Germ-free, or GF, animals are laboratory animals that completely lack microbes, making them useful tools for microbiome research. Researchers create GF animals in laboratories by delivering the newborn animals in a way that protects them from microbes, which are microscopic organisms such as bacteria and viruses. They then house the GF animals in sterile conditions to ensure that the animals stay germ free. The creation of GF animals began in the late nineteenth century. Prior to that, scientists had no way to study the effects of the microbiome on overall health. The creation of GF animals allowed researchers to examine the microbiome under controlled conditions. They could colonize the animal with specific microbes and study their effects on the animal’s health without the confounding presence of other microbes. Researchers have used GF animals as a living model to study the microbiome, which has provided evidence for a relationship between the microbiome and health, including a role for the microbiome in shaping the development of multiple body systems.

In 2016, researcher Thomas Gensollen and colleagues published “How Colonization by Microbiota in Early Life Shapes the Immune System,” hereafter, “Microbiota Shapes the Immune System,” in Science. The article reviews [what is known about?] how microbial colonization impacts immune development in newborns. Because the immune system protects the body from infection, an individual’s microbiome composition also affects susceptibility to certain diseases. Specifically, the authors discuss microbe colonization during early life, a time they refer to as the window of opportunity for future disease susceptibility. That window of opportunity is a period where environmental influences more easily shape the infant’s immune cells and their functions. In turn, the authors present that window as an optimal time for treating disorders associated with the microbiome and the immune system. “Microbiota Shapes the Immune System” reviewed data from dozens of articles to show that there is a narrow window during infancy where microbiome interactions directly or indirectly influence immune development, a potential area for interventional methods to target immune development.

In 2021, Brooke Wilson and colleagues published “Oral Administration of Maternal Vaginal Microbes at Birth to Restore Gut Microbiome Development in Infants Born by Caesarean Section: A Pilot Randomised Placebo-controlled Trial,” hereafter “Oral Administration,” in eBiomedicine. Previous researchers had established that neonates born via caesarean section, or c-section, the surgical delivery of an infant through an incision made in the mother’s abdomen, have different gut microbiomes from neonates delivered vaginally. They further hypothesized that such a difference may be because infants born by c-section do not receive exposure to their mother’s vaginal microbiome during delivery. Thus, Wilson and colleagues investigate whether oral vaginal seeding, or the process of transferring vaginal microbes to a newborn’s mouth, can restore the gut microbiome of newborns born by c-section. “Oral Administration” was one of the first articles to demonstrate that oral vaginal seeding is ineffective in altering the gut microbiome of newborns delivered by c-section and prompted other researchers to explore alternative research routes to enhancing the gut microbiome of newborns born by c-section.

In 2010, Maria Dominguez-Bello, Elizabeth Costello, Monica Contreras, and colleagues published “Delivery Mode Shapes the Acquisition and Structure of the Initial Microbiota Across Multiple Body Habitats in Newborns,” hereafter “Delivery Mode” in the journal Proceedings of the National Academy of Sciences. The term microbiota, which the authors use interchangeably with the term microbiome, refers to the collection of microorganisms, including bacteria, fungi, and viruses, found in and on the human body. The development of the microbiome, which begins at birth when a newborn is first exposed to the mother’s microbiota, impacts the development of the immune system, and how a person’s body responds to disease. Though researchers in the early 2000s were aware of a connection between delivery mode and the neonatal gut microbiome, they knew little about how delivery mode affects a neonate’s microbiome beyond the gut. Dominguez-Bello and associates’ experiment was one of the first to show that a neonate’s microbial community is uniform across their body and elaborate on the differences in microbiomes across delivery methods, which can make neonates born via c-section more susceptible to conditions such as asthma.

The Vaginal Microbiome Consortium, or the VMC, established in 2007, consists of a group of researchers, clinicians, statisticians, and geneticists who study the impact of the vaginal microbiome on women’s health. Virginia Commonwealth University in Richmond, Virginia operates the VMC. The United States National Institutes of Health, or the NIH, funds the VMC’s ongoing project called the Vaginal Microbiome Project. Thousands of women have contributed samples for use in research studies by the VMC, which its members have used to research the communities of microorganisms that live in the vagina. A balanced vaginal microbiome can decrease the risk of preterm birth and sexually transmitted infections, or STIs, and pelvic diseases, which helps support women’s health. Researchers can use the VMC’s findings to develop genetic sequence testing for pregnant women to predict preterm birth, which accounted for 10.4 percent of live births in the United States in 2023. The VMC’s research in reproductive health has allowed physicians to prepare birth and treatment plans that improve maternal and infant health and survival.