Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana.
BACKGROUND
Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings.


METHODS
We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip.


RESULTS
We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009).


CONCLUSIONS
The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
Amsterdam Institute for Global Health and Development.|Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam.
Vanessa C
VC
Harris
Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon.
George
G
Armah
Laboratory of Microbiology, Wageningen University.
Susana
S
Fuentes
Department of Bacteriology and Immunology, and Immunobiology, University of Helsinki, Finland.
Katri E
KE
Korpela
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Center for Disease Control and Prevention, Atlanta, Georgia.
Umesh
U
Parashar
PATH, Vaccine Access and Delivery, Seattle, Washington.
John C
JC
Victor
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Center for Disease Control and Prevention, Atlanta, Georgia.
Jacqueline
J
Tate
Behavioral Science Institute, Radboud University, Nijmegen, The Netherlands.
Carolina
C
de Weerth
Department of Paediatrics, University of Padova, Italy.
Carlo
C
Giaquinto
Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam.
Willem Joost
WJ
Wiersinga
Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam.
Kristen D C
KD
Lewis
Laboratory of Microbiology, Wageningen University.|Department of Bacteriology and Immunology, and Immunobiology, University of Helsinki, Finland.
Willem M
WM
de Vos
D000914:Antibodies, Viral / Q000097:blood; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D041963:Bacteroidetes / Q000302:isolation & purification; D016022:Case-Control Studies; D005243:Feces / Q000382:microbiology; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D008297:Male; D046228:Microarray Analysis; D011247:Pregnancy; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012424:Rural Population / Q000706:statistics & numerical data; D016985:Streptococcus bovis / Q000302:isolation & purification; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
intestinal microbiome; mucosal immunity; rotavirus vaccine