Zachery
authors.initials: Z
authors.lastname: Lewis
authors.affiliation: Departments of Viticulture and Enology, and.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kalanetra
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; and.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; and.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Ahmad
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; and.
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; and.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Pediatrics, University of California, Davis, Davis, California.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Underwood
authors.affiliation: Departments of Viticulture and Enology, and.
authors.forename: David A
authors.initials: DA
authors.lastname: Mills
authors.affiliation: US Department of Agriculture Western Human Nutrition Research Center, Davis California; charles.stephensen@ars.usda.gov.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stephensen
mesh_terms: D039903:Actinobacteria / Q000302:isolation & purification*; D001500:BCG Vaccine / Q000276:immunology / Q000627:therapeutic use; D001644:Bifidobacterium / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000302:isolation & purification; D064806:Dysbiosis / Q000276:immunology*; D004755:Enterobacteriaceae / Q000276:immunology; D005243:Feces / Q000382:microbiology*; D005260:Female; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008828:Microbiological Techniques; D064307:Microbiota / Q000276:immunology*; D009752:Nutritional Status; D011055:Poliovirus Vaccine, Oral / Q000276:immunology; D011549:Pseudomonas / Q000276:immunology; D012336:RNA, Ribosomal, 16S; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000627:therapeutic use; D013950:Thymus Gland / Q000276:immunology; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D001500:BCG Vaccine; D004269:DNA, Bacterial; D017325:Hepatitis B Vaccines; D011055:Poliovirus Vaccine, Oral; D012336:RNA, Ribosomal, 16S; D013745:Tetanus Toxoid; D014612:Vaccines
keywords: Actinobacteria; Bangladesh; Bifidobacterium; Proteobacteria; T lymphocyte; antibody; hepatitis; intestinal; microbiota; polio; tetanus; tuberculosis; vaccine