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A
new study suggests that perturbations in the infant gut microbiome may
explain the greater risk of morbidity and mortality in HIV-exposed,
uninfected babies born to HIV-positive mothers. Credit: C. Bickel et
al., Science Translational Medicine (2016)
A
study led by researchers at The Saban Research Institute of Children's
Hospital Los Angeles (CHLA) suggests that maternal HIV infection
influences the microbiome of their HIV-uninfected infants. Their
findings, reported online in the journal Science Translational Medicine
on July 27, may account for some of the immunological and survival
differences seen these children.
Worldwide,
more than a million infants are born annually to HIV-infected mothers.
The vast majority of these children escape HIV infection, but do not
escape harm. These HIV exposed, uninfected children experience nearly
twice the mortality of children born to women without HIV, though the
reasons have remained unclear.
Breastfeeding
conveys health benefits to both HIV-infected and HIV-uninfected
infants. So breastfeeding - in combination with maternal antiretroviral
therapy - is the recommended form of feeding for HIV-positive mothers in
low resource settings.
The
CHLA scientists and their colleagues hypothesized that the changes in
both the microbiome and breast milk human milk oligosaccharide (HMO)
composition in HIV-infected mothers may be affecting their infants. HMOs
are the third largest constituent of human milk, but they are not
digested; rather HMOs appear to provide nutrition to the infant's
microbiome, in turn conditioning the child's developing immune system.
As
establishment of a healthy microbiome in infants greatly influences the
development of a healthy infant metabolism and immunity, it may be that
the altered microbiome of uninfected but HIV-exposed infants accounts
for their increased morbidity and mortality rates.
To
test this theory, the scientists enrolled 50 mother-and-infant pairs
from Port-au-Prince, Haiti, evenly split between HIV-positive and
HIV-negative mothers, and looked broadly at the microbiomes of sample
sites from each pair.
"In
contrast to the mostly consistent microbial communities identified in
all of the mothers, the microbiomes of HIV-exposed, uninfected infants
were strikingly different from infants born to HIV-negative women in the
same community." said first author Jeffrey M. Bender, MD, of the
Division of Infectious Diseases at Children's Hospital Los Angeles. He
added that the bacterial composition of infant stool was the most
altered on the basis of the mother's HIV status.
The
researchers observed that the bacterial communities of mothers with and
without HIV infection in the cohort were relatively similar. Therefore
the dysbiosis, or unhealthy change in the normal bacterial ecology of
the gut seen in their infants, was not completely explained by the
maternal-to-infant transfer. Instead, it appears that changes found in
the HMO content of the HIV-affected mothers' milk may have had dramatic
downstream effects on the establishment of the infants' microbiome.
"As
a result, the relatively immature and dysbiotic microbiome could
potentially compromise development of the infant's immune system," said
Bender.
The
researchers propose that it may be the combination of slight
disturbances in the HIV-infected mothers' own microbiome and differences
in the HMO composition of breast milk that may explain changes in their
infants' microbiome.
Providing
infants with important beneficial bacterial (probiotics) or potentially
specific milk oligosaccharides (called prebiotics) could potentially
improve long-term outcomes according to the scientists, though this
remains to be investigated.
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