When a baby is born, so too is a new microbial ecosystem in the baby's gut. The Stanford team has made the most extensive survey yet of how the microbes establish flourishing communities in what began as a sterile environment. Their findings will be published in the July issue of Public Library of Science-Biology.
Researchers at the Stanford University School of Medicine are as interested in a baby's poop as doting parents are, and for good reason.
"It's an amazing thing trying to figure out how we go from a completely sterile gut to having a microbial ecosystem that will be with us for the rest of our lives," said the study's senior author, Patrick Brown, MD, PhD, professor of biochemistry. "What could be more fundamental than that.
Looking at stool samples from 14 healthy, full-term infants over their first year of life, including one set of fraternal twins, the researchers found that each baby had very different microbes colonizing their intestinal tracts at different stages.
"This study emphasizes that the definition of a 'healthy' baby is pretty broad," said the article's lead author Chana Palmer, PhD, who was a graduate student in Brown's lab at the time the work was done. She noted that by the end of the first year, despite the chaos of the early months, each baby's intestinal ecology remained unique but harbored dynamic, complex societies of microbes similar to that found in adults' intestines.
The gut of a baby is a rapidly evolving place. It has no inhabitants before birth. Within days of an infant's delivery, the microbial immigrants in the gut establish a thriving community whose population soon outnumbers that of the baby's own cells tenfold, a ratio that persists throughout life.
"It's really striking the degree to which the patterns of bacterial abundance were so dynamic over time," said David Relman, MD, a collaborator on the work. "Things appear and then things suddenly drop in abundance and other things appear and take their place." There are no obvious reasons for these fluctuations, but there must be important factors underlying these patterns, said Relman, associate professor of medicine and of microbiology and immunology.
Six of the 14 babies had some course of antimicrobial medicine during their first year. Only one of the babies had an extremely dramatic change in the microbial community in response to the drugs. "But it was so dramatic it makes us want to look at more examples of that and try to understand generalizations of the process," Palmer said.
The researchers had one set of fraternal twins in their study, the only babies delivered by a planned caesarean section and thus without any exposure to the mother's vaginal or rectal environments. They had much lower bacterial levels than the other babies for the first week of life.
The twins also showed the most similarity in their microbial community profiles, leading to speculation that combinations of genetics and environment can shape a microbial community. "The fact that the twins were so similar gives us a glimmer of hope that it's not a completely chaotic process," said Palmer.
Although microbes' reputation for causing disease usually gets top billing, the tiny critters play a number of critical roles in health, including processing nutrients, defining host body-fat content and providing protection against invading pathogens.
Despite their significant role in health, much of their existence remains a mystery. No more than half the total number of intestinal-tract organisms are even recognized, Relman said.
This study relied heavily on the use of a DNA microarray - technology that Brown helped develop in the mid-1990s. It consists of a glass microscope slide with an orderly array of DNA spots that can give a snapshot of genetic activity in a given sample.
The microarray design for this study included spots representing nearly all bacteria known to be involved in human microbial ecosystems. The researchers included spots that would recognize whole families of bacteria so that they wouldn't be limited to the 80,000 or so known species.
The researchers had the parents collect stool samples from the babies according to a prescribed schedule, beginning with the first stool produced after birth. There were additional samples around key events, such as starting on solid food and taking antibiotics.
Postdoctoral scholar Elisabeth Bik, PhD, and research fellow Daniel DiGiulio, MD, in Relman's lab, were involved in processing and analyzing more than 500 samples in this study.
The team emphasized that the goal of this study was to provide the foundation for the range of what occurs in healthy babies born to healthy mothers. Based on this, future studies may find new species of bacteria, and also separate the role that genetics plays compared with life history and identify new roles of microbes in human health.
Other factors for future inquiry include looking at breast-fed babies compared to those who are formula-fed, and comparing premature babies to full-term ones. All the babies in this study were full-term and breast-fed.
"This study raises so many interesting questions, and it's a wonderful segue into the next phase," said Relman.
This work was supported by funding from the Horn Foundation, the National Institutes of Health and the Howard Hughes Medical Institute. Brown is an investigator for the Howard Hughes Medical Institute.