Vitamin A, Stool Microbiota and Vaccine Response in Bangladeshi Infants

Vitamin A deficiency (VAD) increases the risk of death from infections in infants and young
children. The World Health Organization (WHO) recommends high-dose vitamin A supplementation
(VAS) from 6-59 months of age to reduce the risk of death in countries where VAD is common.
Such countries include Bangladesh, where this study is being conducted. While providing VAS
at 6 months is recommended, providing VAS at birth may also decrease the risk of death since
newborn infants are also at risk of VAD. VAS presumably reduces infant mortality by
improving the immune response to infection and immunization. Vitamin A particularly affects
the development and function of T cells, which develop in the thymus and are a key component
of the memory response to infection and immunization. Vitamin A is important for development
of an important class of T cells, regulatory T-cells, in the intestine. Regulatory T-cells
prevent over-reaction of the immune system to substances the immune system might otherwise
treat as harmful such as food or the healthy bacteria in the intestine. VAD could disrupt
the normal colonization of the infant's intestinal tract and cause a condition called
"dysbiosis" where abnormal bacteria flourish and adversely affect the infant's immune
system. Dysbiosis may disrupt the immune response to injectable and oral vaccines. VAS at
birth may prevent dysbiosis and thus improve immune function, response to vaccines, and
child survival. The investigators recently completed an intervention trial in Bangladeshi
infants (NCT01583972) examining the effect of VAS at birth on immune function and response
to vaccines administered from birth to 14 wk of age. The present study will recruit infants
who completed NCT01583972 when they are from 12 to 24 m of age to determine if VAS at birth
affects the responses to these same vaccines when they are measured during the second year
of life. The investigators will examine the effect of VAS at birth on gut microbiota
measured early in infancy and during the second year of life, and explore the association of
the gut microbiota with vaccine response. Mothers of study infants will participate in the
study because the breast milk oligosaccharide content strongly affects gut microbiota
composition and the "secretor status" of the mother, which can be determined from maternal
FUT2 genotype, strongly affects breast milk oligosaccharide content.