Rotavirus used to infect most youngsters until a widely available oral vaccine came out in 2006. The virus, which causes severe diarrhea and thus life-threatening dehydration, still kills more than 450,000 kids globally every year, largely in Asia and Africa, because the vaccine is not always effective. Vanessa Harris of the University of Amsterdam wanted to find out why infants in those regions have such high rates of so-called nonresponders. Perhaps, she reasoned, the microbes that live in a child's large intestine played a role.

Harris and her colleagues, including collaborators in South Asia, studied 66 Pakistani infants and 66 matched Dutch control subjects, all of whom received the oral rotavirus vaccine. Most of the children in the Netherlands mounted the expected immune response, but only 10 of those in Pakistan did the same. A genetic scan of fecal samples taken from each infant before the vaccine revealed that the responders harbored a higher diversity of microbes in their intestinal tract. They also carried more organisms from the group Proteobacteria.

Many Proteobacteria propel themselves with the help of tail-like flagella. Those tails contain flagellin, a protein known to bolster immune cell activity. An abundance of such bacteria in the body could act as a natural immunity—and thus vaccine—booster, says Bali Pulendran, an immunologist at the Emory University School of Medicine, who was not involved in the study, which was presented in March at a Keystone Symposia meeting in Colorado.

Last year Pulendran and his colleagues demonstrated the role of flagellated bacteria in the success of the influenza vaccine. Mice living in a sterile environment that had no intestinal bacteria, as well as those inoculated with only nonflagellated bacteria, failed to raise antibodies after receiving the shot, rendering it useless. Normal mice and those inoculated with only flagellated bacteria, however, launched the typical, strong immune activity. A small follow-up human study by the team could soon reveal whether the same pattern shows up among people who have received three types of different broad-spectrum antibiotics.

Other microbial factors might also be at play. Research published in 2014 in Pediatrics showed that varying compositions of gut bacteria in Bangladeshi infants correlated with reactions to the tetanus, tuberculosis and oral polio vaccines. Taken together, these lines of research indicate that our body's native bacteria may help determine our individual immune response to vaccines. Whether the findings will eventually lead to microbiome screens or specially formulated probiotic supplements for ingestion prior to vaccination remains to be seen.

Still, a more thorough account of all the tiny organisms that live within us could help scientists make significant improvements in vaccine efficacy. And those small steps could save many thousands of lives.