Association Between Maternal Breastmilk Microbiota Composition and Rotavirus Vaccine Response in African, Asian, and European Infants: A Prospective Cohort Study

Abstract Background Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence...

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Published inThe Journal of infectious diseases Vol. 228; no. 5; pp. 637 - 645
Main Authors Mandolo, Jonathan, Parker, Edward P K, Bronowski, Christina, Sindhu, Kulandaipalayam Natarajan C, Darby, Alistair C, Cunliffe, Nigel A, Kang, Gagandeep, Iturriza-Gómara, Miren, Kamng’ona, Arox W, Jere, Khuzwayo C
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 31.08.2023
Subjects
Antibodies, Viral
Female
Humans
Immunogenicity
Immunoglobulin A
Infant
Infant, Newborn
Infants
Intestinal microflora
Major
Microbiota
Microorganisms
Milk, Human
Neonates
Prospective Studies
Rotavirus
Rotavirus Infections - epidemiology
Rotavirus Infections - prevention & control
Rotavirus Vaccines
Seroconversion
Vaccines
Vaccines, Attenuated
Viruses
United Kingdom > UK
Malawi
India
microbiota
breastmilk
rotavirus
immunogenicity
Online AccessGet full text
ISSN0022-1899
1537-6613
1537-6613
DOI10.1093/infdis/jiad234

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Summary:Abstract Background Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity. Methods Using standardized methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the United Kingdom ([UK] n = 60). Results Breastmilk microbiota diversity was higher in India and Malawi than the UK across 3 longitudinal samples spanning weeks of life 1 to 13. Dominant taxa such as Streptococcus and Staphylococcus were consistent across cohorts; however, significant geographic differences were observed in the prevalence and abundance of common and rare genera throughout follow up. No consistent associations were identified between breastmilk microbiota composition and ORV outcomes including seroconversion, vaccine shedding after dose 1, and postvaccination rotavirus-specific immunoglobulin A level. Conclusions Our findings suggest that breastmilk microbiota composition may not be a key factor in shaping trends in ORV response within or between countries. Breastmilk microbiota composition differed significantly between cohorts in India, Malawi, and the UK. No consistent associations were identified between breastmilk microbiota composition and infant oral rotavirus vaccine response.
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G. K., M. I.-G., A.W. K., and K. C. J. jointly supervised this work.
J. M. and E. P. K. P. contributed equally to this work.
Other members of the RoVI study group: Sudhir Babji, Blossom Benny, Noelia Carmona-Vicente, Nedson Chasweka, End Chinyama, Queen Dube, Sidhartha Giri, Nicholas C. Grassly, Annai Gunasekaran, Deborah Howarth, Sushil Immanuel, Jenna Lowe, Ira Praharaj, Bakthavatsalam Sandya Rani, Sophia Silas, Vivek Kumar Srinivasan, Mark Turner, Srinivasan Venugopal, Valsan Philip Verghese.
Potential conflicts of interest. NAC is a NIHR Senior Investigator (NIHR203756). NAC and KCJ are affiliated with the NIHR Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool, a partnership with the UKHSA, in collaboration with the University of Warwick. MI-G has received research grants from GSK and Merck and has provided expert advice to GSK. MI-G has been an employee of GSK since January 2023, although the work presented here was completed before this date. KCJ has received investigator-initiated research grant support from GSK. NAC has served on a rotavirus vaccine Data Safety Monitoring Board for GSK and has served on a rotavirus vaccine Scientific Advisory Board for Sanofi Pasteur. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Presented in part: 14th International dsRNA Virus Symposium 2022, October 10–14, 2022, Banff, Alberta, Canada; 1st Kamuzu University of Health (KUHeS) Research Dissemination Conference, November 24–25, 2022, Blantyre, Malawi.
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiad234