HIV infection in mothers can disrupt the development of the gut microbiome of HIV-exposed but uninfected babies, potentially explaining why these infants are more vulnerable to death and disease, researchers report in a new study. Conducted in 50 Haitian mother and infant pairs, the study links microbiome perturbations in these infants to changes in the composition of the HIV-positive mother's breast milk. The findings could open the door to treating these at-risk babies with probiotics or prebiotics to help ensure normal microbiome development. Each year, more than a million HIV-exposed, uninfected infants are born to HIV-positive mothers worldwide, and the number of these infants continues to grow. Even as antiretroviral therapies are successfully preventing mother-to-child transmission of HIV, HIV-exposed but uninfected babies are at greater risk of morbidity and at nearly twice the risk of mortality than unexposed, uninfected infants. The reasons behind this poorer health have remained elusive. Suspecting the gut microbiome as a potential culprit, Jeffrey Bender and colleagues compared the microbiomes of 50 Haitian babies and their mothers, half of whom were HIV-positive and the other half HIV-negative. Although the gut microbiota of infected and uninfected mothers was largely similar, the researchers detected striking differences in that of their respective children. The gut microbiomes of HIV-exposed, uninfected infants were less diverse and less mature, and displayed altered composition of the bacterial community. Furthermore, the oligosaccharide composition of breast milk, one of the key routes by which moms pass bacteria to their babies, differed between HIV-infected and uninfected mothers. Oligosaccharides, indigestible carbohydrates in milk, are thought to serve as a prebiotic that promotes the growth of "good" gut bacteria. Altogether, the findings suggest that preventing perturbations in the infant gut microbiome may offer a potential avenue for improving the health of HIV-exposed, uninfected babies.